Structural Evaluation and Interaction of Spike Protein of SARS-COV-2 with Different Proteins of Homo Sapiens: A Perspective to Evaluate the Hidden Pathology

Abstract

The SARS-CoV-2 epidemic, which caused widespread COVID-19, resulted in one of the most rogue pandemics in current history. It has also brought an unprecedented loss to the socio- economic stability. The pathogenesis of coronavirus disease 2019 (COVID-19) is primarily dependent on the underlying mechanisms that facilitate the entry of SARS-CoV-2 into host cells. ACE2 which is reported as a major receptor for the SARS-CoV-2 spike protein alone cannot account for multi-organ tropism of SARS-CoV-2. Recent researches have revealed large number of potential cell entry regulators that appear to co-localize in cells and tissues and have made the entry mechanism more complex, thereby enhancing the infectivity. Therefore in our study we effectively identified a group of proteins that have been reported as potentially important for COVID-19 infection, and investigate the molecular interaction pattern of these proteins with Pakistani variant of Spike protein. Full-length Pakistani variant of spike protein was modeled using SWISS MODEL and docked against the 12 human proteins (ACE2, ANPEP, ASGR1, AXL, CD147, CTSL, CTSB, DPP4, FURIN, KREMEN1, TMPRSS2 and TMPRSS4) using HADDOCK (High Ambiguity Driven protein–protein DOCKing) server.The unavailable structure of the Human proteins were Modelled using trRosetta and MD simulations were run using GROMACS. The interaction pattern of Spike protein and their binding affinity were analyzed against all receptors. Our results shows that almost all the human proteins shows effective binding with Sars-CoV-2. The strength of these interaction might help in shortlisting the target proteins against SARS-CoV-2.