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Manuscript_YK_HS-March30.pdf (4.74 MB)

In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

submitted on 31.03.2020, 02:07 and posted on 01.04.2020, 07:14 by Yogesh Kumar, Harvijay Singh
The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global
public health emergency of unprecedented level. Therefore the need of a drug or vaccine that
counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome
of SARS-CoV-2 is translated into large polyprotein which further processed into different
nonstructural proteins to form viral replication complex by virtue of virus specific proteases:
main protease (3-CL protease) and papain protease. This indispensable function of main protease
in virus replication makes this enzyme a promising target for the development of inhibitors and
potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide
ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.
has revealed the potential inhibitor binding mechanism and the determinants responsible for
involved molecular interactions. Here, we have carried out a virtual screening and molecular
docking study of FDA approved drugs primarily targeted for other viral infections, to investigate
their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral
drugs, top ten of which on the basis of their bending energy score are further examined through
molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir
and Raltegravir among others binds in the active site of the protease with similar or higher
affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug
molecules tested in this study, further needs to be corroborated by carrying out biochemical and
structural investigation. Moreover, this study advances the potential use of existing drugs to be
investigated and used to contain the rapidly expanding SARS-CoV-2 infection.




Email Address of Submitting Author


University of Minnesota


United States

ORCID For Submitting Author

Declaration of Conflict of Interest

No conflict of Interest