Affordable Access

deepdyve-link
Publisher Website

D155Y substitution of SARS-CoV-2 ORF3a weakens binding with Caveolin-1

Authors
  • Gupta, Suchetana
  • Mallick, Ditipriya
  • Banerjee, Kumarjeet
  • Mukherjee, Shrimon
  • Sarkar, Soumyadev
  • Lee, Sonny TM
  • Basuchowdhuri, Partha
  • Jana, Siddhartha S
Type
Published Article
Journal
Computational and Structural Biotechnology Journal
Publisher
Elsevier
Publication Date
Jan 31, 2022
Volume
20
Pages
766–778
Identifiers
DOI: 10.1016/j.csbj.2022.01.017
PMID: 35126886
PMCID: PMC8802530
Source
PubMed Central
Keywords
Disciplines
  • Research Article
License
Unknown

Abstract

The clinical manifestation of the recent pandemic COVID-19, caused by the novel SARS-CoV-2 virus, varies from mild to severe respiratory illness. Although environmental, demographic and co-morbidity factors have an impact on the severity of the disease, contribution of the mutations in each of the viral genes towards the degree of severity needs a deeper understanding for designing a better therapeutic approach against COVID-19. Open Reading Frame-3a (ORF3a) protein has been found to be mutated at several positions. In this work, we have studied the effect of one of the most frequently occurring mutants, D155Y of ORF3a protein, found in Indian COVID-19 patients. Using computational simulations we demonstrated that the substitution at 155th changed the amino acids involved in salt bridge formation, hydrogen-bond occupancy, interactome clusters, and the stability of the protein compared with the other substitutions found in Indian patients. Protein–protein docking using HADDOCK analysis revealed that substitution D155Y weakened the binding affinity of ORF3a with caveolin-1 compared with the other substitutions, suggesting its importance in the overall stability of ORF3a-caveolin-1 complex, which may modulate the virulence property of SARS-CoV-2.

Report this publication

Statistics

Seen <100 times