21/04/1402
Characterization of SARS-CoV-2 omicron variants from Iran and evaluation of the effect of mutations on the spike, nucleocapsid, ORF8, and ORF9b proteins function
The SARS-CoV-2 Omicron strain, with 15 mutations in the
receptor binding domain (RBD), was detected in South Africa and rapidly
spread worldwide. SARS-CoV-2 ORF9b protein by binding to the
TOM70 receptor and ORF8 protein by binding to MHC-I, IF3 receptors
inhibit the hosts immune response. In this study, genomics variations
were evaluated for 96 samples isolated from Iran from March to July 2022
using the Nextclade web server and informatics tools. We identified the
mutations occurring in the SARS-CoV-2 proteins. We also
evaluated the effect of mutations on spike protein interaction with the
ACE2 receptor, ORF9b protein interaction with the TOM70 receptor, and
structural stability of ORF8 and nucleocapsid proteins using docking and
molecular dynamics. Results indicated that during March and April 2022,
the BA.2 strain was dominant in the south of Iran, while during June
2022, the BA.5 strain was dominant. BF.5 strain had the most divergence
among SARS-CoV-2 strains reported from south of Iran. The binding
affinity of BA.5 and BF.5 strains spike protein to ACE2 receptor is
similar, and compared to BA.2 strain, was stronger. The BF.5 ORF9b K40R
mutation causes a better binding affinity of the protein to the TOM70
receptor. Also, mutations that occurred in the ORF8 protein led to
instability in the dimer formation of this protein and improved immune
response for mutations that occurred in BA.2 strain, while this mutation
did not occur in BF.5 strain. The mutations that were detected in
nucleocapsid protein CTD and NTD domains caused the stability of these
domains.Communicated by Ramaswamy H. Sarma.