Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected the lives and livelihood of millions of individuals around the world. It has mutated several times after its first inception, with an estimated two mutations occurring every month. Although we have been successful in developing vaccines against the virus, emergence of variants has enabled it to escape therapy. Few of the generated variants are also reported to be more infectious than the Wild-type. The World Health Organization (WHO) has prioritized the variants into Variants of Concern (VOC) and Variants of Interest (VOI) to focus on the variants that pose a threat to public health. In this study, we compare the structural and dynamic attributes of all the RBD/ACE2 complexes for the reported VOCs, namely, Alpha, Beta, Gamma, and Delta through atomistic simulations. Results indicated that the orientation and binding energies of the VOCs were different from the Wild-type. Specifically, we observed that the Receptor Binding Domain (RBD) in B.1.351 (Beta) and B.1.617.2 (Delta) underwent a relative rotation to make the complex more compact. Protein dynamics, however, show that their fluctuations were similar to the Wild-type. It was also reflected in the calculation of the total interaction energies. Overall, it was observed that electrostatic interactions play a major role in the formation of the complexes. Detailed residue level energetics revealed that the most prominent changes in interaction energies were seen particularly at the mutated residues which were present at RBD/ACE2 interface. We found that B.1.167.2 (Delta) is one of the most tightly bound variants of SARS-CoV-2 with dynamics similar to Wild-type. High binding affinity of RBD towards ACE2 is indicative of an increase in the viral infectivity. Therefore, the intrinsic details presented in this study would be useful for the design and development of effective therapeutic strategies for the emerging variants of the virus.
Competing Interest Statement
The authors have declared no competing interest.