Nature Communications

Sulfur-containing class of broad-spectrum antivirals improves influenza virus vaccine development

D David W. Buchholz A Armando Pacheco S Sreetama Pal I I. Abrrey Monreal S Shi Xu B Brian Imbiakha (Department of Medicine, Washington University School of Medicine) J Julie Sahler M Mason Jager A Alex Liqi Lai E Erik M. Contreras S Shahrzad Ezzatpour B Brandan Cook E Elshan Ralalage Q Qian Liu Y Yao Yu Yeo A Andrew Ma H Haewon Byun O Obaed Shah J J. Lizbeth Reyes Zamora N Niraj K. Shil S Sara Jones-Burrage S Suzanne M. Pritchard C Chuntao Yang Y Yu Zhao Z Zeinab J. Mohamed C Cheyan Xu M Michael J. Jung G Gerlinde R. Van de Walle S Suchetana Mukhopadhyay M Masako Shimamura A Alan G. Goodman M Michele Hardy S Santanu Bose A Anthony V. Nicola J Jack H. Freed (Department of Chemistry) A Avery August S Susan Daniel P Petr Chlanda J Jace W. Jones M Ming Xian (Department of Chemistry) H Hector C. Aguilar

Abstract

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.

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Article Details

Volume / Issue Vol. 17, Issue 1
Published January 06, 2026
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio
ISSN: 2041-1723 Open Access Life Sciences

Authors (41)

D

David W. Buchholz

A

Armando Pacheco

S

Sreetama Pal

I

I. Abrrey Monreal

S

Shi Xu

B

Brian Imbiakha

Department of Medicine, Washington University School of Medicine

J

Julie Sahler

M

Mason Jager

A

Alex Liqi Lai

E

Erik M. Contreras

S

Shahrzad Ezzatpour

B

Brandan Cook

E

Elshan Ralalage

Q

Qian Liu

Y

Yao Yu Yeo

A

Andrew Ma

H

Haewon Byun

O

Obaed Shah

J

J. Lizbeth Reyes Zamora

N

Niraj K. Shil

S

Sara Jones-Burrage

S

Suzanne M. Pritchard

C

Chuntao Yang

Y

Yu Zhao

Z

Zeinab J. Mohamed

C

Cheyan Xu

M

Michael J. Jung

G

Gerlinde R. Van de Walle

S

Suchetana Mukhopadhyay

M

Masako Shimamura

A

Alan G. Goodman

M

Michele Hardy

S

Santanu Bose

A

Anthony V. Nicola

J

Jack H. Freed

Department of Chemistry

A

Avery August

S

Susan Daniel

P

Petr Chlanda

J

Jace W. Jones

M

Ming Xian

Department of Chemistry

H

Hector C. Aguilar

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