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.
