Genetic variations and drug repurposing provides key insights into the disruption of the SARS COV2
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) is mediated via the initial interaction of the virus’s spike (S-) protein with a human receptor protein called angiotensin-converting enzyme 2 (hACE2). Interference in this association can have immense therapeutic importance. We used an in-silico combinatorial approach involving homology-based protein modeling, protein-protein docking, binding energy estimation and virtual screening techniques to probe for genetic variations and drug molecules for disruption of the hACE2-CoV2 interaction. Our results identified Ser19Pro variation on hACE2 showed similar structural stability to the native protein while having a destabilizing effect in the hACE2(Ser19Pro)-S-protein complex. We also found several FDA-approved drug molecules that can potentially induce competition-mediated destabilization of the hACE2-CoV2 complex. In conclusion, these findings provide critical insights for intervention strategies targeting the pathogenicity of SARS-CoV-2.