Computational analyses of the G476S variant of SARS-CoV-2: A focus on the interaction with human ACE-2 and neutralizing antibodies
Abstract Recently, several mutations in the SARS-CoV-2 genome have been identified and reported. However, little is currently known about the influence of these mutations on the infectivity, transmissibility and antigenicity of the virus. Here, using an integrative computational approach, we characterized the G476S variant of SARS-CoV-2 focusing on interactions with ACE-2 and neutralizing antibodies. The substitution of Gly-476 to Ser-476 in the SARS-CoV-2 Receptor-binding domain (RBD) largely affected the structural dynamics of the S-protein leading to significant influence on the interactions with ACE-2 and neutralizing antibodies. Structural properties of the S-protein such as conformation changes, residual fluctuations and residue surface area largely varied between the wild-type and G476S variant, especially in the RBD. Analyses of the interaction energies between S-protein and ACE-2 suggest that the G476S variant may have enhanced interactions with ACE-2 compared to the wild-type. The G476S variant was found to have weaker interactions with the neutralizing antibody H014 compared to the wild-type. Collectively, our findings have implications for the infectivity and antigenicity of the G476S variant of SARS-CoV-2.