Cited by 13SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

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A novel structure-based approach for identification of vertebrate susceptibility to SARS-CoV-2: Implications for future surveillance programmes

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Kaushik, Rahul, Kumar, Naveen, Zhang, Kam Y.J., Srivastava, Pratiksha, Bhatia, Sandeep, Malik, Yashpal Singh·2022·Environmental Research

Published version of a preprint

Abstract

Understanding the origin of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a highly debatable and unresolved issue for scientific communities all over the world. Understanding the mechanism of virus entry to the host cells is crucial to deciphering the susceptibility profiles of animal species to SARS-CoV-2. The interaction of SARS-CoV-2 ligands (receptor-binding domain on spike protein) with its host cell receptor, angiotensin-converting enzyme 2 (ACE2), is a critical determinant of host range and cross-species transmission. In this study, we developed and implemented a rigorous computational approach for predicting binding affinity between 299 ACE2 orthologs from diverse vertebrate species and the SARS-CoV-2 spike protein. The findings show that the SARS-CoV-2 spike protein can bind to a wide range of vertebrate species carrying evolutionary divergent ACE2, implying a broad host range at the virus entry level, which may contribute to cross-species transmission and further viral evolution. Furthermore, the current study facilitated the identification of genetic determinants that may differentiate susceptible from resistant host species based on the conservation of ACE2-spike protein interacting residues in vertebrate host species known to facilitate SARS-CoV-2 infection; however, these genetic determinants warrant in vivo experimental confirmation. The molecular interactions associated with varied binding affinity of distinct ACE2 isoforms in a specific bat species were identified using protein structure analysis, implying the existence of diversified bat species' susceptibility to SARS-CoV-2. The current study's findings highlight the importance of intensive surveillance programmes aimed at identifying susceptible hosts, especially those with the potential to transmit zoonotic pathogens, in order to prevent future outbreaks.

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Metadata

Authors
Kaushik, R., Kumar, N., Zhang, K. Y. J., Srivastava, P., Bhatia, S., & Malik, Y. S.
Affiliations
  • RIKEN (JP)
  • National Institute of High Security Animal Diseases (IN)
  • Guru Angad Dev Veterinary and Animal Sciences University (IN)
Corresponding author
Malik, Yashpal Singh
Venue
Environmental Research
Publisher
Elsevier BV
Published
2022-09
Volume
212
Issue
Pt C
Pages
113303
ISSN
0013-9351 (ISSN-L)
OpenAlex
W4225606090
Cited by
13
References
3
Citations by year
2026: 4 · 2024: 4 · 2023: 3 · 2022: 2
FWCI
1.10
Type
journal article
Language
en
Open access
Locations
  • Environmental Research (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • ICAR - National Agricultural Science Fund (NASF/ABA-8028/2020-21)
  • Japan Society for the Promotion of Science (18H02395)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
SARS-CoV-2, ACE2, spike protein, host range, interspecies transmission, binding affinity prediction, zoonotic pathogens, receptor binding domain
MeSH terms
Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Humans, Peptidyl-Dipeptidase A, Vertebrates, Spike Glycoprotein, Coronavirus

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