tetano
Editor, Senior Moderator
Science
. 2025 May 15;388(6748):eadq7597.
doi: 10.1126/science.adq7597. Epub 2025 May 15. Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis
Ruchao Peng[SUP] #[/SUP][SUP] 1 2 [/SUP], Xin Xu[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Binod Nepal[SUP] 4 [/SUP], Yikang Gong[SUP] #[/SUP][SUP] 1 2 [/SUP], Fenglin Li[SUP] #[/SUP][SUP] 1 2 5 [/SUP], Max B Ferretti[SUP] 1 [/SUP], Mingyang Zhou[SUP] 1 2 3 [/SUP], Kristen W Lynch[SUP] 1 [/SUP], George M Burslem[SUP] 1 2 [/SUP], Sandhya Kortagere[SUP] 4 [/SUP], Ronen Marmorstein[SUP] 1 2 3 [/SUP], Yi-Wei Chang[SUP] 1 2 [/SUP]
Affiliations
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.
. 2025 May 15;388(6748):eadq7597.
doi: 10.1126/science.adq7597. Epub 2025 May 15. Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis
Ruchao Peng[SUP] #[/SUP][SUP] 1 2 [/SUP], Xin Xu[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Binod Nepal[SUP] 4 [/SUP], Yikang Gong[SUP] #[/SUP][SUP] 1 2 [/SUP], Fenglin Li[SUP] #[/SUP][SUP] 1 2 5 [/SUP], Max B Ferretti[SUP] 1 [/SUP], Mingyang Zhou[SUP] 1 2 3 [/SUP], Kristen W Lynch[SUP] 1 [/SUP], George M Burslem[SUP] 1 2 [/SUP], Sandhya Kortagere[SUP] 4 [/SUP], Ronen Marmorstein[SUP] 1 2 3 [/SUP], Yi-Wei Chang[SUP] 1 2 [/SUP]
Affiliations
- PMID: 40373132
- DOI: 10.1126/science.adq7597
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.