Can ACE2 receptor polymorphism predicts species susceptibility to SARS-CoV-2?

Abstract

A novel severe acute respiratory syndrome coronavirus named SARS-CoV-2, emerged in China in December 2019 and recently spread worldwide causing more than 144,987 deaths from COVID-19 disease. Similar to SARS-CoV that was related to a bat-borne coronavirus, this new virus originated from Rhinolophus affinis bats. Because bats usually transmit their coronaviruses to intermediate animal hosts that in turn represent a source of virus able to cross the species barrier to finally infect humans, the identification of an intermediate animal reservoir was recently the subject of intense researches. At the very beginning it was claimed that a reptile (Ophiophagus hannah) was the intermediate host. This hypothesis was quickly eliminated to be replaced by the pangolin (Manis javanica) hypothesis. Yet, several other animal species were recently reported as possible intermediate hosts in between bats and humans. To determine which intermediate animal host could have infected the index case patient with SARS-CoV-2, we used multi-sequence alignment, 3-D structure analysis and electrostatic potential surface generation of the angiotensin I converting enzyme 2 (ACE2) that serves as cellular receptor for SARS-CoV-2. We report evidence that such in silico investigation is a powerful tool that may help identification of potential SARS-CoV-2 susceptible species and that positions K31and Y41 in the a1 ridge, N82 and N90 in the loop and a3 and K353 in loop and b5 play a major role for SARS-CoV-2 binding to ACE2.

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

“…It is also absent on ACE2 from a number of species such as mouse or rat, which are considered resistant to infection, while it is present in species that have been shown to be susceptible to SARS-CoV-2 such as human, monkey, or cat ( Figure 2 ). This highlights the in silico approach as a simple screening tool to identify species susceptible to SARS-CoV-2 in a given ecosystem ( 74 , 86 – 88 ). SARS-CoV-2 infection was recently reported in mink farms and there is evidence that employees were infected with SARS-CoV-2 after minks became infected, suggesting that mink farms might become a reservoir for future spillover of SARS-CoV-2 to humans ( 73 ).…”

“…We thank Jean-Marc Rolain, Bernard Davoust, and Aurélie Caputo for stimulating discussions. A previous version of this paper, not peer-reviewed, has been made available online on Research Square since 28 April 2020, Devaux et al ( 86 ).…”

COVID-19: Time to exonerate the pangolin from the transmission of SARS-CoV-2 to humans

“…This opened the way for a whole series of in silico analyses of ACE2 polymorphism intended to predict which putative intermediate host animal might bear the ACE2 receptor best suited to capture a SARS-CoV-2-like Sarbecovirus transmissible to humans ( Liu et al, 2020a ; Shi et al, 2020 ; Lambert et al, 2020 ; Qiu et al, 2020 ; Luan et al, 2020 ; Zhao et al, 2020a , Zhao et al, 2020b ; Stawiski et al, 2020 ; Liu et al, 2020b ; Damas et al, 2020 ). Besides pangolin, SARS-CoV-2 was also reported to bind to ACE2 from Chinese horseshoe bats, civet, cat, turtle, ferret, monkey, dog, Chinese hamster, buffalo, cow, sheep, swine and even pigeon ( Liu et al, 2020a ; Shi et al, 2020 ; Lambert et al, 2020 ; Qiu et al, 2020 ; Luan et al, 2020 ; Zhao et al, 2020a , Zhao et al, 2020b ; Stawiski et al, 2020 ; Liu et al, 2020b ; Damas et al, 2020 ; Devaux et al, 2020 ). Nevertheless, the focus was put only on pangolin since it hosts Sarbecoviruses and is sold in wet markets.…”

“…1 a). These amino acid substitutions in ACE2 do not impact the global 3-D structure of the molecule even though they can alter the electrostatic potential surface of the molecule thereby affecting the affinity of the viral spike for ACE2 ( Devaux et al, 2020 ). The ACE2 receptors from three species of pangolin, i.e.…”

Expression of ACE2 receptor, soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin (1-7), is modulated in COVID-19 patients

“…During the past nine months, in vitro and in silico studies allowed to analyze interactions between SARS-CoV-2 and ACE2 (41)(42)(43). This has led many clinical research teams to hypothesize that soon after infection of people, SARS-CoV-2 is likely to trigger a dysregulation of ACE2 and subsequently AngII and Ang(1-7), contributing to worsening hypertension and releasing of proinflammatory cytokines, especially IL-6, thereby accelerating endothelial dysfunction and atherogenesis (34,44).…”