Sulfur-containing class of broad-spectrum antivirals improves influenza virus vaccine development
Year: 2026
Type: article
Abstract: Enveloped viruses are significant zoonotic disease threats with the potential to cause global pandemics. We identified a class of small-molecule sulfur-containing antiviral compounds (XM series) that broadly inhibit enveloped viruses. Multidisciplinary approaches revealed that XM compounds alter the viral membrane lipid chemical composition, enhance membrane order within the hydrophobic bilayer, and increase membrane phase transition temperatures. This mechanism inhibits membrane fusion and viral entry, while leaving the viral glycoproteins and genomes largely unaffected. Leveraging these unique properties, we develop a proof-of-concept whole inactivated influenza virus (IIV) vaccine using XM-01 (XM-01-IIV). In a mouse model, XM-01-IIV elicit significantly enhanced neutralizing antibody responses against hemagglutinin and neuraminidase compared to traditional paraformaldehyde-inactivated vaccines. Further, XM-01-IIV reduces morbidity and mortality following influenza challenge, achieving protection comparable to live virus vaccination. This promising class of broadly acting antivirals can be highly impactful in the development of highly potent inactivated vaccines for enveloped viruses.
Source: Nature Communications
Authors: David W. Buchholz, Armando Pacheco, Sreetama Pal, I. Abrrey Monreal, Shi Xu, Brian Imbiakha, Julie Sahler, Mason Jager, Alex Liqi Lai, Erik M. Contreras, Shahrzad Ezzatpour, Brandan Cook, Elshan Ralalage, Qian Liu, Yao Yu Yeo, Andrew Ma, Haewon Byun, Obaed Shah, J. Lizbeth Reyes Zamora, Niraj K. Shil, Sara Jones-Burrage, Suzanne M. Pritchard, Chuntao Yang, Yu Zhao, Zeinab J. Mohamed, Cheyan Xu, Michael J. Jung, Gerlinde R. Van de Walle, Suchetana Mukhopadhyay, Masako Shimamura, Alan G. Goodman, Michele Hardy, Santanu Bose, Anthony V. Nicola, Jack H. Freed, Avery August, Susan Daniel, Petr Chlanda, Jace W. Jones, Ming Xian, Hector C. Aguilar
Institutions: Cornell University, New York State College of Veterinary Medicine, Washington State University, Brown University, University of California, Los Angeles, Indiana University Bloomington, Indiana University, Nationwide Children's Hospital, Abigail Wexner Research Institute, Montana Technological University, Heidelberg University, University Hospital Heidelberg, University of Maryland, Baltimore
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Deutsche Forschungsgemeinschaft, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: G1436661812, G143962596, G1692958442, G2828991432, Regulation of IL10 production in CD8+ T cells during Flu infection by tyrosine kinase Itk, Low pH-mediated HSV fusion and entry, Mechanisms of Nipah virus fusion and entry, Viral and cellular mechanisms of HSV fusion and entry, Molecular and cellular mechanism regulating innate immunity and inflammation during pattern recognition receptor activation and respiratory virus infection, G4724125240, G4783087731, G5197873167, G561102459, Mechanism of membrane inactivation method to prepare enveloped virus vaccines, Training in Biotechnology: Emphasis in Protein Chemistry, G6461157608, Immuno-Engineering: Integrated Engineering and Immunology Training, Novel Sulfide Releasing Agents for Ischemic Injury, G7843559024, Cornell Initiative for Maximizing Student Development, Itk mediated tuning of CD8+ memory T cell development, Graduate Training Program in Comparative Medicine
OpenAlex ID: W7118421971