Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes

Abstract

In December 2019, COVID-19 epidemic was described in Wuhan, China, and the infection has spread widely affecting hundreds of thousands. Herein, an effort was made to identify commercially available drugs in order to repurpose them against coronavirus by the means of structure-based virtual screening. In addition, ZINC15 library was used to identify novel leads against main proteases. Human TMPRSS2 3D structure was first generated using homology modeling approach. Our molecular docking study showed four potential inhibitors against Mpro enzyme, two available drugs (Talampicillin and Lurasidone) and two novel drug-like compounds (ZINC000000702323 and ZINC000012481889). Moreover, four promising inhibitors were identified against TMPRSS2; Rubitecan and Loprazolam drugs, and compounds ZINC000015988935 and ZINC000103558522. ADMET profile showed that the hits from our study are safe and drug-like compounds. Furthermore, molecular dynamic (MD) simulation and binding free energy calculation using the MM-PBSA method was performed to calculate the interaction energy of the top-ranked drugs.

SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: anin silicoperspective

“…(Doublie & Ellenberger, 1998;Elfiky, 2020a;Elfiky & Ismail, 2018). Several studies are suggesting the effectiveness of different anti-viral drugs and compounds against the coronavirus proteins (Aanouz et al, 2020;Boopathi et al, 2020;Elfiky & Azzam, 2020;Elmezayen et al, 2020;Enayatkhani et al, 2020;Gupta et al, 2020;Khan et al, 2020aKhan et al, , 2020bMuralidharan et al, 2020;Pant et al, 2020;Sarma et al, 2020).…”

A molecular modeling approach to identify effective antiviral phytochemicals against the main protease of SARS-CoV-2

“…The Main protease (Mpro) also known as 3-C like protease (3CLpro) received great attention because of its important role in post-translational processing of replicase polyproteins (Boopathi et al, 2020;Elmezayen et al, 2020;Khan, Jha, et al, 2020;Wang et al, 2016). The enzymatic activity of this protein leads to processing of viral polyproteins.…”

An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study

“…Due to diverse bioactivity and less toxicity, naturally occurring bioactive flavonoid molecules have also been screened for their potential therapeutic effects (Khaerunnisa et al, 2020;Thuy et al, 2020). Numerous reports to identify the potential inhibitors of novel coronavirus have recently been published using computational methods (Aanouz et al, 2020;Elmezayen et al, 2020;Gupta et al, 2020;Muralidharan et al, 2020;Sarma et al, 2020). The transcription of the genomic RNA inside the cell generates a polypeptide which is proteolytically cleaved by the main protease (M Pro which is also known as 3CL Pro or chymotrypsin-like protease) at 11 different sites to produce proteins necessary for the replication of the virus.…”