SARS-CoV-2 Spike Glycoprotein and ACE2 Interaction Reveals Modulation of Viral Entry in Wild and Domestic Animals.

Manas Ranjan Praharaj,Priyanka Garg,Ravi Kumar Gandham,Veerbhan Kesarwani,Subeer Majumdar,B P Mishra,Bina Mishra,G Sai Kumar,Shailesh Sharma,Raja Ishaq Nabi Khan,Trilochan Mohapatra,Neelam A Topno,Manjit Panigrahi,Raj Kumar Singh

doi:10.3389/fmed.2021.775572

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral pathogen causing life-threatening diseases in humans. Interaction between the spike protein of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) is a potential factor in the infectivity of a host. In this study, the interaction of SARS-CoV-2 spike protein with its receptor, ACE2, in different hosts was evaluated to predict the probability of viral entry. Phylogeny and alignment comparison of the ACE2 sequences did not lead to any meaningful conclusion on viral entry in different hosts. The binding ability between ACE2 and the spike protein was assessed to delineate several spike binding parameters of ACE2. A significant difference between the known infected and uninfected species was observed for six parameters. However, these parameters did not specifically categorize the Orders into infected or uninfected. Finally, a logistic regression model constructed using spike binding parameters of ACE2, revealed that in the mammalian class, most of the species of Carnivores, Artiodactyls, Perissodactyls, Pholidota, and Primates had a high probability of viral entry. However, among the Proboscidea, African elephants had a low probability of viral entry. Among rodents, hamsters were highly probable for viral entry with rats and mice having a medium to low probability. Rabbits have a high probability of viral entry. In Birds, ducks have a very low probability, while chickens seemed to have medium probability and turkey showed the highest probability of viral entry. The findings prompt us to closely follow certain species of animals for determining pathogenic insult by SARS-CoV-2 and for determining their ability to act as a carrier and/or disseminator.

Highlights

Three large-scale disease outbreaks during the past two decades, viz., severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and swine acute diarrhea syndrome (SADS) were caused by three zoonotic coronaviruses (CoVs)
The protein and DNA sequence lengths of angiotensin-converting enzyme 2 (ACE2) varied in different hosts (Supplementary Table 1)
The within-group mean distance, the parameter indicative of variability of nucleotide sequences within the group, was found to be minimum in Perrisodactyla followed by Primates and was maximum among the Galliformes followed by Chiroptera (Supplementary Table 2)

Summary

Introduction

Three large-scale disease outbreaks during the past two decades, viz., severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and swine acute diarrhea syndrome (SADS) were caused by three zoonotic coronaviruses (CoVs). 866 (2,519 MERS cases) human lives, respectively [1], while SADS devastated livestock production by causing fatal disease in pigs in 2017. Seventeen years after the first highly pathogenic human CoVs, SARS-COV-2 is devastating the world with 87,808,867 cases and 1,894,632 deaths (as on January 07, 2021) [5]. This outbreak was first identified in Wuhan City, Hubei Province, China, in December 2019 and notified by WHO on January 5, 2020. The disease has since been named as COVID-19 by WHO

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