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An in-silico evaluation of COVID-19 main protease with clinically approved drugs

preprint
revised on 26.06.2020 and posted on 29.06.2020 by TACHOUA Wafa, KABRINE Mohamed, Mamona Mushtaq, Zaheer Ul-Haq

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 Mpro 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 Mpro 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 (3CLpro) of SARS-CoV-2.


History

Email Address of Submitting Author

wtachoua@yahoo.fr

Institution

Benyoucef Benkhedda University,

Country

Algeria

ORCID For Submitting Author

0000-0003-4017-0082

Declaration of Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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