The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection

Accepted/In Press date: 17 February 2023

Published date: 13 March 2023

Additional Information: Funding Information: We would like to thank all members of the Hiscox Laboratory and the Centre for Genome Research for supporting SARS-CoV-2/COVID-19 sequencing research and members of ISARIC4C consortia (https://isaric4c.net/about/authors/). The authors would like to thank J. Druce and M.G. Catton from the Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3000, Australia, for providing the SARS-CoV-2 isolate used in this study. We would like to thank Oliver Schwartz for the gift of ACE2-A549 cells. ISARIC4C Investigators Consortium Lead Investigator: J Kenneth Baillie. Chief Investigator: Malcolm G Semple. Co-Lead Investigator: Peter JM Openshaw. ISARIC Clinical Coordinator: Gail Carson. Co-Investigator: Beatrice Alex, Petros Andrikopoulos, et al. Funding Information: This work was funded by U.S. Food and Drug Administration Medical Countermeasures Initiative contract (75F40120C00085) to JAH with Co-Is, MWC, ADD, AD, DAM, MGS, and LT. The article reflects the views of the authors and does not represent the views or policies of the FDA. The NHP work was funded by the Coalition of Epidemic Preparedness Innovations (CEPI) and the Medical Research Council Project CV220-060, “Development of an NHP model of infection and ADE with COVID-19 (SARS-CoV-2) both awarded to MWC. This work was also supported by the MRC (MR/W005611/1) G2P-UK: A national virology consortium to address phenotypic consequences of SARS-CoV-2 genomic variation (co-Is ADD and JAH). JAH is also funded by the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity. The ISARIC4C sample collection and sequencing in this study was supported by grants from the Medical Research Council (grant MC_PC_19059), the National Institute for Health Research (NIHR; award CO-CIN-01), and the Medical Research Council (MRC; grant MC_PC_19059). JAH, MGS, MWC, and LT are supported by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with the UK Health Security Agency (UKHSA), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (award 200907). LT is supported by a Wellcome Trust fellowship [205228/Z/16/Z]. PD and JKB acknowledge Institute Strategic Programme grant (no. BB/P013740/1) from the BBSRC. Publisher Copyright: © 2023, The Author(s).

Keywords: COVID-19, Genetic Background, Genome, Viral, Humans, Mutation, Pandemics, SARS-CoV-2/genetics

Local EPrints ID: 477881

URI: http://eprints.soton.ac.uk/id/eprint/477881

DOI: doi:10.1186/s13059-023-02881-5

ISSN: 1465-6906

PURE UUID: 708a6cde-2ff7-44ef-b1c7-098d951764bb

ORCID for Ahilanandan Dushianthan: orcid.org/0000-0002-0165-3359

Date deposited: 15 Jun 2023 17:01

Last modified: 17 Mar 2024 03:51