Mexico has reported a new human case of H5 avian influenza in a 23-year-old woman in Mexico City, according to health officials. The patient has since been released from the hospital. The woman, who had no recent history of travel, began developing symptoms on September 14, according to the Pan American Health Organization (PAHO). She was later admitted to a hospital in the country’s capital. Her illness began with respiratory symptoms, including a runny nose and cough, which progressed to fever, painful swallowing, and later hemoptysis (coughing up blood) and chest pain. A sample collected on September 29 tested positive for unsubtypeable influenza A, and the presence of influenza A(H5) was confirmed by real-time RT-PCR the following day, PAHO said. She was treated with oseltamivir and discharged on October 11.   Health authorities said a dog lived at the woman’s residence, and several birds were present in the building’s courtyard, including a poultry bird and two pigeons. Bird droppings were also found in multiple areas, including a poorly sealed cistern that supplied water to all apartments in the building. Samples collected from the animals tested positive for influenza A(H5), while environmental samples are still being analyzed. Tests from 41 identified contacts of the patient were all negative for the virus, according to officials. It remains unclear which H5 subtype caused the infection. Mexico’s first reported human case of avian influenza occurred in 2024 and involved the H5N2 strain, which led to the death of a 59-year-old man in the neighboring State of Mexico. Earlier this year, the country reported its first H5N1 case, a 3-year-old girl from a rural area in northern Mexico who died after severe complications. Genetic analysis identified the strain as Genotype D1.1. This genotype has also been detected in at least five human cases across North America, including the fatal case of a person in Louisiana in 2024, the first confirmed H5N1 death in the United States. It also caused severe illness in a teenager in Canada and in an adult in Wyoming in February.   The spread of H5N1 clade 2.3.4.4b and its multiple genotypes has raised concern among global health experts due to its wide geographic distribution and ability to infect both birds and mammals. Since 2022, at least 92 human infections with this clade have been reported worldwide, most linked to contact with infected poultry or dairy cattle.  

Background Ensitrelvir is an oral antiviral treatment for COVID-19 with the same molecular target (the main protease) as ritonavir-boosted nirmatrelvir—the current oral first-line treatment. We aimed to compare the clinical antiviral effects of the two drugs. Methods In an open-label, phase 2, randomised, controlled, adaptive pharmacometric platform trial, low-risk adult outpatients aged 18–60 years with early symptomatic COVID-19 (<4 days of symptoms) were recruited from hospital acute respiratory infection clinics in Thailand and Laos. Patients were randomly assigned in blocks (block sizes depended on the number of interventions available) to one of eight treatment groups, including oral ensitrelvir and oral ritonavir-boosted nirmatrelvir at standard doses, both given for 5 days, and no study drug. The primary endpoint was the oropharyngeal SARS-CoV-2 viral clearance rate assessed between day 0 and day 5 in the modified intention-to-treat population (defined as patients with at least 2 days of follow-up). Patients had four oropharyngeal swabs taken on day 0 and two swabs taken daily from days 1 to 7, then on days 10 and 14. Viral clearance rates were derived under a Bayesian hierarchical linear model fitted to log10 viral densities in standardised paired oropharyngeal swab eluates taken daily over the 5 days (14 samples). An individual patient data meta-analysis of all small molecule drugs evaluated in this platform trial using published results was also performed, adjusting for temporal trends in viral clearance. This trial is registered at ClinicalTrials.gov, NCT05041907. Findings Between March 17, 2023, and April 21, 2024, 604 of 903 patients enrolled were concurrently assigned to the three treatment groups (ensitrelvir n=202; ritonavir-boosted nirmatrelvir n=207; no study drug n=195). Median estimated SARS-CoV-2 clearance half-lives were 5·9 h (IQR 4·0–8·6) with ensitrelvir, 5·2 h (3·8–6·6) with nirmatrelvir, and 11·6 h (8·1–14·5) with no study drug. Viral clearance following ensitrelvir was 82% faster (95% credible interval 61–104) than no study drug and 16% slower (5–25) than ritonavir-boosted nirmatrelvir. In the meta-analysis of all unblinded small molecule drugs evaluated in the platform trial, nirmatrelvir and ensitrelvir had the largest antiviral effects (1157 patients). Viral rebound occurred in 15 (7%) of 207 patients in the nirmatrelvir group and 10 (5%) of 202 in the ensitrelvir group (p=0·45). Interpretation Both ensitrelvir and nirmatrelvir accelerate oropharyngeal SARS-CoV-2 viral clearance. Ensitrelvir is an effective alternative to currently available antivirals in treating COVID-19. Although COVID-19 is now generally a mild disease, it still causes substantial morbidity, particularly in vulnerable groups, and new variants or other coronaviruses could still emerge with pandemic potential. Safe effective and affordable antivirals are needed, and these are best assessed initially in pharmacometric platform trials assessing viral clearance.   Published in The Lancet Infectious Diseases (October 10, 2025)

In March 2024, a highly pathogenic avian influenza H5N1 (HPAI) clade 2.3.4.4b virus was identified in US dairy cows, with spillover to cats, poultry, and humans. Up to 30% of commercial pasteurized milk tested contained viral genome copies. The impact of residual viral remnants on host immunity is unknown. Orally ingested proteins can stimulate gut-associated lymphoid tissues, potentially inducing tolerance and altering responses to later infection. We found that milk pasteurization fully inactivated pandemic H1N1 and bovine H5N1 influenza viruses yet preserved hemagglutinin (HA) protein integrity. In mice, repeated oral exposure to inactivated virus did not alter mortality after H5N1 virus challenge. Preliminary data showed that naïve mice exposed to improperly pasteurized milk containing live H5N1 virus developed lethal infection, whereas prior H1N1 infection conferred protection. Mice with preexisting H1N1 immunity remained protected when challenged with bovine H5N1 virus after exposure to H5N1 pasteurized in milk. These findings suggest that pasteurized milk containing inactivated H5N1 virus poses minimal health risks.   Published in Science Advances: https://doi.org/10.1126/sciadv.aeb3906 

In a groundbreaking development that promises to reshape the landscape of influenza vaccination, researchers have unveiled a novel vaccine that occupies a central position within the antigenic space of the A(H5) influenza virus. This innovative vaccine formulation is engineered to confer broad immunity across diverse strains of the highly pathogenic avian influenza H5 subtype, potentially offering a crucial tool in the ongoing battle against the threat posed by influenza zoonosis and pandemics. The meticulous phylogenetic analyses that underpin this advancement were enabled by leveraging comprehensive HA nucleotide sequences sourced from extensive global databases, ensuring the vaccine’s design harmonizes with the genetic diversity of circulating H5 viruses. Central to this achievement is the integration of an unparalleled dataset comprising nearly 15,000 hemagglutinin sequences from numerous H5 isolates worldwide. By employing sophisticated bioinformatics pipelines—including sequence deduplication, alignment via advanced algorithms like MAFFT, and maximum-likelihood phylogenetic tree construction via IQ-Tree2—the team systematically delineated the antigenic relationships within the H5 subtype. This approach, combined with cutting-edge computational tools for clade prediction, allowed researchers to pinpoint a vaccine candidate uniquely positioned to bridge antigenic variations across clades, enhancing cross-protective potential.   The cultivation and maintenance of requisite cellular models such as 293T and MDCK cells supported the intricate manipulations necessary for recombinant virus production. Optimized culture conditions maintained under precisely controlled environments ensured high-fidelity replication of viral vectors employed in the reverse genetics system. The rigorous plasmid construction process involved cloning HA and NA gene segments sourced from in-house viral isolates or synthesized genes with strategically altered cleavage sites, highlighting the ingenuity in viral engineering designed to attenuate pathogenicity while preserving immunogenic features. An essential ethical and collaborative aspect of the research was the adherence to equitable benefit-sharing agreements facilitated through GISAID. By committing to openly share synthetic constructs, recombinant viruses, and ferret sera with all contributing laboratories globally, the researchers fostered an ecosystem of transparency and reciprocity critical during a time when global health challenges necessitate unified scientific responses. This commitment underscores the role of international cooperation in accelerating the translation of genomic data into actionable vaccine solutions. Strict biosafety protocols underscored every aspect of the research. Work involving recombinant viruses harboring attenuating mutations was conducted under BSL2 conditions, whereas wild-type highly pathogenic avian influenza isolates received handling within BSL3 and ABSL3+ facilities. Such meticulous adherence to biosafety practices ensured the containment of infectious agents while enabling experimental progression, particularly in ferret challenge studies that evaluated vaccine efficacy under realistic infection scenarios.   The generation of recombinant influenza viruses through reverse genetics was pivotal to vaccine development, necessitating precise transfections and virus propagation in both cell culture and embryonated egg systems. Virus titration methods employing MDCK cells and hemagglutination assays provided robust measures of viral infectivity and antigen content, facilitating rigorous standardization of vaccine stocks. Sequencing confirmation of viral segments ensured genetic fidelity of constructs, crucial for reproducibility and safety. Vaccine production hinged on advanced purification techniques that enriched viral antigens whilst eliminating extraneous components. Through ultracentrifugation with sucrose gradients and subsequent solubilization, researchers isolated and processed whole-inactivated and split-inactivated vaccines that retained native antigenic configurations critical for eliciting effective immune responses. The quantification of hemagglutinin content employed mass spectrometry with stable isotope-labeled peptides, a gold-standard approach ensuring precise antigen dosing vital for immunogenic consistency. The experimental design extended to animal models, specifically ferrets, which serve as the gold standard for assessing influenza vaccine performance due to their physiologic and immunologic similarity to humans in respiratory viral infections. Through carefully controlled prime-boost vaccination regimens and subsequent challenges with wild-type recombinant viruses, the study generated comprehensive data on immune protection, viral shedding, and pathogenesis. The deployment of implanted temperature loggers and standardized clinical scoring permitted detailed monitoring of disease progression and vaccine efficacy, with downstream histopathological and immunohistochemical analyses elucidating the interplay between viral replication and host immune response. Serological assays, including hemagglutination inhibition and virus neutralization tests, constituted the cornerstone for gauging antibody-mediated immunity. These assays, performed with stringent controls and blinded assessments, quantified functional antibody titers against a panel of recombinant and wild-type viruses, thereby mapping the breadth of vaccine-induced protection. The precision of these assays underpins the robust correlates of immunity necessary for licensure pathways and public health application.   Beyond conventional methods, the research leveraged antigenic cartography—a powerful computational technique that translates serological data into multidimensional spatial maps—to visualize and interpret the antigenic relationships among H5 viruses and vaccine-induced sera. This approach illuminates how vaccination shifts the humoral immune landscape, providing insights into antigenic drift, vaccine coverage, and potential gaps in immunity. Such granularity is instrumental in preemptively guiding vaccine strain updates in response to viral evolution. In a nuanced exploration of viral receptor specificity, the research incorporated assays using resialylated turkey red blood cells engineered to express distinct sialic acid linkages. This enabled precise characterization of viral hemagglutinin binding preferences, information pivotal for understanding host range and transmission potential. Validation using control viruses ensured assay fidelity, thereby solidifying conclusions on the biological behavior of vaccine strains. The data visualization and statistical analyses underpinning the study were executed with state-of-the-art bioinformatics tools and rigorous statistical frameworks. Employing packages within the R environment for visualization and hypothesis testing, the study provided transparent and reproducible analytic workflows. Statistical stringency through non-parametric tests and correction for multiple comparisons further assured the reliability of findings, reinforcing confidence in the vaccine’s broad immunogenicity claim. Collectively, this research represents a tour de force in influenza vaccinology, combining genomics, virology, immunology, and computational biology to deliver a vaccine candidate strategically situated at the heart of H5 antigenic diversity. Its broad immune coverage portends a significant advance in pandemic preparedness, particularly given the propensity of H5 viruses to undergo antigenic shifts that challenge existing vaccine paradigms. The methodologies and collaborative ethos exemplified herein herald a new era wherein vaccine design is as much a product of bioinformatics and global data sharing as it is of traditional virological expertise.   Research published in Nature (Oct. 15, 2025): https://doi.org/10.1038/s41586-025-09626-3   

Friday’s layoffs swept up scientists involved in responding to disease outbreaks and running an influential journal. Officials said the mistaken dismissals were being rescinded.  The Trump administration on Saturday raced to rescind layoffs of hundreds of scientists at the Centers for Disease Control and Prevention who were mistakenly fired on Friday night in what appeared to be a substantial procedural lapse. Among those wrongly dismissed were the top two leaders of the federal measles response team, those working to contain Ebola in the Democratic Republic of Congo, members of the Epidemic Intelligence Service, and the team that assembles the C.D.C.’s vaunted scientific journal, The Morbidity and Mortality Weekly Report.   After The New York Times reported the dismissals, two federal health officials said on Saturday that many of those workers were being brought back. The officials spoke anonymously in order to disclose internal discussions. The mistakes rocked an agency already in tumult, and which has been a particular target of Health Secretary Robert F. Kennedy Jr. The C.D.C. lost about a third of its staff in April; many were rehired weeks later. In August, a gunman emptied more than 500 rounds of ammunition at the agency’s headquarters in Atlanta. Later that month, Mr. Kennedy orchestrated the ouster of the agency’s director, Susan Monarez, and precipitated a series of high-profile resignations. Among the workers whose firings were revoked were members of the elite corps of “disease detectives” who are typically deployed to the sites of outbreaks. The team that puts together the M.M.W.R., which communicates the agency’s recommendations and research, has also been brought back. The employees “were sent incorrect notifications, which was fixed last night and this morning with a technical correction,” a senior administration official said. “Any correction has already been remedied.” In order to ensure that teams confronting disease outbreaks include scientists with varied expertise, they comprise staff from various parts of the agency. The two top leaders of the measles response, for example, are officially employees of the office of the director at the Global Health Center, and the office of the director at the National Center for Immunization and Respiratory Diseases. When outbreaks die down, team scientists return to their regular positions. The leaders of the measles team were let go when the administration eliminated those two offices. But just as entire units must be cut in such a layoff, entire units must also be restored.   Athalia Christie, who was “incident commander” of the measles response, had nearly 30 years of experience managing outbreaks, including Ebola, Marburg and mpox, previously called monkeypox. The White House often reached out to her for help with outbreaks. “Athalia is very well liked by the administration,” said Dr. Demetre Daskalakis, who led the respiratory disease center before he resigned in August. He had brought in Dr. Christie to lead the measles response. Another senior infectious disease expert, Maureen Bartee, was working at the Department of State. But both their jobs fell under the director’s office of the C.D.C.’s Global Health Center, which was eliminated in the layoffs. By Saturday night, employees of both offices, including Dr. Bartee and Dr. Christie, had received notices of their rehiring. They and others received a two-paragraph email saying that the notice they had received “on or about” Oct. 10 had been revoked. “You will not be affected by the upcoming RIF,” the email said. The confusion over how the disease teams are organized “demonstrates their lack of understanding that this thing is an interconnected organism,” Dr. Daskalakis said, referring to the C.D.C. “I’m happy people are back, but this damage is not easy to repair both for current staff and for people who will lead public health in the future,” he added. The agency’s entire Washington office, which was laid off on Friday, will not be rehired. Nor will employees of the office of the director of the center for injury prevention, or those at the division of violence prevention policy. “This is going to be devastating to Americans and to the global community,” said Dr. Debra Houry, who served as the agency’s chief medical officer before she resigned in August in protest against the administration’s policies. “They are dismantling public health,” she added.

Regulatory T cells, which help to dampen inflammation, are being used in clinical trials against ailments such as rheumatoid arthritis.  The class of immune cells at the centre of Monday’s Nobel prize is showing promise as a treatment for autoimmune diseases, cancer and even organ transplants — but there are still key challenges to overcome before these cells can be used in therapies in the clinic. Regulatory T cells, or Treg cells, help to prevent the body from attacking its own tissues. Earlier this week, the Nobel Prize in Physiology or Medicine went to three scientists who discovered Treg cells and helped to show how these cells regulate the immune system: immunologist Shimon Sakaguchi at the University of Osaka in Suita, Japan, Mary Brunkow, a molecular biologist at the Institute for Systems Biology in Seattle, Washington, and scientific adviser Fred Ramsdell, at the firm Sonoma Biotherapeutics in San Francisco, California. Thirty years after Sakaguchi and his colleagues reported the discovery of Treg cells, there are more than 200 clinical trials of the cells under way, for conditions such as type 1 diabetes, motor neuron disease and a host of autoimmune diseases — including multiple sclerosis, lupus and a group of rare skin disorders called pemphigus. The cells are also being tested for their ability to keep the immune system from rejecting transplanted tissues. “There’s a lot of excitement about recruiting regulatory T cell activity to treat a range of autoimmune or inflammatory disorders, but also in the context of tissue and cell transplants,” says Daniel Gray, a Treg-cell researcher at the Walter and Eliza Hall Institute of Medical Research in Parkville, Australia. But the rarity and fragility of these cells pose difficulties to their widespread application, researchers say. Finding the balance Autoimmune diseases are characterized by an imbalance of T cells: people with these conditions have more T cells that promote inflammation and kill disease-causing cells than T cells that reduce inflammation, says Joshua Ooi, who studies Treg-cell therapies for lupus at Monash University in Melbourne, Australia. “We can correct the balance by increasing the numbers of regulatory T cells,” he adds, which can help the body to suppress the pro-inflammatory T cells. Two methods to increase the number of Treg cells a person has are gaining ground, Ooi says. The first involves isolating a person’s Treg cells, growing more of them in the laboratory and infusing them back into the individual. The other method involves injecting people with drugs that trigger the body to make more Treg cells. Because Treg cells can control an overactive immune system, scientists are investigating them as a therapy to counter the side effects of bone marrow transplants, which involves building a new immune system in people with blood cancers, says Andrea Henden, a clinician–researcher at the QIMR Berghofer Medical Research Institute in Herston, Australia. Sonoma Biotherapeutics, of which Ramsdell was a co-founder, is operating clinical trials of modified Treg cells for rheumatoid arthritis and hidradenitis suppurativa — a chronic condition that causes painful bumps under the skin.   Obstacles ahead There are significant challenges to the widespread deployment of Treg cells as a therapy. One of the key issues is that these cells are rare, making up only a small proportion of the T cells in the body, says Ooi. “Often when we isolate these anti-inflammatory regulatory T cells, they can be contaminated,” he says. “Or they may also contain some pro-inflammatory cells. The cells’ rarity makes it a challenge for researchers to collect them from a person and grow more of them in the lab at a high enough quantity to treat disease effectively, Henden says. “And then they do tend, when you culture them in a lab, to want to revert to a more regular cell type,” she adds, meaning that they are no longer useful for treatment. Gray says even if infusions contain lots of Treg cells, most of the cells die quickly because of bodily processes that work to maintain a certain number of these cells. “If we can overcome those processes, we’ll be able to sustain regulatory T cells” that have been infused into an individual to try and treat autoimmune diseases, he adds. It is also tricky to coax T cells to travel to the parts of the body in which they are needed. Researchers are currently working to modify Treg cells, giving them receptors that cause the cells to home in on the location of a tissue graft or an area in which there is active disease. If these challenges can be addressed, Gray says he is confident that Treg-cell therapies will become much closer to being used in the clinic. Ooi predicts that some treatments will enter the clinic in the next few years. “These regulatory cells, in theory, could be used to treat almost anyone with an autoimmune disease,” Ooi adds.

Background Clesrovimab is a long-acting investigational monoclonal antibody against site IV of the respiratory syncytial virus (RSV) fusion protein. Data regarding the safety and efficacy of clesrovimab in healthy infants are needed. Methods We randomly assigned healthy preterm and full-term infants entering their first RSV season in a 2:1 ratio to receive one intramuscular 105-mg dose of clesrovimab or placebo. The primary efficacy end point was RSV-associated medically attended lower respiratory infection (including at least one indicator of lower respiratory infection or disease severity) through 150 days after injection. A key secondary efficacy end point was RSV-associated hospitalization during the same period. Results A total of 3614 infants received an injection: 2412 infants received clesrovimab, and 1202 infants received placebo. Through day 150 after injection, RSV-associated medically attended lower respiratory infection occurred in 60 of 2398 infants in the clesrovimab group (incidence rate over 5-month period, 2.6%) and in 74 of 1201 infants in the placebo group (incidence rate over 5-month period, 6.5%), for an efficacy of 60.4% (95% confidence interval [CI], 44.1 to 71.9; P<0.001). RSV-associated hospitalization within 150 days was reported in 9 of 2398 infants in the clesrovimab group and in 28 of 1201 infants in the placebo group, for an efficacy of 84.2% (95% CI, 66.6 to 92.6; P<0.001). Serious adverse events were reported in 278 of 2409 infants (11.5%) in the clesrovimab group and 149 of 1202 infants (12.4%) in the placebo group. Conclusions In healthy preterm and full-term infants, a single dose of clesrovimab reduced the incidence of RSV-associated medically attended lower respiratory infection and RSV-associated hospitalization, with a safety profile similar to that of placebo.   Published (Sept. 17, 2025): https://www.nejm.org/doi/full/10.1056/NEJMoa2502984 

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, utilizes membrane-bound, angiotensin-converting enzyme II (ACE2) for internalization and infection. We describe the development of a biologic that takes advantage of the proximity of the N-terminus of bound ACE2 to the three-fold symmetry axis of the spike protein to create an ultrapotent, trivalent ACE2 entry antagonist. Distinct disulfide bonds were added to enhance serum stability and a single point mutation was introduced to eliminate enzymatic activity. Through surface plasmon resonance, pseudovirus neutralization assays, and single-particle cryo-electron microscopy, we show this antagonist binds to and inhibits SARS-CoV-2 variants.   We further show the antagonist binds to and inhibits a 2003 SARS-CoV-1 strain. Collectively, structural insight has allowed us to design a universal trivalent antagonist against all variants of SARS-CoV-2 tested, suggesting it will be active against the emergence of future mutants. Structure-guided engineering of a trimeric ACE2 viral decoy reveals high affinity for spike protein, viral inhibition, and serum stability, offering a universal therapeutic strategy against SARS-CoV-2 variants and SARS-CoV-1 through symmetry-matched avidity.   Published in Communications Biology (Oct. 6, 2025): https://doi.org/10.1038/s42003-025-08819-w 

After reacquiring the rights to its non-vaccine flu preventative last year, Cidara Therapeutics has secured federal support to develop and produce the candidate, dubbed CD388, in the U.S. | The initial part of the up-to-$339 million funding will largely be used to establish U.S. manufacturing for the non-vaccine flu preventive candidate, with additional options tied to further clinical studies, Cidara said.  The remaining $281 million in options could be used to support additional studies of CD388 in specific populations, which Cidara said it would position as “a complement to the company’s plans” for an approval application to the FDA. “Clinical and non-clinical data generated to date suggest that CD388 has the potential to be an effective non-vaccine preventative for both pandemic and seasonal influenza,” Jeffrey Stein, Ph.D., Cidara’s chief executive, said in a statement. The BARDA tie-up will “both expand our commercial supply capacity, as well as ensure U.S. supply of CD388 in the event of an influenza pandemic,” he added.   CD388 is being developed as a non-vaccine alternative for flu prevention. The prophylactic is a member of the drug-Fc conjugate class, comprised of multiple copies of a potent small molecule neuraminidase inhibitor conjugated to a bespoke Fc fragment of a human antibody, according to Cidara. The company stressed in its release that drug-Fc conjugates are not vaccines or monoclonal antibodies. Rather, they are low molecular weight biologics meant to function as “long-acting small molecule inhibitors,” Cidara said.Cidara is developing CD388 to guard against all known strains of seasonal and pandemic influenza, and, because the candidate is not a vaccine, it’s expected to work in patients regardless of their immune status. Cidara regained control of CD388 from Janssen last April following the Johnson & Johnson unit’s wind-down of all infectious disease and vaccine R&D. At the time of the strategy shift, Janssen had indicated that it planned to transfer rights to the drug to another entity, according to Cidara. To recover its asset, Cidara handed Janssen $85 million upfront in a deal that also includes the potential for development, regulatory and commercial milestone payments.   The loss of a Big Pharma partner left Cidara with a funding gap, although the BARDA deal, a private stock placement led by RA Capital Management last year and other recent funding moves are likely helping bridge the gap for the San Diego company. Cidara has announced a slew of CD388 updates over the past few months, starting with a phase 2b data readout on the asset in June. In the study, dubbed Navigate, the highest 450-mg dose of CD388 conferred 76% protection against seasonal influenza in unvaccinated adults versus placebo, while lower doses of 300 mg and 150 mg conferred 61% and 58% protection, respectively.In late September, the company noted that it was moving forward with an “expanded and accelerated development plan” for the asset in which it will seek FDA approval using a single phase 3 study. The company said it aims to enroll 6,000 total subjects in the trial, which it had originally aimed to initiate next spring. Patients in the study will receive either the 450-mg dose of CD388 or placebo, Cidara said last month. The company wasted no time getting started, announcing that it had dosed the first participants in the phase 3 program just one day after affirming its late-stage development strategy. 

Creating international viral biosafety guidelines are key to clearing up confusion, regaining trust and ensuring that essential research continues. In an opinion piece published in The New York Times in March, two leading virologists argued that experiments on a coronavirus found in bats and similar to those that cause Middle East respiratory syndrome (MERS) had been conducted without sufficient safety measures. The experiments involved infecting human cells with the live bat virus to see how the virus behaved. Regulatory authorities in many countries where research on potentially dangerous viruses is conducted, including the United States, the United Kingdom, France and Germany, would require such studies to be conducted in biosafety level (BSL) 3 or 4 facilities. (There are four biosafety levels, with BSL-4 being the most stringent.) But for these experiments — which were approved by the equivalent authorities in China — the 25 researchers across 7 institutes and universities in China (including the Guangzhou National Laboratory and the Wuhan Institute of Virology) used BSL-2 procedures. They also used a negative pressure ventilation system designed to prevent microorganisms from spreading outside the laboratory.   In our view, this work and the discussion it has provoked highlights a broader and growing problem that the entire virology community needs to address. On the one hand, the threat posed by emerging infectious diseases is growing (see ‘A growing threat’), making investigations of potentially dangerous viruses more important. On the other hand, since the COVID-19 pandemic, trust in virology and science more broadly has declined and work on viruses has become more politicized. To improve trust in science — and to ensure that essential work on viruses can continue — international, standardized and transparent biosafety guidance is urgently needed. Here, we lay out how such guidance might be developed...

With some analyses generating signs of efficacy, the biotech made the case that the data support further development of the direct-acting antiviral. A phase 2b trial of Enanta Pharmaceuticals’ respiratory syncytial virus (RSV) drug candidate has missed its primary endpoint. But, with other analyses generating signs of efficacy, the biotech made the case that the data support further development of the oral, direct-acting antiviral zelicapavir. Investigators randomized 186 patients to receive zelicapavir or placebo once daily for five days. Enanta later narrowed its efficacy population to include just the 175 patients who tested positive for RSV at a central laboratory. After the treatment period, the biotech tracked participants for a further 28 days to assess the effect of zelicapavir. The time to resolution of RSV lower respiratory tract disease (LRTD) symptoms was statistically no better on zelicapavir than on placebo, causing the trial to miss its primary endpoint. Enanta reported a 0.5-day improvement over placebo in time to the complete resolution of the four LRTD symptoms in the efficacy population. Other analyses linked zelicapavir to bigger improvements in time to symptom resolution. In the efficacy population, all 13 RSV symptoms cleared up 2.2 days faster in the treatment cohort. When looking at all 29 parameters in a patient-reported respiratory infection tool, Enanta found symptoms resolved 3.6 days faster on zelicapavir.  The biotech also shared analyses of how zelicapavir compared to placebo in patients who had congestive heart failure, chronic obstructive pulmonary disease or who were aged 75 years or older. In total, 81% of participants met one of the criteria for inclusion in the subgroup analyses.   Limiting assessments to those patients, Enanta linked zelicapavir to a three-day improvement in the time to resolution of LRTD symptoms. Time to resolution of the 13 RSV symptoms was 6.7 days shorter on the study drug in the subpopulation. The difference when looking at all 29 parameters was 7.2 days.  Enanta shared data on a secondary endpoint that used another scale and on the rates of hospitalization—1.7% for zelicapavir versus 5% for placebo—to further support its argument that the results are positive. That conclusion informed comments by Scott Rottinghaus, M.D., chief medical officer of Enanta, about the next steps. “We believe the totality of these data provides strong rationale for further clinical advancement of zelicapavir,” Rottinghaus said in a statement. “Importantly, we identified multiple potential registrational endpoints for a phase 3 trial.” In a note to clients, Evercore analyst Jonathan Miller lauded the drug's “robust benefit” and stated that “no one in [the] RSV space has ever shown benefit like this with an antiviral before.” Shares in Enanta surged by about 40% to $11.03 by early afternoon on Monday from a closing price of $7.90 on Friday.    Enanta's Press Release (Sept. 29, 2025): https://ir.enanta.com/news-releases/news-release-details/enanta-pharmaceuticals-reports-positive-topline-results-its   

In a groundbreaking advancement in virology, scientists have unveiled the elusive mechanism by which Epstein–Barr virus (EBV), a pervasive human herpesvirus, infects epithelial cells. This discovery centers on the identification of desmocollin 2 (DSC2) as the principal receptor facilitating EBV entry into epithelial cells—a critical insight that reshapes our understanding of EBV transmission and paves the way for novel therapeutic interventions. EBV, long recognized for infecting B lymphocytes and epithelial cells, has posed an enigma due to the inefficiency of cell-free infection in epithelial tissues despite their susceptibility in vivo. The research unravels this paradox, highlighting the importance of direct cell-to-cell contact and the pivotal role of DSC2 in enabling efficient viral spread. EBV is notorious for its dual tropism, infecting both B cells and the epithelial linings of the oropharynx. While infection of B cells has been extensively studied, epithelial infection mechanisms have remained less clear. Historically, EBV infection of epithelial cells using free viral particles was shown to be inefficient in laboratory settings, yet clinical manifestations suggest otherwise. Prior to this study, some candidates like EphA2 had been proposed as receptors facilitating epithelial infection, but their roles were inconsistent and failed to fully explain infection dynamics. The present study, utilizing an innovative genome-wide CRISPR-Cas9 screen, identified DSC2 as a receptor indispensable for the viral entry process in epithelial cells.   The researchers conducted a comprehensive CRISPR screen aimed at pinpointing host factors that facilitate EBV entry into epithelial cells. This unbiased approach allowed them to systematically disable genes and observe the consequences on EBV infection efficiency. Through meticulous analysis, DSC2 emerged as a top candidate, with its knockout resulting in a significant decrease in viral infection rates. Intriguingly, desmocollin 3 (DSC3), a protein closely related to DSC2, was also implicated as a co-factor, not merely a redundant homolog. Together, DSC2 and DSC3 form a critical entry complex, necessary for both cell-free and — importantly — cell-to-cell contact infection modes. Building on these genetic insights, the team then employed loss- and gain-of-function experiments to validate DSC2’s role. Keratinocytes deficient in DSC2 and DSC3 showed a pronounced reduction in infection rates, both when exposed to cell-free viral particles and when co-cultured with EBV-infected B cells. Moreover, overexpressing DSC2 and DSC3 in receptor-negative cells significantly enhanced their susceptibility to infection, providing compelling evidence of their sufficiency and necessity. This dual requirement hints at a sophisticated viral entry mechanism optimized for the unique architecture of epithelial tissues, which are characterized by intricate cell-to-cell contacts. The therapeutic potential of targeting DSC2 was elegantly demonstrated by the application of monoclonal antibodies aimed at this protein. When epithelial cells were treated with antibodies directed at DSC2, EBV infection was markedly inhibited across a range of models, including normal oral keratinocytes, primary oral keratinocytes, and advanced head and neck epithelial organoids. The blockade effect became even more pronounced with a combination of antibodies against both DSC2 and DSC3, which efficiently suppressed the intimate cell-to-cell viral transfer that likely dominates natural infections. This points toward DSC2 as a highly promising target for preventative strategies, including vaccine development and antibody-based therapeutics.   Mechanistically, DSC2’s interaction with the viral glycoprotein complex gH/gL was interrogated to unravel the intricacies of EBV fusion and entry. The study found that DSC2 directly binds to gH/gL, facilitating the membrane fusion process that enables viral capsid delivery into the host cytoplasm. This interaction is critical, as it orchestrates the structural rearrangements needed for EBV to breach the epithelial cell membrane. Interestingly, attempts to rescue infection in cells lacking DSC2 and DSC3 by overexpressing EphA2, a previously proposed EBV receptor, failed—highlighting a dependency hierarchy and confirming DSC2/3 as the dominant receptor complex for epithelial infection. The implication of these findings extends beyond basic virology, impacting our understanding of EBV-associated malignancies. EBV’s ability to exploit the DSC2 receptor complex for infection suggests that disruptions or variations in desmosomal components could influence susceptibility to infection and subsequent oncogenic transformation. Since EBV is causally linked to several epithelial malignancies, including nasopharyngeal carcinoma and certain head and neck cancers, targeting the DSC2 interaction axis holds potential not just for infection prophylaxis but also for interrupting oncogenic progression. Furthermore, the discovery refines the model of EBV pathogenesis within the oral cavity and oropharynx. The efficient transmission via direct B cell and epithelial cell contact underscores the significance of tissue architecture and cellular microenvironments in viral persistence and dissemination. EBV’s preference for this contact-mediated route rather than relying solely on cell-free virions explains longstanding clinical observations and reconciles previous inconsistencies in in vitro infection studies. This study thus bridges significant gaps in viral epidemiology and transmission dynamics. The application of advanced organoid culture systems in this research represents a leap forward in modeling EBV infection in near-physiological conditions. Head and neck epithelial organoids, which recapitulate the complex differentiation and stratification of epithelial tissues, allowed for more accurate assessment of viral entry and spread. The successful inhibition of infection in these organoids using DSC2-targeting antibodies strengthens the translational prospects of these findings, indicating that therapeutic strategies developed in vitro may be applicable in vivo.   This study also raises fascinating questions about the broader role of desmosomal cadherins in viral infections. Desmocollins like DSC2 and DSC3 are key components of desmosomes, structures critical for cellular adhesion and tissue integrity. Viruses co-opting these proteins for entry point to a possible convergence of cell adhesion pathways and viral invasion mechanisms. This cross-talk may be exploited by other pathogens and represents a fertile ground for future research exploring host-microbe interactions at cellular junctions. Moreover, the elucidation of DSC2 as a primary receptor challenges prior paradigms that focused on other molecules such as integrins and Eph receptors. By highlighting a direct interaction with the viral glycoprotein complex, this study reorients therapeutic design toward desmosomal proteins, which may have been previously underappreciated. This shift in focus may inspire the generation of novel antiviral drugs that interfere specifically with the fusion process facilitated by DSC2-gH/gL binding. Given the ubiquitous prevalence of EBV and its association with a spectrum of diseases ranging from infectious mononucleosis to malignancies, the identification of DSC2 as the principal epithelial entry receptor offers a universal target. This could translate into the development of broadly applicable vaccines or monoclonal antibody therapies that prevent initial infection or limit viral spread, significantly impacting global health. In the future, clinical trials targeting DSC2 may redefine EBV management, shifting from symptomatic treatment to direct infection blockade. In summary, this pioneering work sheds light on the molecular underpinnings of EBV epithelial infection, introducing desmocollin 2 as the linchpin receptor that facilitates viral entry via direct cell-to-cell contact. The reliance on DSC2 and DSC3 for infection, the demonstrable blockade via antibodies, and the failure to rescue infection through alternative receptors compel a reevaluation of EBV biology. These discoveries have far-reaching implications for virology, oncology, and therapeutic development, marking a paradigm shift in the battle against this ubiquitous virus. The comprehensive investigation by Wang et al. not only clarifies the elusive mechanism of EBV epithelial infection but also inspires an array of future research directions. Understanding the structural basis of the DSC2-gH/gL interaction, exploring how desmosomal integrity influences EBV pathogenesis, and translating these findings into clinical applications are poised to transform the landscape of EBV prevention and treatment. This study epitomizes the power of integrative genomic screening and cellular modeling in unraveling complex viral-host interactions. As scientists continue to unravel the complexities of EBV’s interactions with its human host, the identification of desmocollin 2 as a principal entry receptor is a milestone achievement. It underscores the intricate interplay between viral evolution and host cell biology, revealing how viruses have adapted to exploit cellular machinery to ensure survival and propagation. This breakthrough serves as a blueprint for tackling other viral pathogens with similarly enigmatic infection mechanisms, showcasing how cutting-edge technologies can illuminate biological mysteries with profound clinical impact.   Research published in Nat. Microbiology (2025): https://doi.org/10.1038/s41564-025-02126-0   

Background Oncogenic viruses cause high-risk cancers in humans and are responsible for nearly 20% of all cancer cases worldwide. Currently, very limited data exists in the realm of wastewater-based viral epidemiology (WBE) of cancer-causing viruses, with existing studies using targeted approaches (i.e PCR-based approaches) which lack scalability. Our study aims to carry out WBE with hybrid-capture probes to detect and track multiple oncogenic viruses simultaneously in wastewater across Texas, USA, overcoming the drawbacks associated with targeted approaches.   Methods Here, we used a hybrid-capture approach to detect, filter and sequence oncogenic virus signals from wastewater samples collected over a duration of three years, from May 2022 to May 2025. Once viral reads were sequenced, we utilized established computational tools to characterize reads into their respective virus of origin. Next, viral abundances of each characterized oncogenic virus were tracked over time and read coverage across their genomes was measured using read mapping techniques.   Findings We detected six known oncogenic viruses, along with three suspected oncogenic viruses across all sampling locations within Texas. Over three years, viral abundance gradually increased, with distinct peaks and dips over the summer and winter months. The prevalence of high-risk viruses such as HPV and EBV rose sharply, with increases in abundance observed post-2024. We also obtained nearly 100% genome coverage with viral reads captured using a hybrid-capture technique for almost all oncogenic viruses and their types.   Interpretations Our study shows that a hybrid-capture method can efficiently overcome the challenges faced with using targeted approaches for WBE. Using this method, we get broader read coverage, coupled with concurrent and consistent real-time tracking dynamics of multiple oncogenic viruses. Our findings also emphasize the persistent circulation and rising prevalence of high-risk cancer-causing viruses, underscoring the need for sustained public health interventions to protect communities and assess viral prevalence in high-risk populations.   Preprint in medRxiv (Sept. 18, 2025): https://doi.org/10.1101/2025.09.17.25335998 

Huntington’s disease has been successfully treated for the first time using a gene therapy, which may be available in the US as soon as next year. An experimental gene therapy has become the first treatment to successfully slow the progression of Huntington’s disease. While the findings are still preliminary, the approach could be a major breakthrough and may even lead to new therapies for other neurodegenerative conditions, like Parkinson’s and Alzheimer’s. How does the therapy work? The treatment, called AMT-130, targets abnormal proteins in the brain that are responsible for the progression of Huntington’s disease. People with the condition have a genetic mutation that causes the normally-benign huntingtin protein to accumulate in toxic clumps inside brain cells, ultimately killing them. Over time, this leads to memory loss, difficulty walking, slurred speech and other symptoms. The experimental therapy, developed by the Dutch biotechnology company uniQure, stops the production of these mutant proteins. It does so by delivering genetic material to brain cells packaged inside a harmless virus. This material then directs cells to produce a small genetic molecule, called microRNA, which is designed to intercept and disable the instructions for producing the toxic protein. Think of it like a molecular stop signal. The shocking discovery that our gut microbiome drives ageing How and where is the treatment delivered? The treatment targets two brain regions first impacted by Huntington’s disease: the caudate nucleus and the putamen. Both are located deep inside the brain, so doctors use real-time brain scans to guide a thin catheter into them. The entire procedure takes 12 to 18 hours. One injection seems to be enough to permanently lower levels of mutant huntingtin in the brain...

A drug that provides near-perfect protection against H.I.V. with shots just twice a year will be made available at $40 per patient annually in low- and middle-income countries, offering new hope for ending the H.I.V. epidemic. Although current treatments can suppress H.I.V., there is no real cure, making affordable prevention crucial for turning back the virus. About 1.3 million people worldwide become infected with H.I.V. every year. The drug, lenacapavir, is given as two shots every six months. Through two deals announced on Wednesday by philanthropic organizations, the shots would cost the same as daily oral pills to prevent H.I.V., making lenacapavir a realistic choice in countries with constrained resources....

In a Q&A with STAT, Nobel winner Drew Weissman addressed concerns raised about Covid shots at a recent meeting of federal vaccine advisers. Drew Weissman Refutes RFK Jr. Adviser's Claims About Covid Shots.   On Thursday and Friday, the Centers for Disease Control and Prevention held a meeting of its Advisory Committee on Immunization Practices, a key panel that gives the CDC’s director guidance about what vaccines to recommend to the public. The panel, in the end, postponed its most controversial vote and made recommendations that seemed aimed at fostering doubts about the Covid-19 vaccines while still keeping them widely available. But some presenters and panelists raised concerns that the mRNA Covid vaccines — the ones made by Moderna and Pfizer/BioNTech — may have unconfirmed safety issues. In particular, Retsef Levi, who chairs ACIP’s working group on Covid vaccines, raised concerns that mRNA, the lipid nanoparticles they are encapsulated in, and the spike protein the vaccines produce may all persist and be widely distributed in the body. He also said they may provoke an immune response that is not understood and could even change the way the body reads its own genetic material. Moderna and Pfizer said that the claims were refuted by well-done studies that met global regulatory standards. STAT posed questions about these claims to Drew Weissman, a professor at the University of Pennsylvania and co-recipient of the 2023 Nobel Prize in physiology or medicine for his discoveries that enabled the creation of mRNA-based Covid-19 vaccines. That conversation, edited for length and clarity, follows.   At the ACIP meeting, there were a lot of discussions about reports of mRNA being widely distributed in the body or persisting.   If you look in the literature you can find papers that say that the earth is flat, you can find papers that say DNA isn’t double stranded. You can find anything. The problem is there’s thousands, tens of thousands, hundreds of thousands, millions of other papers that refute that. What these people do, is that they search, they find one paper or two papers that make an outlandish claim based on bad data that hundreds or thousands or tens of thousands of other papers refute, they don’t mention everything that refutes it. They only mention, oh, look, I found a paper that says spike is around for nine months! It’s just not true. Many good studies have not seen that. The RNA is gone in days. It doesn’t go to the brain. It doesn’t go to the eyes. What those studies did is they put huge doses of RNA into a mouse and used very sensitive assays, and that’s where it went. It goes everywhere. If you put a vaccine equivalent dose, you see it in the muscle, you see it in the draining lymph node, and that’s about it.   But how certain are we that mRNA is not continuing to produce spike protein? For instance, the preprint authored by Akiko Iwasaki, which includes well-respected Yale researchers. That’s a paper that found at least residual spike protein.   The problem is they used a bad assay to measure spike. It’s an ultra, ultra-sensitive assay, but it makes a lot of errors, and you don’t believe anything unless it’s above a certain level as real. What they reported was in the unknown area where it could just be noise in the assay versus real spike. Many other assays using good experiments, using good assays, don’t find spike protein circulating. How sure are you? How sure are you that there is no case of mRNA being distributed more widely in the body?   I know it’s not distributed widely. I mean, we showed that back in 2017 at vaccine doses. We’ve looked at mice, we’ve looked at macaques, we’ve looked at rabbits, and we’ve done as much as we could on humans at a vaccine dose. You don’t see RNA circulating in the placenta, in the testes, in the heart, in the eye, in the brain, all the places that they list. We and many others have looked and we just don’t see it.   And the mRNA could not be persistent? Could one dose of mRNA continue to make spike protein for months in a rare patient?   It is absolutely impossible. MRNA is degraded incredibly rapidly. When you modify it, it’s a little slower. It’ll last 24 hours. It never, ever lasts six months. That’s just impossible. But I can make an assay that gives you any answer you want, and that’s what these people have done.   I’d like to read specifically from the concerns about mRNA vaccines made by Dr. Retsef Levi, the chair of the working group for ACIP. We covered his concern about “wide biodistribution and prolonged persistence of spike, mRNA and nano-lipid particles.” He also wrote that there are prolonged immune responses that are not understood. In people who are vaccinated, it was incredibly rare to see that. It was mostly immunized mice. You can always find people who react differently. You can always find people who don’t respond, for instance.   Another concern is a “frame shift leading to production of unintended proteins and related immune response,” meaning the vaccine has changed the way that DNA is read to make proteins.   That was one paper that claimed that uridine caused a frameshift mutation and induced immune responses. It was never seen in thousands and thousands of other studies.   What about the issue of DNA contamination — that DNA impurities are present at too high a level and that the lipoprotein that allows the mRNA to get into cells could lead to them being taken up?   Just about every vaccine has DNA contamination. If it is made from eggs, if it is made from living cells, if it is an inactivated virus, if it’s a live virus. They’re all grown in cells and cells have DNA. So when you purify the virus, you get very low levels of DNA contamination. We’ve never seen an adverse event.  And these are minute amounts. For mRNA, the DNA strands are a couple of nucleotides long. We’ve never seen them integrate into the chromosomes or cause cancer, it just hasn’t been seen. People give a milligram dose of DNA plasmid as a vaccine, it’s in clinical trials right now. We don’t see any adverse events from that.   Is there anything else you’d like to say?   What concerned me more from these meetings is they voted against combined childhood vaccines. They voted against making Covid-19 vaccines available to larger populations. They’re going to likely vote against giving hepatitis B vaccines to infants. So if you look back at the data, 250 years ago, 40% of kids never made it to adulthood. Today, it’s 4%. The majority of that decrease is due to vaccines. Vaccines have saved more lives than any other type of medical intervention, including antibiotics, including everything. Vaccines have saved an enormous number of lives.  No vaccine was tested more extensively than the RNA vaccines, and no vaccine was given to more people than the mRNA vaccines, and they were found to be incredibly safe, safer than any other vaccine platform and effective. They saved 20 million lives, and they stopped a pandemic that was shutting down the world.

Purpose   Early detection of HPV-associated oropharyngeal cancer (HPV+OPSCC), the most common HPV cancer in the United States, could reduce disease-related morbidity and mortality, yet currently, there are no early detection tests. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive and specific biomarker for HPV+OPSCC at diagnosis. It is unknown if ctHPVDNA is detectable prior to diagnosis, and thus it’s potential as an early detection test.   Methods   Plasma samples from the MassGeneralBrigham biobank collected 1.3-10.8 years prior to diagnosis from HPV+OPSCC patients (n = 28) and age- and sex-matched controls (n = 28) were blinded and run on a newly developed and validated multi-feature HPV whole genome sequencing liquid biopsy assay and a validated HPV antibody assay.   Results   ctHPVDNA results were positive in 22/28 pre-diagnostic samples from HPV+OPSCC cases (sensitivity 79%) with a maximum lead time of 7.8 years. ctHPVDNA results were negative in all controls (0/28 controls, 100% specificity). Diagnostic accuracy was highest within four years of cancer diagnosis and was higher than HPV Ab detection within the same time frame (p-value 0.004). Application of a machine learning model trained and tested on an independent cohort of 306 cases and controls increased the sensitivity of detection to 27/28 cases (overall sensitivity 96%) and the maximum lead time to 10.3 years.   Conclusions   Circulating tumor HPV DNA can be detected in the blood years prior to diagnosis with HPV+OPSCC, with high specificity, in a case-control cohort of 56 participants. ctHPVDNA detection alone, or in combination with previously identified serological biomarkers may be a feasible approach to early detection of HPV+OPSCC.   Published Sept. (10, 2025): https://doi.org/10.1093/jnci/djaf249 

Viral infectious diseases have caused millions of deaths worldwide. Antiviral agents are critical for controlling these infections; however, an open-access database dedicated specifically to antiviral agents remains unavailable. Here, we present AntiviralDB (https://www.antiviraldb.com/), an expert-curated resource that compiles both approved and experimental antiviral agents with laboratory-confirmed in vitro activity against a broad spectrum of human viruses. These include the human immunodeficiency virus, coronaviruses, hepatitis viruses, influenza virus, respiratory syncytial virus, herpes simplex virus, varicella-zoster virus, human cytomegalovirus, human papillomavirus, dengue virus, Zika virus, Ebola virus, mpox virus, norovirus, chikungunya virus, and 16 other common or life-threatening pathogens.   Each antiviral agent in the database is annotated with key information, including its molecular target, in vitro antiviral activity (IC50, EC50, and CC50 across specific viral strains and cell lines), mechanism of action, and relevant pharmacokinetic and pharmacodynamic parameters. AntiviralDB also provides clinical efficacy and safety data derived from randomized clinical trials. Unlike existing drug databases, AntiviralDB offers two distinctive features: (i) standardized laboratory protocols for antiviral drug screening under appropriate biosafety conditions and (ii) clinical guidelines for the therapeutic use of antiviral agents against viral infections. By serving as a comprehensive repository of antiviral agents and their clinical applications, AntiviralDB aims to advance antiviral drug discovery and support the effective clinical management of viral infectious diseases. IMPORTANCE Over the past decade, viral infectious diseases have caused significant morbidity and mortality worldwide, underscoring the urgent need for effective antiviral therapies. However, there is a lack of an open-access database that consolidates detailed information on antiviral agents, clinical guidelines, and laboratory protocols. To address this need, AntiviralDB was developed to integrate extensive data on antiviral agents—including clinical efficacy, safety profiles, pharmacokinetic parameters, and in vitro and in vivo activities—together with standardized experimental protocols and clinical treatment guidelines. This resource empowers researchers and clinicians to (i) identify promising antiviral candidates for controlling infectious diseases, (ii) accelerate the discovery and development of novel therapeutics, (iii) optimize the clinical use of existing antiviral drugs, and (iv) enhance a quick response to emerging viral outbreaks.   Published in Mbio (Sept. 11, 2025): https://doi.org/10.1128/mbio.02013-25 

An immunocompromised man endured ongoing acute COVID-19 for more than 750 days. During this time, he experienced persistent respiratory symptoms and was hospitalized five times. In spite of its duration, the man's condition differs from long COVID as it wasn't a case of symptoms lingering once the virus had cleared out, but the viral phase of SARS-CoV-2 that continued for over two years. While this record may be easy to dismiss as something that occurs only to vulnerable people, persistent infections have implications for us all, US researchers warn in their new study. "Long-term infections allow the virus to explore ways to infect cells more efficiently, and [this study] adds to the evidence that more transmissible variants have emerged from such infections," Harvard University epidemiologist William Hanage told Sophia Abene at Contagion Live. "Effectively treating such cases is hence a priority for both the health of the individual and the community."   Boston University bioinformatician Joseline Velasquez-Reyes and colleagues' genetic analysis of viral samples collected from the patient between March 2021 and July 2022 revealed what the virus was up to during its extended invasion. The virus's mutation rate within the patient ended up similar to that usually seen across a community. What's more, some of these mutations were awfully familiar. Spike mutations matched positions of those seen in the omicron variant of SARS-CoV-2, for example. Within just one person, the same types of mutations that led to the emergence of the faster multiplying omicron variant were on their way to being repeated. This backs the theory that omicron-like changes developed from selection pressures the virus experiences inside our bodies, the researchers explain. The patient, who has advanced HIV-1, believes they contracted SARS-CoV-2 in mid-May of 2020. During this time, he was not receiving antiretroviral therapy, nor able to access the necessary medical care despite suffering from respiratory symptoms, headaches, body aches, and weakness. The 41-year-old had an immune helper T-cell count of just 35 cells per microliter of blood, explaining how the virus managed to persist for so long. The healthy range is 500 to 1,500 cells per microliter. Luckily, in this case at least, the stubborn invader was not highly infectious.   "The inferred absence of onward infections might indicate a loss of transmissibility during adaptation to a single host," Velasquez-Reyes and team suspect. Still, there's no guarantee other infections that establish long-term camps inside us will follow the same evolutionary path, which is why experts are wary and calling for continued close monitoring of COVID and adequate access to healthcare for everyone. "Clearing these infections should be a priority for health-care systems," the researchers conclude. To reduce the chances of problematic mutations, physicians and researchers urge communities to keep up vaccinations and continue masking in crowded, enclosed areas.   Research published in TheLancet  (Septmember 2025): https://doi.org/10.1016/j.lanmic.2025.101122 

Influenza A viruses (IAVs) have historically posed significant public health threats, causing severe pandemics. Viral host specificity is typically constrained by host barriers, limiting the range of species that can be infected. However, these barriers are not absolute, and occasionally, cross-species transmission occurs, leading to human outbreaks. Early identification of changes in IAV host specificity is, therefore, critical. Despite advancements, identifying host susceptibility from genomic sequences during outbreaks remains challenging. Timely predictions are critical for effective real-time outbreak management and risk mitigation during the early stages of an epidemic.   To address this, we proposed Flu-level Convolutional Neural Networks (Flu-CNN), a model designed to analyze genomic segments and identify IAV host specificity, with a particular focus on avian influenza viruses that could potentially infect humans. Extensive evaluations on large-scale genomic datasets containing 911,098 sequences show that Flu-CNN achieves an impressive 99% accuracy in determining host specificity from a single genomic segment, even for high-risk subtypes like H5N1, H7N9, and H9N2, which have a limited number of viral strains. Given its high level of accuracy, the model was applied to identify key mutations and assess the zoonotic potential of these strains. Furthermore, our study presents a pioneering approach for predicting IAV host specificity, offering novel insights into the evolutionary trajectory of these viruses. The model’s significance extends beyond evolutionary analysis, playing a pivotal role in outbreak surveillance and contributing to efforts aimed at preventing the viral spread on a global scale.   Published (August 22, 2025) in Human Genomcs: https://doi.org/10.1186/s40246-025-00812-y

Background Wastewater-based epidemiology can inform the understanding of infectious disease occurrence in communities. Quantitative information on shedding of pathogen biomarkers in excretions that enter wastewater is needed to link measurements of pathogen biomarkers to rates of disease occurrence. Methods We compile, summarise, and compare data on shedding of human norovirus, rotavirus, hepatitis A virus, and adenovirus group F in stool, vomit, urine, saliva, mucus, and sputum using a systematic review and meta-analysis approach. Findings We provide summaries of measured concentrations of the viruses across excretions where data exist. We provide longitudinal shedding profiles in terms of concentrations and positivity rates. Duration of shedding and day of peak shedding are also provided. Interpretation There are limited data available for excretions other than stool, and limited data available for adenovirus group F. The aggregated data provided herein can serve as model inputs to translate wastewater enteric virus biomarker concentrations to disease occurrence rates. The study highlights data gaps and research needs.   Published in eBiomedicine (August 5, 2025): https://doi.org/10.1016/j.ebiom.2025.105878 

A child in Los Angeles County has died from a rare but always fatal brain disorder that develops years after a measles infection. Experts underscore the need for vaccination to protect the most vulnerable. The first dose of the vaccine is typically not administered until one year of age. Experts say the death underscores the need for high levels of vaccination in a population to protect the most vulnerable against the disease, as well as from side effects that can occur long after the initial illness has passed. “This case is a painful reminder of how dangerous measles can be, especially for our most vulnerable community members,” said Los Angeles County Health Officer Muntu Davis in a recent statement. The child who died suffered from subacute sclerosing panencephalitis (SSPE), a progressive brain disorder that usually develops two to 10 years after a measles infection. The measles virus appears to mutate into a form that avoids detection by the immune system, allowing it to hide in the brain and eventually destroy neurons. “It’s just a virus that goes unchecked and destroys brain tissue, and we have no therapy for it,” said Walter Orenstein, an epidemiologist and professor emeritus at Emory University, to Scientific American earlier this year.   People with SSPE experience a gradual, worsening loss of neurological function and usually die within one to three years after diagnosis, according to the Los Angeles County Health Department. The disorder affects only about one in every 10,000 people who contract measles. But the risk may be as high as about one in 600 for those who are infected as infants. “There is no treatment for this. Children who suffer from this will always die,” said Paul Offit, director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia, in a previous interview with Scientific American. Offit, who had measles himself in the 1950s, has seen five or 10 cases of SSPE in his career.  SSPE is one of several side effects of measles that go beyond the coughing, runny nose and characteristic rash of the original infection. Measles can also cause encephalitis, a faster-occurring brain inflammation, in one in every 1,000 people who are infected because the virus causes the immune system to attack a protein produced by certain brain cells. This inflammation kills about one in five people who develop it. Measles also causes “immune amnesia”: the virus seems to attack the immune system’s B cells, which remember previous pathogens the body has been exposed to, resulting in reduced immunity. There is some evidence this effect can last for a couple of years, making those who get measles more susceptible to other infectious diseases. These side effects are of particular concern because the measles virus is highly contagious—an order of magnitude more than seasonal influenza. With measles, viral particles emitted by coughing or sneezing can linger in a room for hours after the infected person has left. One infected person infects 15 more people on average.   This year the U.S. saw its largest single measles outbreak since the disease was declared eliminated in 2000;the recent outbreak occurred mainly in Texas, New Mexico, Kansas and Oklahoma. Most of those infected were unvaccinated or had an unknown vaccination status. Of those infected, 12 percent were hospitalized, and three died of complications from the infection. The fatal cases included the first death of a child from measles in the U.S. in 22 years. Measles used to infect three million to four million people in the nation every year until vaccines became available in 1963. The measles vaccine is administered in two doses: typically, the first is given between 12 and 15 months of age and the second is given at four to six years. One dose is 93 percent effective at protection against infection, and two doses are 97 percent effective. Contrary to claims by Secretary of Health and Human Services Robert F. Kennedy, Jr., measles cannot be treated by vitamin A or cod liver oil. There is no cure or treatment for the disease beyond treatment of symptoms. The only effective means of combatting measles is widespread vaccination. At least 95 percent of a population must be vaccinated to prevent the spread of the disease and to protect either those who are too young to receive it or those who cannot be vaccinated because of other health conditions. “Infants too young to be vaccinated rely on all of us to help protect them through community immunity,” Davis said in his recent statement. “Vaccination is not just about protecting yourself—it's about protecting your family, your neighbors, and especially children who are too young to be vaccinated.”

A mix of three antibodies seems to protect mice against several strains of influenza and could one day be useful against seasonal flu or pandemics. A cocktail of antibodies could give us a new weapon to fight seasonal flu and new strains that cause pandemics. The mix protected mice from various strains of influenza, but hasn’t yet been tested in humans. Most flu treatments and vaccines rely on prompting the body to make proteins called neutralising antibodies. These bind to specific strains of a virus, preventing it from infecting cells. Such medical interventions can be very effective, but can take many months to develop and may lose effectiveness if the virus mutates. This is why flu vaccines are updated seasonally and why researchers are working on a universal vaccine that would protect against all flu strains or even against all viruses. Silke Paust at the Jackson Laboratory in Farmington, Connecticut, and her colleagues have a different approach. They are focusing on non-neutralising antibodies, another kind of protein produced by the immune system. Researchers have largely ignored these proteins for fighting infectious diseases because they don’t prevent infection. Instead, they empower the immune system to kill the virus responsible by tagging already infected lung cells. “We are making a therapy, not a vaccine. What we are trying to do is create a drug that you can give prophylactically or therapeutically after infection to prevent severe disease and death,” says Paust.   Paust and her colleagues focused on antibodies that would target an influenza virus protein in a region called M2e, which is essential for the virus to replicate itself and is nearly unchanged in all flu strains. The researchers conducted a series of experiments in which they tested how well the antibodies worked individually or in combination in mice that were infected with a flu virus, and found that combining three antibodies gave the best results. They tested the cocktail in mice exposed to two strains of H1N1 influenza, including the one that caused the 2009 swine flu pandemic and gave rise to the currently circulating H1N1, and two avian influenza strains: H5N1, which is infecting wildlife around the world and some livestock in the US, and H7N9, which can be deadly to both humans and other animals. The researchers discovered that the cocktail reduced disease severity and the amount of virus in the lungs, and improved survival rates in both healthy and immunocompromised animals. For H7N9, for example, all mice survived when given the antibody cocktail in the first three days after infection, 70 per cent survived if treated on day four and 60 per cent if treated on day five. It is the first time we have seen such broad protection against flu in living animals, says Paust. The cocktail also worked when given before infection, so the drug could potentially be used in advance to prevent illness.   Even after 24 days of treatment, there were no signs of the virus successfully mutating to resist it. “If the virus wants to mutate away from the therapy, it would have to evade all three antibodies because they don’t bind in exactly the same way,” says Paust. “As a proof of principle, this shows how a cocktail of antibodies might be utilised as a drug to treat people during a flu pandemic which could be used in parallel to vaccines,” says Daniel Davis at Imperial College London. “But this would need to be tested in humans before this can be considered a true medical advance.” The next step, says Paust, is to alter the antibodies that target M2e to make them look like human proteins, so the immune system doesn’t see them as invaders and attack them, which has been done before with many antibodies. If that works, safety and efficacy trials would follow. Paust envisions the cocktail being used as a stockpiled drug to fight seasonal flu outbreaks. “Ideally, this would be something to give to high-risk patients at the beginning of the season,” she says. “It would mean that they wouldn’t get very ill, essentially.”   Research Published in Science Advances: https://www.science.org/doi/10.1126/sciadv.adx3505 

Background A subgroup analysis of the COVID-OUT trial's long-term outcome found that starting metformin within 3 days of coronavirus disease 2019 (COVID-19) diagnosis reduced post–COVID-19 condition (PCC) incidence by 63% in overweight or obese individuals. However, its generalizability remains uncertain.   Objectives To evaluate the effectiveness of metformin in preventing PCC in adults with overweight or obesity who had a recent COVID-19 infection.   Design A retrospective cohort study using a sequential target trial emulation framework.   Data Sources The United Kingdom primary care data from the Clinical Practice Research Datalink Aurum database from March 2020 to July 2023.   Participants Adults with overweight or obesity (body mass index ≥ 25 kg/m²) and a record of severe acute respiratory syndrome coronavirus 2 infection were included. Exclusions included metformin use in the prior year or metformin contraindications.   Measurements The outcome was PCC, defined by a PCC diagnostic code or at least 1 World Health Organization–listed symptoms between 90 and 365 days after diagnosis, with no prior history of the symptom within 180 days before infection. The pooled hazard ratio and risk difference for the incidence of PCC were adjust for baseline characteristics.   Results Among 624 308 patients, 2976 initiated metformin within 90 days of COVID-19 diagnosis. The 1-year risk difference for PCC in the intention-to-treat analysis was −12.58% (hazard ratio 0.36; 95% CI, 0.32–0.41), with consistent results in subgroup analyses.   Limitations Findings may not apply to individuals with a normal body mass index.   Conclusions Early metformin treatment in overweight or obese individuals may reduce PCC risk. Further research is needed to confirm causality and clarify metformin's role in PCC management.   Published in Clinical Infect. Diseaseses (Sept.1): https://doi.org/10.1093/cid/ciaf429

He was only 37 when he made a discovery that challenged the existing tenets of biology and led to an understanding of retroviruses and viruses, including H.I.V.  David Baltimore, a biologist who in 1975 won a Nobel Prize for a startling discovery that seemed to rock the foundations of the fledgling field of molecular biology, died on Saturday at his home in Woods Hole, Mass. He was 87. The cause was complications of several cancers, his wife, Alice Huang, said. Dr. Baltimore was only 37 when he made his Nobel-winning discovery, upending what was called the central dogma, which stated that information in cells flowed in only one direction — from DNA to RNA to the synthesis of proteins. Dr. Baltimore showed that information can also flow in the reverse direction, from RNA to DNA. The key was finding a viral enzyme, called a transcriptase, that reversed the process. The discovery led to an understanding of retroviruses and viruses, including H.I.V., that use this enzyme. Today, gene therapies with disabled retroviruses are used to insert good genes into patients’ DNA to correct genetic diseases. Admired and envied, lionized and attacked, Dr. Baltimore spent most of his life in the scientific limelight, a towering figure of modern biology. He was president of two leading universities and an early proponent of AIDs research; he also fought what turned out to be trumped-up charges of fraud in a highly publicized decade-long case, beginning in the 1980s, involving accusations that a researcher in his lab had misreported data.   In 1968, Dr. Baltimore joined the faculty of the Massachusetts Institute of Technology. Two years later, he began the work that would win him the Nobel Prize. It was a time when a group of Young Turks ruled the M.I.T. biology department. Dr. Baltimore was most definitely one of them, with a coterie of graduate student aspirants who hung onto his every word and vied to work in his lab. “Most of us young faculty at M.I.T. were thought of as arrogant,” his friend David Botstein, a former Princeton professor, said in an interview for this obituary. “David fit into that culture of competitive smartness. He was the smartest of all.” Dr. Baltimore first presented his data overthrowing the central dogma at an evening seminar in an M.I.T. classroom, inviting just faculty and friends. Dr. Botstein was there. “I remember it like it was yesterday,” Dr. Botstein said. “It was in room 16-310. He gave this talk and I remember walking out of it and saying to Maurie Fox” — another faculty member — “‘He is going to get the Nobel Prize for that.’” A few years later, it happened.    Dr. Huang, an accomplished biologist who was working with Dr. Baltimore in his lab when he made the prizewinning discovery, was among the first to know. In 1975 she was at a conference in Copenhagen where George Klein, a scientist who was scheduled to give a talk, suddenly announced that he had been with a committee that decided on Nobel Prizes. In half an hour, Dr. Klein said, the committee would announce that Dr. Baltimore had won the Nobel Prize for Physiology or Medicine, along with two others: Howard Temin, who had independently made the same discovery, and Renato Dulbecco, for his work on tumor viruses. Dr. Huang “immediately got on the phone and called me,” Dr. Baltimore said in an interview for this obituary. He speculated that he was probably “the only person who ever was told he had won a Nobel Prize by his wife.” David Baltimore was born on March 7, 1938, in Manhattan to Richard and Gertrude (Lipschitz) Baltimore. His parents moved to Great Neck, N.Y., on Long Island, when he was in second grade so he and his younger brother, Robert, could attend better schools......