Evolutionary relationships and sequence-structure determinants in human SARS coronavirus-2 spike proteins for host receptor recognition.

Abstract

Coronavirus disease 2019 (COVID‐19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus‐2 (SARS CoV‐2). The SARS CoV‐2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV‐2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme‐2 (ACE‐2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV‐2 from various host sources in order to analyze the specificity in SARS CoV‐2 spike proteins required for causing infection in humans. Our results show that among the genomes analyzed, two sequence regions in the N‐terminal domain “MESEFR” and “SYLTPG” are specific to human SARS CoV‐2. In the receptor‐binding domain, two sequence regions “VGGNY“ and ”EIYQAGSTPCNGV” and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE‐2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources, and human SARS CoV‐2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV‐2 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression toward becoming human SARS CoV‐2.