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Evolutionary Relationships and Sequence-Structure Determinants in Human SARS Coronavirus-2 Spike Proteins for Host Receptor Recognition

preprint
revised on 29.05.2020 and posted on 01.06.2020 by Lalitha Guruprasad
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 CoV and 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 two sequence motifs in the N-terminal domain; "MESEFR" and "SYLTPG" are specific to human SARS CoV-2 and pangolin SARS CoV. In the receptor binding domain (RBD), three sequence loops; VGGNY (loop 1), YQAGSTPC (loop 2), EGFNCY (loop 3) and a tethered disulfide bridge Cys480-Cys488 connecting loops 2 and 3 are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, pangolin, human host sources and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) and the pangolin SARS CoV genomes as closest to the recent novel human SARS CoV-2 genomes. The bat CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV-2.

Funding

No funding

History

Email Address of Submitting Author

lalitha.guruprasad@uohyd.ac.in

Institution

School of Chemistry, University of Hyderabad, Hyderabad

Country

India

ORCID For Submitting Author

0000-0003-1878-6446

Declaration of Conflict of Interest

No conflict of interest

Version Notes

SARS CoV-2, version-2

Exports