An Integrative in Silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS‐CoV‐2 Main Protease

An in-silico drug repurposing study was carried out to search for potential COVID-19 antiviral agents. A dataset of 1615 FDA-approved drugs was docked in the active site of SARS CoV-2 Main protease. A subset of the top scoring hit compounds was subjected to follow-up molecular dynamics simulations to further characterise the predicted binding modes. The main findings are that the drugs Aliskiren, Capreomycin, Isovuconazonium, emerge as novel potential inhibitors. We also observed that Ceftolozane, Cobicistat, Carfilzomib and Saquinavir are well-ranked by our protocol, in agreement with other recent in silico drug repurposing studies, however MD simulations shows only potential for the three first, as Saquinavir exhibited an unstable binding mode. As many HIV-protease inhibitors has been reported as active and not active, Atazanavir and Lopinavir were included in the data set in order to rationalize the findings. In addition, our protocol ranked favourably Dronedarone suggesting that this recently reported SARS-CoV-2 inhibitor targets SARS-CoV-2 Main protease.

Download Full-text

Identification of Potential Inhibitors of SARS-CoV-2 Main Protease via a Rapid In-Silico Drug Repurposing Approach

10.26434/chemrxiv.12085083 ◽

2020 ◽

Author(s):

Cesar Mendoza-Martinez ◽

Alejandro Rodriguez-Lezama

Keyword(s):

In Silico ◽

Antiviral Agents ◽

Drug Repurposing ◽

Binding Mode ◽

Hiv Protease ◽

Hiv Protease Inhibitors ◽

Binding Modes ◽

Data Set ◽

Main Protease ◽

Potential Inhibitors

An in-silico drug repurposing study was carried out to search for potential COVID-19 antiviral agents. A dataset of 1615 FDA-approved drugs was docked in the active site of SARS CoV-2 Main protease. A subset of the top scoring hit compounds was subjected to follow-up molecular dynamics simulations to further characterise the predicted binding modes. The main findings are that the drugs Aliskiren, Capreomycin, Isovuconazonium, emerge as novel potential inhibitors. We also observed that Ceftolozane, Cobicistat, Carfilzomib and Saquinavir are well-ranked by our protocol, in agreement with other recent in silico drug repurposing studies, however MD simulations shows only potential for the three first, as Saquinavir exhibited an unstable binding mode. As many HIV-protease inhibitors has been reported as active and not active, Atazanavir and Lopinavir were included in the data set in order to rationalize the findings. In addition, our protocol ranked favourably Dronedarone suggesting that this recently reported SARS-CoV-2 inhibitor targets SARS-CoV-2 Main protease.

Download Full-text

In silico prediction of potential inhibitors for the main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing

Journal of Infection and Public Health ◽

10.1016/j.jiph.2020.06.016 ◽

2020 ◽

Vol 13 (9) ◽

pp. 1210-1223 ◽

Cited By ~ 32

Author(s):

Yogesh Kumar ◽

Harvijay Singh ◽

Chirag N. Patel

Keyword(s):

Molecular Docking ◽

In Silico ◽

Drug Repurposing ◽

Dynamics Simulation ◽

In Silico Prediction ◽

Main Protease ◽

Simulation Based ◽

Potential Inhibitors ◽

Molecular Docking And Dynamics

Download Full-text

In-Silico Drug Repurposing for Targeting SARS-CoV-2 Mpro

10.26434/chemrxiv.12210845 ◽

2020 ◽

Author(s):

Shilpa Sharma ◽

Shashank Deep

Keyword(s):

In Silico ◽

Drug Targets ◽

Md Simulation ◽

Chemical Constituents ◽

Drug Repurposing ◽

Viral Disease ◽

Ayurvedic Drugs ◽

Main Protease ◽

Novel Coronavirus ◽

Potential Inhibitors

COVID-19, caused by novel coronavirus or SARS-CoV-2, is a viral disease which has infected millions worldwide. Considering the urgent need of the drug for fighting against this infectious disease, we performed in-silico drug repurposing. The main protease (Mpro) is one of the best characterized drug targets among coronaviruses, therefore, this was screened for already known drugs, including chemical constituents of Ayurvedic drugs, using docking and MD simulation. The results suggest EGCG, withaferin A and artesunate may act as potential inhibitors of the main protease (Mpro).

Download Full-text

In-Silico Drug Repurposing for Targeting SARS-CoV-2 Mpro

10.26434/chemrxiv.12210845.v1 ◽

2020 ◽

Author(s):

Shilpa Sharma ◽

Shashank Deep

Keyword(s):

In Silico ◽

Drug Targets ◽

Md Simulation ◽

Chemical Constituents ◽

Drug Repurposing ◽

Viral Disease ◽

Ayurvedic Drugs ◽

Main Protease ◽

Novel Coronavirus ◽

Potential Inhibitors

COVID-19, caused by novel coronavirus or SARS-CoV-2, is a viral disease which has infected millions worldwide. Considering the urgent need of the drug for fighting against this infectious disease, we performed in-silico drug repurposing. The main protease (Mpro) is one of the best characterized drug targets among coronaviruses, therefore, this was screened for already known drugs, including chemical constituents of Ayurvedic drugs, using docking and MD simulation. The results suggest EGCG, withaferin A and artesunate may act as potential inhibitors of the main protease (Mpro).

Download Full-text

In silico investigation of potential inhibitors to main protease and spike protein of SARS-CoV-2 in propolis

Biochemistry and Biophysics Reports ◽

10.1016/j.bbrep.2021.100969 ◽

2021 ◽

pp. 100969

Author(s):

Azza H. Harisna ◽

Rizky Nurdiansyah ◽

Putri H. Syaifie ◽

Dwi W. Nugroho ◽

Kurniawan E. Saputro ◽

...

Keyword(s):

In Silico ◽

Spike Protein ◽

Main Protease ◽

Potential Inhibitors

Download Full-text

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel in Silico Method

10.26434/chemrxiv.12248561.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Milan Sencanski ◽

Vladimir Perovic ◽

Snezana Pajovic ◽

Miroslav Adzic ◽

Slobodan Paessler ◽

...

Keyword(s):

Protease Inhibitors ◽

In Silico ◽

Drug Target ◽

Transmission Rate ◽

Experimental Testing ◽

Drug Repurposing ◽

Global Public Health ◽

Main Protease ◽

Additional Approach ◽

Drugbank Database

The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening (VS) protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the ISM applied for Small Molecules was used for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing.

Download Full-text