AUTHOR=Cueno Marni E. , Ueno Miu , Iguchi Rinako , Harada Tsubasa , Miki Yoshifumi , Yasumaru Kanae , Kiso Natsumi , Wada Kanta , Baba Koki , Imai Kenichi 

TITLE=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

JOURNAL=Frontiers in Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.613412

DOI=10.3389/fmed.2021.613412

ISSN=2296-858X

ABSTRACT=SARS-CoV-2 (SARS2) is established to cause the coronavirus disease 2019 (COVID-19) pandemic. One unique structural feature of SARS2 spike protein is the presence of a furin-like cleavage site (FLC) which is associated to 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 was never fully elucidated. Here, we designed and analyzed the December, 2019-July, 2020 COVID-19 genomic epidemiology network. Subsequently, generated and analyzed representative SARS2 spike protein models from significant node clusters within the network. Model quality assessment was performed prior to further protein model analyses and superimposition of protein models was done in order to distinguish possible structural variations particularly in both the receptor binding domain (RBD) and FLC. Moreover, mutant spike models were generated with the unique 681PRRA684 amino acid sequence found within the FLC deleted. We found that there are 9 SARS2 FLC structural patterns which potentially could correspond to 9 node clusters encompassing various countries found within the COVID-19 genomic epidemiology network. Similarly, we associated this to the rapid evolution of the SARS2 genome. Furthermore, we observed that either in the presence or absence of the unique 681PRRA684 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.