ORF3a is one of the most important accessory proteins encoded by the genome of SARS-CoV-2. The major role of the ORF3a includes infectivity, virulence, morphogenesis, ion channel activity, and virus release. In the present study, globally reported higher frequency Q57H mutant showed significant conformational changes in ORF3a protein. The MD simulation analysis revealed that Q57H and Q57A mutants significantly change the structure, folding, and conformations in ORF3a protein. Non-bonding interaction analysis revealed that Q57H mutant formed a new hydrophobic interaction with Lys61 and Q57A mutant reduce H-bond interaction with Ser60 when compared to the wild type. The dynamic cross-correlation map analysis suggests that Q57H and Q57A mutant reduced both correlated and anti-correlated motions in SARS-CoV-2 ORF3a protein. Flexible residues motion in the dynamics is analyzed through principal component studies revealed that Q57H and Q57A mutants increase residual mobility in the TM2, TM3 and C-terminal domains. In summary, our findings are consistent with previous experimental reports and also provide detailed information on the structural basis of domains, which can assist in vaccine or therapeutic drugs developing against SARS-CoV-2.

Structure and dynamics of Q57H mutant in ORF3a investigated by molecular dynamics

ACS Fall 2021

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