PFKFB3-driven glycolysis determines virus replication and excessive inflammation

PFKFB3-driven glycolysis determines virus replication and excessive inflammation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article PFKFB3-driven glycolysis determines virus replication and excessive inflammation Shuofeng Yuan, Ronghui Liang, Yaoming Jin, Sihang Cao, Zi-Wei Ye, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6694201/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Novel interventions for 'delayed' presentation by patients with acute respiratory virus diseases are urgently needed to overcome the high viral burden and severe tissue inflammation. Glucose metabolism plays a central role in fueling virus replication and mediating inflammation and immunity. The host enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a critical engine that controls the rate of glycolysis. Viral components, such as Influenza A(H1N1) virus PB1 and SARS-CoV-2 Nsp1, can cause PFKFB3 SUMOylation to promote glycolysis, which may serve as a common mechanism to hijack host energy production. PFKFB3 SUMOylation also reprograms host bradykinin signaling with proinflammatory effect via its metabolite fructose 2,6-bisphosphate, which is independent of its proviral activity. Hospitalized flu patients exhibited higher plasma bradykinin than that of healthy donors. Therapy targeting PFKFB3 renders better mice protection than delayed oseltamivir treatment in vivo. Metabolic rewiring of PFKFB3-bradykinin axis can provide a combinatorial therapeutic target for mitigating viral replication and the associated tissue damage by a panel of respiratory viruses. Health sciences/Diseases/Infectious diseases/Viral infection Biological sciences/Microbiology/Virology/Virus–host interactions Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementarymaterials.pdf Supplementary materials Graphicabstract.tif Figure abstract Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6694201","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":461936867,"identity":"53e3616a-33fd-4832-a326-757a102f580d","order_by":0,"name":"Shuofeng 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