The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat RaTG13.

Journal of Virology
Shufeng LiuTony T Wang

Abstract

Biochemical and structural analyses suggest that SARS-CoV-2 is well-adapted to infecting humans and the presence of four residues (PRRA) at the S1/S2 site within the spike (S) protein, which may lead to unexpected tissue or host tropism. Here we report that SARS-CoV-2 efficiently utilized ACE2 of 9 species to infect 293T cells. Similarly, pseudoviruses bearing S protein derived from either the bat RaTG13 or pangolin GX, two closely related animal coronaviruses, utilized ACE2 of a diverse range of animal species to gain entry. Removal of PRRA from SARS-CoV-2 S protein displayed distinct effects on pseudoviral entry into different cell types. Unexpectedly, insertion of PRRA into the RaTG13 S protein selectively abrogated the usage of horseshoe bat and pangolin ACE2 but enhanced the usage of mouse ACE2 by the relevant pseudovirus to enter cells. Together, our findings identified a previously unrecognized effect of the PRRA insert on SARS-CoV-2 and RaTG13 S proteins.ImportanceThe four-residue insert (PRRA) at the boundary between the S1and S2 subunits of SARS-CoV-2 has been widely recognized since day 1 for its role in SARS-CoV-2 S protein processing and activation. As this PRRA insert is unique to SARS-CoV-2 among group b betacoro...Continue Reading

References

Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jin ZhongFrancis V Chisari
Jul 21, 2012·Viruses·Sandrine BelouzardGary R Whittaker
Dec 3, 2014·Virus Research·Jean Kaoru Millet, Gary R Whittaker
Feb 13, 2016·Nature Reviews. Drug Discovery·Alimuddin ZumlaKwok-Yung Yuen
Sep 1, 2016·Annual Review of Virology·Fang Li
Nov 1, 2016·Journal of Virology·Kazuya ShiratoShutoku Matsuyama
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Mar 7, 2020·The Journal of Infection·Jiahao ZhangWenbao Qi
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Apr 1, 2020·Nature·Jian ShangFang Li
Apr 15, 2020·Nature Medicine·Kristian G AndersenRobert F Garry
Apr 15, 2020·Cell Host & Microbe·Xuping XiePei-Yong Shi
Apr 22, 2020·Emerging Infectious Diseases·Susanna K P LauPatrick C Y Woo
May 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jian ShangFang Li
Jul 9, 2020·BioRxiv : the Preprint Server for Biology·Huihui MouMichael Farzan
Jul 11, 2020·Nature Structural & Molecular Biology·Antoni G WrobelSteven J Gamblin
Jul 23, 2020·Science·Yongfei CaiBing Chen
Jul 23, 2020·Nature·Markus HoffmannStefan Pöhlmann
Jul 25, 2020·Life Science Alliance·Dorothea BestleEva Böttcher-Friebertshäuser

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