Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?

Christian A Devaux,Lucile Pinault,Didier Raoult,Ikram Omar Osman

doi:10.3389/fpubh.2020.608765

Abstract

A novel severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China in December 2019 and spread worldwide, causing more than 1.3 million deaths in 11 months. Similar to the human SARS-CoV, SARS-CoV-2 shares strong sequence homologies with a sarbecovirus circulating in Rhinolophus affinis bats. Because bats are expected to be able to transmit their coronaviruses to intermediate animal hosts that in turn are a source of viruses able to cross species barriers and infect humans (so-called spillover model), the identification of an intermediate animal reservoir was the subject of intense researches. It was claimed that a reptile (Ophiophagus hannah) was the intermediate host. This hypothesis was quickly ruled out and replaced by the pangolin (Manis javanica) hypothesis. Yet, pangolin was also recently exonerated from SARS-CoV-2 transmission to humans, leaving other animal species as presumed guilty. Guided by the spillover model, several laboratories investigated in silico the species polymorphism of the angiotensin I converting enzyme 2 (ACE2) to find the best fits with the SARS-CoV-2 spike receptor-binding site. Following the same strategy, we used multi-sequence alignment, 3-D structure analysis, and electrostatic potential surface generation of ACE2 variants to predict their binding capacity to SARS-CoV-2. We report evidence that such simple in silico investigation is a powerful tool to quickly screen which species are potentially susceptible to SARS-CoV-2. However, possible receptor binding does not necessarily lead to successful replication in host. Therefore, we also discuss here the limitations of these in silico approaches in our quest on the origins of COVID-19 pandemic.

Highlights

The recent emergence of severe acute respiratory syndrome (SARS)-CoV-2, responsible for a respiratory disease named COVID-19 (Coronavirus Disease-2019), threatens public health [1,2,3,4]
The angiotensin I converting enzyme 2 (ACE2) sequences from other bat species living in various ecosystem and with various geographic distribution, show increased amino acids substitutions at positions considered to be required for viral S1 spike binding (e.g., D. rotundus with K31N, Y41, N82T, N90D, and K353N)
We found that the three ACE2 proteins from Myotis bats were characterized by K31N, Y41H, N82T, N90, and K353, suggesting that these species are unlikely to replicate SARS-CoV-2-like ancestor-related viruses

Summary

Introduction

The recent emergence of SARS-CoV-2, responsible for a respiratory disease named COVID-19 (Coronavirus Disease-2019), threatens public health [1,2,3,4]. SARS-CoV-2 is responsible for respiratory infections, frequently asymptomatic but sometimes progresses to pneumonia, which, in its most severe forms can lead to death. SARS-CoV-2 is spreading very rapidly worldwide, and since WHO has declared COVID-19 as pandemic, about 54.5 million people have been infected worldwide (https://coronavirus.jhu.edu/map.html; 16 November, 2020). The case fatality rate of COVID-19 (estimated about 3.29%) increases with age and the existence of underlying diseases [2, 3, 5]. Primary site of disease Other organs ACE2. HLA Class I HCoV-OC43 Upper respiratory tract Fang et al [6] reported that the most distinctive comorbidities

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Conclusion