<p></p><p>The current outbreak of the
corona virus disease 2019 (COVID-19), has affected almost entire world and
become pandemic now. Currently, there is neither any FDA approved drugs nor any
vaccines available to control it. Very recently in Bangladesh, a group of
doctors reported astounding success in treating patients suffering from
COVID-19 with two commonly used drugs, Ivermectin and Doxycycline. In the
current study we have explored the possible mechanism by which these drugs
might have worked for the positive response in the COVID-19 patients. To
explore the mechanism we have used molecular docking and molecular dynamics simulation
approach. Effectiveness of Ivermectin and doxycycline were evaluated against Main
Protease (Mpro), Spike (S) protein, Nucleocapsid (N), RNA-dependent RNA
polymerase (RdRp, NSP12), ADP Ribose Phosphatase (NSP3), Endoribonuclease
(NSP15) and methyltransferase (NSP10-NSP16 complex) of SARS-CoV-2 as well as human
angiotensin converting enzyme 2 (ACE2) receptor. Our study shows that both
Ivermectin and doxycycline have significantly bind with SARS-CoV-2 proteins but
Ivermectin was better binding than doxycycline. Ivermectin showed a perfect binding
site to the Spike-RBD and ACE2 interacting region indicating that it might be
interfering in the interaction of spike with ACE2 and preventing the viral entry
in to the host cells. Ivermectin also exhibited significant binding affinity
with different SARS-CoV-2 structural and non-structural proteins (NSPs) which
have diverse functions in virus life cycle. Significant binding of Ivermectin with
RdRp indicate its role in the inhibition of the viral replication and
ultimately impeding the multiplication of the virus. Ivermectin also possess
significant binding affinity with NSP3, NSP10, NSP15 and NSP16 which helps
virus in escaping from host immune system. Molecular dynamics simulation study
shows that binding of the Ivermectin with Mpro, Spike, NSP3, NSP16 and ACE2 was
quiet stable. Thus, our docking and simulation studies reveal that combination
of Ivermectin and doxycycline might be executing the effect by inhibition of viral
entry and enhance viral load clearance by targeting various viral functional
proteins.</p><p></p>