All viruses undergo rapid mutations and adapt quickly to the countermeasures that the immune system creates against them. The SARS-CoV-2 of the COVID-19 pandemic is no exception here. Peak protein from mutant strain B.1.617, also commonly known as the “Indian variant”. It is a full-length protein, which is active in its native trimeric form, which is stabilized in LMNG detergent.
The outbreak of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) in December 2019 has caused a global pandemic. The rapid mutation rate of the virus has created alarming situations around the world and is being attributed to false negativity in RT-PCR tests. It has also increased the chances of reinfection and immune escape.
Recently, several lineages, namely B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta), and B.1.617.3 have caused rapid infection worldwide. To understand the biophysical perspective, we have performed molecular dynamics simulations of four different peak complexes (receptor binding domain) -hACE2, namely, wild type (WT), alpha variant (N501Y peak mutant), Kappa (L452R, E484Q), and Delta (L452R, T478K) and compared their dynamics, binding energy, and molecular interactions.
Our results show that the mutation has caused a significant increase in the binding energy between the peak and hACE2 in the Alpha and Kappa variants. In the case of Kappa and Delta variants, mutations in L452R, T478K, and E484Q increased stability and intrachain interactions in the peak protein, which may change the ability to neutralize antibodies to interact for these peak variants.
Furthermore, we found that the Alpha variant had increased hydrogen interaction with hACE2 Lys353 and more binding affinity compared to WT. The current study provides the biophysical basis for understanding the molecular mechanism and rationale for the increased transmissivity and infectivity of mutants compared to wild-type SARS-CoV-2.