Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs

• DOI: 10.1016/j.csbj.2021.01.006
• Publication Date: 2021-01-14T05:43:58Z
• Authors: Camila Pontes; Victoria Ruiz-Serra; Rosalba Lepore; Alfonso Valencia
• Keywords: Conserved sequence; Coevolution; Multiple sequence alignment

The recent emergence of the novel SARS-CoV-2 in China and its rapid spread human population has led to a public health crisis worldwide. Like SARS-CoV, horseshoe bats currently represent most likely candidate animal source for SARS-CoV-2. Yet, specific mechanisms cross-species transmission adaptation host remain unknown. Here we show that unsupervised analysis conservation patterns across β-CoV spike protein family, using sequence information alone, can provide valuable insights on molecular basis specificity β-CoVs different cell receptors. More precisely, our results indicate receptor usage is encoded amino acid sequences CoV proteins form set determining positions (SDPs). Furthermore, by integrating structural data, silico mutagenesis coevolution could elucidate role SDPs mediating ACE2 binding Sarbecovirus lineage, either engaging through direct intermolecular interactions or affecting local environment motif. Finally, coevolving mutations paired MSA were able identify key contacts occurring at spike-ACE2 interface. These effective mining evolutionary records held family help tracing behind evolution host-receptor circulating future β-CoVs.