<p></p><p>A novel strain
of coronavirus, namely, SARS-CoV-2 identified in Wuhan city of China in
December 2019, continues to spread at a rapid rate worldwide. There are no
specific therapies available and investigations regarding the treatment of this
disease are still lacking. In order to identify a novel potent inhibitor, we
performed blind docking studies on the main virus protease M<sup>pro</sup> with
eight approved drugs belonging to four pharmacological classes such as:
anti-malarial, anti-bacterial, anti-infective and anti-histamine. Among the
eight studied compounds, Lymecycline and Mizolastine appear as potential
inhibitors of this protease. When docked against M<sup>pro </sup>crystal
structure, these two compounds revealed a minimum binding energy of -8.87 and
-8.71 kcal/mol with 168 and 256 binding modes detected in the binding substrate
pocket, respectively. Further, to study the interaction mechanism and
conformational dynamics of protein-ligand complexes, Molecular dynamic
simulation and MM/PBSA
binding free calculations were performed. Our results showed that both Lymecycline and
Mizolastine bind in the active site. And exhibited good binding affinities
towards target protein. Moreover, the ADMET analysis also indicated
drug-likeness properties. Thus it is suggested that the identified compounds
can inhibit Chymotrypsin-like protease (3CL<sup>pro</sup>) of SARS-CoV-2. </p><br><p></p>