Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies

• DOI: 10.1038/s41467-021-27950-w
• Publication Date: 2022-01-11T11:02:51Z
• Authors: Jeremy R. Keown; Zihan Zhu; Loïc Carrique; Haitian Fan; Alexander P. Walker; Itziar Serna Martin; Els Pardon; Jan Steyaert; Ervin Fodor; Jonathan M. Grimes
• Keywords: Pandemic

Abstract Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central the replication cycle of influenza is viral RNA-dependent RNA polymerase which transcribes replicates genome. The undergoes conformational rearrangements interacts with host proteins perform these functions. Here we determine structure 1918 virus in transcriptase replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally functionally characterise binding single-domain nanobodies pandemic virus. Combining functional structural data identify five sites on are sensitive inhibition by nanobodies. propose that at either prevents from assuming particular or interactions factors. highly conserved across subtypes, suggesting as effective targets for potential antiviral development.