Journal article
Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis
Science (American Association for the Advancement of Science), v 388(6748), peadq7597
15 May 2025
PMID: 40373132
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo-electron microscopy single-particle analysis and cryo-electron tomography, we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove. Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states, revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors. These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development.
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Details
- Title
- Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis
- Creators
- Ruchao Peng - University of PennsylvaniaXin Xu - University of PennsylvaniaBinod Nepal - Drexel UniversityYikang Gong - University of PennsylvaniaFenglin Li - University of PennsylvaniaMax B Ferretti - University of PennsylvaniaMingyang Zhou - University of PennsylvaniaKristen W Lynch - University of PennsylvaniaGeorge M Burslem - University of PennsylvaniaSandhya Kortagere - Drexel UniversityRonen Marmorstein - University of PennsylvaniaYi-Wei Chang - University of Pennsylvania
- Publication Details
- Science (American Association for the Advancement of Science), v 388(6748), peadq7597
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE; WASHINGTON
- Number of pages
- 18
- Grant note
- David and Lucile Packard Fellowship for Science and Engineering: 2019- 69645 Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease Program Award: 1022785 Pennsylvania Department of Health FY19 Health Research Formula Fund AwardMildred Cohn Distinguished Postdoctoral AwardNational Institutes of Health (NIH): R35GM118090 NIH: R01GM116961, AI125524, MCB210021P
This study received support from the David and Lucile Packard Fellowship for Science and Engineering, grant no. 2019- 69645 (Y.-W.C.); Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease Program Award, grant no. 1022785 (Y.-W.C.); Pennsylvania Department of Health FY19 Health Research Formula Fund Award (Y.-W.C.); a Mildred Cohn Distinguished Postdoctoral Award (R.P.); National Institutes of Health (NIH), grant no. R35GM118090 (R.M.); NIH grant no. R01GM116961 (S.K.); NIH grant no. AI125524 (K.W.L.); and Anton 2 Award, grant no. MCB210021P (S.K.).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001490057300009
- Scopus ID
- 2-s2.0-105005475268
- Other Identifier
- 991022053485104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Multidisciplinary Sciences