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Conserved molecular signatures in the spike protein provide evidence indicating the origin of SARS-CoV-2 and a Pangolin-CoV (MP789) by recombination(s) between specific lineages of Sarbecoviruses
Author(s) -
Bijendra Khadka,
Radhey S. Gupta
Publication year - 2021
Publication title -
peerj
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.927
H-Index - 70
ISSN - 2167-8359
DOI - 10.7717/peerj.12434
Subject(s) - clade , biology , genetics , evolutionary biology , subgenus , lineage (genetic) , coronavirus , sequence alignment , covid-19 , phylogenetics , gene , peptide sequence , zoology , genus , medicine , disease , pathology , infectious disease (medical specialty)
Both SARS-CoV-2 and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus . To understand the origin of SARS-CoV-2, sequences for the spike and nucleocapsid proteins from sarbecoviruses were analyzed to identify molecular markers consisting of conserved inserts or deletions (termed CSIs) that are specific for either a particular clade of Sarbecovirus or are commonly shared by two or more clades of these viruses. Three novel CSIs in the N-terminal domain (NTD) of the spike protein S1-subunit (S1-NTD) are uniquely shared by SARS-CoV-2, Bat-CoV-RaTG13 and most pangolin CoVs (SARS-CoV-2r clade). Three other sarbecoviruses viz. bat-CoVZXC21, -CoVZC45 and -PrC31 (forming CoVZC/PrC31 clade), and a pangolin-CoV_MP789 also contain related CSIs in the same positions. In contrast to the S1-NTD, both SARS and SARS-CoV-2r viruses contain two large CSIs in the S1-C-terminal domain (S1-CTD) that are absent in the CoVZC/PrC31 clade. One of these CSIs, consisting of a 12 aa insert, is also present in the RShSTT clade (Cambodia-CoV strains). Sequence similarity studies show that the S1-NTD of SARS-CoV-2r viruses is most similar to the CoVZC/PrC31 clade, whereas their S1-CTD exhibits highest similarity to the RShSTT- (and the SARS-related) CoVs. Results from the shared presence of CSIs and sequence similarity studies on different CoV lineages support the inference that the SARS-CoV-2r cluster of viruses has originated by a genetic recombination between the S1-NTD of the CoVZC/PrC31 clade of CoVs and the S1-CTD of RShSTT/SARS viruses, respectively. We also present compelling evidence, based on the shared presence of CSIs and sequence similarity studies, that the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2 virus, has resulted from another independent recombination event involving the S1-NTD of the CoVZC/PrC31 CoVs and the S1-CTD of an unidentified SARS-CoV-2r related virus. The SARS-CoV-2 virus involved in this latter recombination event is postulated to be most similar to the SARS-CoV-2. Several other CSIs reported here are specific for other clusters of sarbecoviruses including a clade consisting of bat-SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mapping studies show that the identified CSIs form distinct loops/patches on the surface of the spike protein. It is hypothesized that these novel loops/patches on the spike protein, through their interactions with other host components, should play important roles in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for different clades of sarbecoviruses including SARS-CoV-2r clade provide novel means for the identification of these viruses and other potential applications.