Evidence map›Paper›PMID 41495036›Full record

ArticleNature communications2026

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

David W Buchholz, Armando Pacheco, Sreetama Pal, I Abrrey Monreal, Shi Xu, Brian Imbiakha, Julie Sahler, Mason Jager, Alex Liqi Lai, Erik M Contreras and 31 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Membrane-Targeting Antivirals.International journal of molecular sciences · 2025
    Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

41 authors.

David W Buchholz *Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-8874-6648
Armando Pacheco *Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Sreetama PalRobert Frederick Smith School of Chemical and Biomolecular Engineering, College of Engineering, Cornell University, Ithaca, NY, USA.
I Abrrey MonrealDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Shi XuDepartment of Chemistry, College of Arts and Sciences, Washington State University, Pullman, WA, USA.ORCID http://orcid.org/0000-0002-4325-6503
Brian ImbiakhaDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Julie SahlerDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0003-1852-9511
Mason JagerDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-6036-9895
Alex Liqi LaiDepartment of Chemistry and Chemical Biology, College of Arts and Sciences, Cornell University, Ithaca, NY, USA.
Erik M ContrerasDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Shahrzad EzzatpourDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Brandan CookDepartment of Chemistry, College of Arts and Sciences, Washington State University, Pullman, WA, USA.
Elshan RalalageDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.
Qian LiuPaul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Yao Yu YeoDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Andrew MaDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0002-6344-5950
Haewon ByunDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Obaed ShahDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
J Lizbeth Reyes ZamoraDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0003-3000-817X
Niraj K ShilDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Sara Jones-BurrageDepartment of Biology, Indiana University, Bloomington, IN, USA.
Suzanne M PritchardDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Chuntao YangDepartment of Chemistry, College of Arts and Sciences, Washington State University, Pullman, WA, USA.
Yu ZhaoDepartment of Chemistry, College of Arts and Sciences, Washington State University, Pullman, WA, USA.
Zeinab J MohamedRobert Frederick Smith School of Chemical and Biomolecular Engineering, College of Engineering, Cornell University, Ithaca, NY, USA.
Cheyan XuRobert Frederick Smith School of Chemical and Biomolecular Engineering, College of Engineering, Cornell University, Ithaca, NY, USA.
Michael J JungDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.
Gerlinde R Van de WalleDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0002-2064-8029
Suchetana MukhopadhyayDepartment of Biology, Indiana University, Bloomington, IN, USA.ORCID http://orcid.org/0000-0001-9230-4746
Masako ShimamuraCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Alan G GoodmanSchool of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.ORCID http://orcid.org/0000-0001-6394-332X
Michele HardyCollege of Letters, Sciences and Professional Studies, Montana Technological University, Butte, MT, USA.
Santanu BoseDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Anthony V NicolaDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Jack H FreedDepartment of Chemistry and Chemical Biology, College of Arts and Sciences, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0003-4288-2585
Avery AugustDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0003-4968-3415
Susan DanielRobert Frederick Smith School of Chemical and Biomolecular Engineering, College of Engineering, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-7773-0835
Petr ChlandaDepartment of Virology, Center for Infectious Diseases, Uni-Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-7782-2139
Jace W JonesDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-0460-0380
Ming XianDepartment of Chemistry, College of Arts and Sciences, Washington State University, Pullman, WA, USA.ORCID http://orcid.org/0000-0002-7902-2987
Hector C AguilarDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. HAguilarCarreno@mednet.ucla.edu.ORCID http://orcid.org/0000-0001-6879-8360

Funding

TRAINING IN BIOTECHNOLOGY: EMPHASIS ON PROTEIN CHEMISTRYT32GM008336 · NIGMS · WASHINGTON STATE UNIVERSITY · PI CALL, DOUGLAS R. · 1989 to 2023
$8.9M
Graduate Training Program in Comparative MedicineT32OD011000 · OD · CORNELL UNIVERSITY · PI Amanda Marjorie DE MESTRE · 2012 to 2026
$5.7M
Mechanisms of Nipah virus fusion and entryR01AI109022 · NIAID · WASHINGTON STATE UNIVERSITY · PI AGUILAR-CARRENO, HECTOR · 2014 to 2024
$4.3M
Molecular and cellular mechanism regulating innate immunity and inflammation during pattern recognition receptor activation and respiratory virus infectionR01AI083387 · NIAID · WASHINGTON STATE UNIVERSITY · PI BOSE, SANTANU · 2010 to 2021
$3.1M
Cornell Initiative for Maximizing Student DevelopmentR25GM125597 · NIGMS · CORNELL UNIVERSITY · PI AUGUST, AVERY · 2018 to 2022
$2.2M
Regulation of IL10 production in CD8+ T cells during Flu infection by tyrosine kinase ItkR01AI138570 · NIAID · CORNELL UNIVERSITY · PI AUGUST, AVERY · 2018 to 2022
$2.1M
Low pH-mediated HSV fusion and entryR01AI119159 · NIAID · WASHINGTON STATE UNIVERSITY · PI NICOLA, ANTHONY V · 2015 to 2019
$2.0M
Novel Sulfide Releasing Agents for Ischemic InjuryR01HL116571 · NHLBI · WASHINGTON STATE UNIVERSITY · PI LEFER, DAVID JOSEPH, XIAN, MING · 2014 to 2017
$1.8M
Itk mediated tuning of CD8+ memory T cell developmentR01AI120701 · NIAID · CORNELL UNIVERSITY · PI AUGUST, AVERY · 2016 to 2019
$1.5M
Immuno-Engineering: Integrated Engineering and Immunology TrainingT32EB023860 · NIBIB · CORNELL UNIVERSITY · PI AUGUST, AVERY, PUTNAM, DAVID A · 2018 to 2022
$933k
Mechanism of membrane inactivation method to prepare enveloped virus vaccinesR21AI156731 · NIAID · CORNELL UNIVERSITY · PI AGUILAR-CARRENO, HECTOR · 2021 to 2022
$444k
Viral and cellular mechanisms of HSV fusion and entryR56AI119159 · NIAID · WASHINGTON STATE UNIVERSITY · PI NICOLA, ANTHONY V · 2022 to 2022
$374k
NHLBI NIH HHS R01 HL116571NIAID NIH HHS R01 AI083387NIAID NIH HHS R01 AI109022NIAID NIH HHS R01 AI119159NIAID NIH HHS R01 AI120701NIAID NIH HHS R01 AI138570NIAID NIH HHS R21 AI156731NIAID NIH HHS R56 AI119159NIBIB NIH HHS T32 EB023860NIGMS NIH HHS R25 GM125597NIGMS NIH HHS T32 GM008336NIH HHS T32 OD011000
6 · The paper itself

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.

Indexed as

Antiviral AgentsInfluenza VaccinesOrthomyxoviridae InfectionsSulfurVaccine DevelopmentAnimalsAntibodies, NeutralizingAntibodies, ViralDogsFemaleHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza, HumanMadin Darby Canine Kidney CellsMiceMice, Inbred BALB CAntibodies, NeutralizingAntibodies, ViralAntiviral AgentsHemagglutinin Glycoproteins, Influenza VirusInfluenza VaccinesSulfurVaccines, Inactivated

Identifiers

PMID41495036
PMCPMC12847912

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.