Insights on the Structural Variations of the Furin-Like Cleavage Site Found Among the December 2019-July 2020 SARS-CoV-2 Spike Glycoprotein: A Computational Study Linking Viral Evolution and Infection

• Published in: Frontiers in medicine Vol. 8; p. 613412
• Main Authors: Cueno, Marni E, Ueno, Miu, Iguchi, Rinako, Harada, Tsubasa, Miki, Yoshifumi, Yasumaru, Kanae, Kiso, Natsumi, Wada, Kanta, Baba, Koki, Imai, Kenichi
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 10.03.2021
• Subjects: furin-like cleavage site; infection clusters; Medicine; SARS-CoV-2 (SARS2); spike glycoprotein; structural variations; SARS-CoV-2 (SARS2); furin-like cleavage site; spike glycoprotein; structural variations; infection clusters
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2021.613412

The SARS-CoV-2 (SARS2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic. One unique structural feature of the SARS2 spike protein is the presence of a furin-like cleavage site (FLC) which is associated with both viral pathogenesis and host tropism. Specifically, SARS2 spike protein binds to the host ACE-2 receptor which in-turn is cleaved by furin proteases at the FLC site, suggesting that SARS2 FLC structural variations may have an impact on viral infectivity. However, this has not yet been fully elucidated. This study designed and analyzed a COVID-19 genomic epidemiology network for December 2019 to July 2020, and subsequently generated and analyzed representative SARS2 spike protein models from significant node clusters within the network. To distinguish possible structural variations, a model quality assessment was performed before further protein model analyses and superimposition of the protein models, particularly in both the receptor-binding domain (RBD) and FLC. Mutant spike models were generated with the unique PRRA amino acid sequence found within the deleted FLC. We found 9 SARS2 FLC structural patterns that could potentially correspond to nine node clusters encompassing various countries found within the COVID-19 genomic epidemiology network. Similarly, we associated this with the rapid evolution of the SARS2 genome. Furthermore, we observed that either in the presence or absence of the unique PRRA amino acid sequence no structural changes occurred within the SARS2 RBD, which we believe would mean that the SARS2 FLC has no structural influence on SARS2 RBD and may explain why host tropism was maintained.