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. 2020 May 7;13(9):2168-2178.
doi: 10.1111/eva.12980. eCollection 2020 Oct.

SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability

Vinicio Armijos-Jaramillo  1 , Justin Yeager  2 , Claire Muslin  3 , Yunierkis Perez-Castillo  4
Affiliations

SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability

Vinicio Armijos-Jaramillo et al. Evol Appl. .

Abstract

The emergence of SARS-CoV-2 has resulted in nearly 1,280,000 infections and 73,000 deaths globally so far. This novel virus acquired the ability to infect human cells using the SARS-CoV cell receptor hACE2. Because of this, it is essential to improve our understanding of the evolutionary dynamics surrounding the SARS-CoV-2 hACE2 interaction. One way theory predicts selection pressures should shape viral evolution is to enhance binding with host cells. We first assessed evolutionary dynamics in select betacoronavirus spike protein genes to predict whether these genomic regions are under directional or purifying selection between divergent viral lineages, at various scales of relatedness. With this analysis, we determine a region inside the receptor-binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein and its union with human receptor ACE2. Next, to gain further insights into factors associated with recognition of the human host receptor, we performed modeling studies of five different betacoronaviruses and their potential binding to hACE2. Modeling results indicate that interfering with the salt bridges at hot spot 353 could be an effective strategy for inhibiting binding, and hence for the prevention of SARS-CoV-2 infections. We also propose that a glycine residue at the receptor-binding domain of the spike glycoprotein can have a critical role in permitting bat SARS-related coronaviruses to infect human cells.

Keywords: ACE2; SARS‐CoV‐2; coronavirus; molecular dynamics; positive selection; purifying selection; spike protein.

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Conflict of interest statement

None declared.

Figures

FIGURE 1
FIGURE 1
Phylogenetic tree of S‐protein genes of selected betacoronaviruses (“closer” dataset). Predicted nodes under episodic diversifying selection (according to predictions generated by aBSREL of HyPhy) were colored in blue. Numbers in the inner nodes represent the number of nonparametric bootstrap replicates
FIGURE 2
FIGURE 2
Plots of the total energy of the investigated RBDs‐hACE2 complexes along the 10 ns production MD simulations. Energy values are separately presented for ligands, receptors, and complexes
FIGURE 3
FIGURE 3
Predicted interaction of SARS2 (top), SARS2‐MUT (middle) and SARS (bottom) with the human ACE2 receptor. hACE2 in depicted in gray and the RBD of coronaviruses in cyan. Oxygen atoms are colored red and nitrogen blue. The numbering of the residues corresponds to that of the sequence of each spike glycoprotein
See this image and copyright information in PMC

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