Computational Investigation of Increased Virulence and Pathogenesis of SARS-CoV-2 Lineage B.1.1.7
New variants of SARS-CoV-2 are being reported worldwide. World health organization has reported Alpha (B.1.1.7), Beta (B.1.351 ), Gamma (P.1), Delta (B.1.617.2) and Omicron(B.1.1.529) as the variants of concern. There are speculations that the variants might evade the host immune responses induced by currently available vaccines and develop resistance to drugs under consideration. The first step of viral infection in COVID-19, occurs through the interaction of the spike protein’s receptor-binding domain (RBD) with the peptidase domain of the human ACE-2 (hACE-2) receptor. This study aims to get a molecular-level understanding of the mechanism behind increased infection rate due to such mutations in these variants. We have computationally studied the spike protein interaction in both wild-type and B.1.1.7 variant with hACE-2 receptor using molecular dynamics and MM-GBSA based binding free energy calculations. The binding free energy difference shows that mutant variant of spike protein has increased binding affinity for the hACE-2 receptor (i.e. ∆∆G(N501Y, A570D) is in the range -7.2 to -7.6 kcal/mol) and the results were validated using Density functional theory. We demonstrate that with the use of state-of-the-art computational approaches, we can, in advance, predict the virulent nature of variants of SARS-CoV-2 and alert the world healthcare system.