Predicting mammalian species at risk of being infected by SARS-CoV-2 from an ACE2 perspective

Yulong Wei,Heba Farookhi,Xuhua Xia,Parisa Aris

doi:10.1038/s41598-020-80573-x

Abstract

SARS-CoV-2 can transmit efficiently in humans, but it is less clear which other mammals are at risk of being infected. SARS-CoV-2 encodes a Spike (S) protein that binds to human ACE2 receptor to mediate cell entry. A species with a human-like ACE2 receptor could therefore be at risk of being infected by SARS-CoV-2. We compared between 132 mammalian ACE2 genes and between 17 coronavirus S proteins. We showed that while global similarities reflected by whole ACE2 gene alignments are poor predictors of high-risk mammals, local similarities at key S protein-binding sites highlight several high-risk mammals that share good ACE2 homology with human. Bats are likely reservoirs of SARS-CoV-2, but there are other high-risk mammals that share better ACE2 homologies with human. Both SARS-CoV-2 and SARS-CoV are closely related to bat coronavirus. Yet, among host-specific coronaviruses infecting high-risk mammals, key ACE2-binding sites on S proteins share highest similarities between SARS-CoV-2 and Pangolin-CoV and between SARS-CoV and Civet-CoV. These results suggest that direct coronavirus transmission from bat to human is unlikely, and that rapid adaptation of a bat SARS-like coronavirus in different high-risk intermediate hosts could have allowed it to acquire distinct high binding potential between S protein and human-like ACE2 receptors.

Highlights

SARS-CoV-2 can transmit efficiently in humans, but it is less clear which other mammals are at risk of being infected
We found that key S protein sites in SARS-CoV are most conserved by Civet-CoV, whereas key S protein sites in SARS-CoV-2 are most conserved by Pangolin-CoV
Key binding sites on the human Angiotensin-converting enzyme 2 (ACE2) receptor are most conserved by primates species and variably conserved in selected species belonging to eight other mammalian orders

Summary

Introduction

SARS-CoV-2 can transmit efficiently in humans, but it is less clear which other mammals are at risk of being infected. Among host-specific coronaviruses infecting high-risk mammals, key ACE2-binding sites on S proteins share highest similarities between SARS-CoV-2 and Pangolin-CoV and between SARS-CoV and Civet-CoV. Mammals at high risk of SARS‐CoV‐2 infection should have human‐like ACE2 receptors at key S protein‐binding sites Both SARS-CoV and SARS-CoV-2 genomes encode a Spike (S) protein that binds to human Angiotensin-converting enzyme 2 (ACE2) receptor to mediate viral entry into the host cell[1,2,3,4,5,6]. Efficiently infected humans and palm civets but not rats, and introducing point mutations in the ACE2 gene variably affected the binding potential between ACE2 receptor and SARS-CoV S protein in these s pecies[4]. Gene mutation experiments[3,4] showed that the conservation of Lys[31] and Tyr[41] on α-helix 1, residues 82–84 in the vicinity of α-helix 3, and residues 353–357 on β-sheet 5 in human ACE2 receptor are crucial for SARS-CoV infectivity because their replacements weakened the binding potential between SARS-CoV S protein and ACE2 receptor

Methods

Results

Conclusion