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

10.26434/chemrxiv.12085083.v1 ◽

2020 ◽

Cited By ~ 1

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.

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

Molecular Informatics ◽

10.1002/minf.202000187 ◽

2021 ◽

Author(s):

Nemanja Djokovic ◽

Dusan Ruzic ◽

Teodora Djikic ◽

Sandra Cvijic ◽

Jelisaveta Ignjatovic ◽

...

Keyword(s):

In Silico ◽

Drug Repurposing ◽

Main Protease ◽

Potential Inhibitors

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Aminoglycosides as potential inhibitors of SARS-CoV-2 main protease: an in silico drug repurposing study on FDA-approved antiviral and anti-infection agents

Journal of Infection and Public Health ◽

10.1016/j.jiph.2021.01.016 ◽

2021 ◽

Vol 14 (5) ◽

pp. 611-619

Author(s):

Mohammad Z. Ahmed ◽

Qamar Zia ◽

Anzarul Haque ◽

Ali S. Alqahtani ◽

Omar M. Almarfadi ◽

...

Keyword(s):

In Silico ◽

Drug Repurposing ◽

Main Protease ◽

Potential Inhibitors

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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

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Molecular docking, binding mode analysis, molecular dynamics, and prediction of ADMET/toxicity properties of selective potential antiviral agents against SARS-CoV-2 main protease: an effort toward drug repurposing to combat COVID-19

Molecular Diversity ◽

10.1007/s11030-021-10188-5 ◽

2021 ◽

Author(s):

Himanshu Rai ◽

Atanu Barik ◽

Yash Pal Singh ◽

Akhil Suresh ◽

Lovejit Singh ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Antiviral Agents ◽

Drug Repurposing ◽

Binding Mode ◽

Mode Analysis ◽

Main Protease

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Antiretroviral Drug Activity and Potential for Pre-Exposure Prophylaxis Against COVID-19 and HIV Infection

10.26434/chemrxiv.12250199.v1 ◽

2020 ◽

Cited By ~ 3

Author(s):

Dennis C. Copertino Jr. ◽

Bruno Lima ◽

Rodrigo Duarte ◽

Timothy Wilkin ◽

Roy Gulick ◽

...

Keyword(s):

In Silico ◽

Antiretroviral Drugs ◽

Hiv Protease ◽

People Living With Hiv ◽

Hiv Protease Inhibitors ◽

Drug Candidates ◽

Main Protease ◽

Exposure Prophylaxis ◽

Living With Hiv

COVID-19 is the disease caused by SARS-CoV-2, and has led to over 250,000 deaths by May 2020. Urgent studies to identify new antiviral drugs, repurpose existing drugs, or identify those drugs that can specifically target the overactive immune response are ongoing around the world. Antiretroviral drugs (ARVs) have been tested in past human coronavirus infections, and also against SARS-CoV-2, but a recent clinical trial of lopinavir and ritonavir failed to show any clinical benefit in COVID-19 disease. However, anecdotal reports suggest either reduced infection or a course of milder COVID-19 disease in people living with HIV (PLWH) on ARVs. We hypothesized ARVs other than lopinavir and ritonavir might be responsible for such effects. Here, we used chemoinformatic analyses to predict which ARVs would bind and potentially inhibit the SARS-CoV-2 main protease or RNA-dependent RNA polymerase enzymes, and identified a number of ARVs which bind to SARS-CoV-2 enzymes in silico. Our study identified HIV nucleoside/nucleotide analogue reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, tenofovir, zidovudine), HIV protease inhibitors (ASC09, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) and an HIV pharmacokinetic booster (cobicistat), as drug candidates with effective in silico binding to one or both viral enzymes. Tenofovir and emtricitabine are FDA-approved as HIV pre-exposure prophylaxis (PrEP) and have an extensive safety profile of use in populations without HIV. Existing or new combinations of antiretroviral drugs could potentially prevent or ameliorate the course of COVID-19, if shown to inhibit SARS-CoV-2 in vitro and/or in clinical trials. Further studies are needed to establish the activity of ARVs for treatment or prevention of SARS-CoV-2 infection.

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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).

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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

Antiretroviral Drug Activity and Potential for Pre-Exposure Prophylaxis Against COVID-19 and HIV Infection

10.26434/chemrxiv.12250199 ◽

2020 ◽

Cited By ~ 1

Author(s):

Dennis C. Copertino Jr. ◽

Bruno Lima ◽

Rodrigo Duarte ◽

Timothy Wilkin ◽

Roy Gulick ◽

...

Keyword(s):

In Silico ◽

Antiretroviral Drugs ◽

Hiv Protease ◽

People Living With Hiv ◽

Hiv Protease Inhibitors ◽

Drug Candidates ◽

Main Protease ◽

Exposure Prophylaxis ◽

Living With Hiv

COVID-19 is the disease caused by SARS-CoV-2, and has led to over 250,000 deaths by May 2020. Urgent studies to identify new antiviral drugs, repurpose existing drugs, or identify those drugs that can specifically target the overactive immune response are ongoing around the world. Antiretroviral drugs (ARVs) have been tested in past human coronavirus infections, and also against SARS-CoV-2, but a recent clinical trial of lopinavir and ritonavir failed to show any clinical benefit in COVID-19 disease. However, anecdotal reports suggest either reduced infection or a course of milder COVID-19 disease in people living with HIV (PLWH) on ARVs. We hypothesized ARVs other than lopinavir and ritonavir might be responsible for such effects. Here, we used chemoinformatic analyses to predict which ARVs would bind and potentially inhibit the SARS-CoV-2 main protease or RNA-dependent RNA polymerase enzymes, and identified a number of ARVs which bind to SARS-CoV-2 enzymes in silico. Our study identified HIV nucleoside/nucleotide analogue reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, tenofovir, zidovudine), HIV protease inhibitors (ASC09, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) and an HIV pharmacokinetic booster (cobicistat), as drug candidates with effective in silico binding to one or both viral enzymes. Tenofovir and emtricitabine are FDA-approved as HIV pre-exposure prophylaxis (PrEP) and have an extensive safety profile of use in populations without HIV. Existing or new combinations of antiretroviral drugs could potentially prevent or ameliorate the course of COVID-19, if shown to inhibit SARS-CoV-2 in vitro and/or in clinical trials. Further studies are needed to establish the activity of ARVs for treatment or prevention of SARS-CoV-2 infection.

Download Full-text