Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates.

BioRxiv : the Preprint Server for Biology
J. DamasHarris A Lewin

Abstract

The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low. Only mammals fell into the medium to very high categories, and only catarrhine primates in the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (<0.1%) variants in 10/25 binding sites. In addition, we observed evide...Continue Reading

Citations

Oct 1, 2020·Scientific Reports·Yuan ZhaoXiaozhong Peng
Jun 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·W John KressPaul D N Hebert
Sep 26, 2020·Cell Death & Disease·Sara PlattoErnesto Carafoli
Oct 8, 2020·Critical Care : the Official Journal of the Critical Care Forum·Salleh N EhaidebAbderrezak Bouchama
Oct 3, 2020·Transboundary and Emerging Diseases·Júlia Vergara-AlertJoaquim Segalés
Oct 27, 2020·Frontiers in Microbiology·Jie ZhaoBao-Ping Tian
Nov 18, 2020·Biochemical and Biophysical Research Communications·Sara PlattoErnesto Carafoli
Jun 3, 2021·Pathogens·Lorena JemeršićDragan Brnić
Aug 14, 2020·Journal of Proteome Research·Michelle Heck, Benjamin A Neely

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Methods Mentioned

BETA
co-crystallization
glycosylation
transfection

Software Mentioned

UFBoot
Topmed
MODEL
Phylogenetic Analysis using Maximum Likelihood ( PAML
COBALT
ModelFinder
PhyloP
Clustal Omega
6MOJ
AUGUSTUS

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