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

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.

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

10.26434/chemrxiv.12248561.v2 ◽

2020 ◽

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.

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

Molecules ◽

10.3390/molecules25173830 ◽

2020 ◽

Vol 25 (17) ◽

pp. 3830 ◽

Cited By ~ 3

Author(s):

Milan Sencanski ◽

Vladimir Perovic ◽

Snezana B. Pajovic ◽

Miroslav Adzic ◽

Slobodan Paessler ◽

...

Keyword(s):

Protease Inhibitors ◽

In Silico ◽

Transmission Rate ◽

Experimental Testing ◽

Drug Repurposing ◽

Global Public Health ◽

Main Protease ◽

Screening Protocol ◽

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 protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the Informational spectrum method 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.

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Drug Repurposing for Candidate SARS-CoV-2 Papain-like protease (PLpro) Inhibitors by a combined in Silico Method

10.33774/chemrxiv-2021-39cd6 ◽

2021 ◽

Author(s):

Milan Sencanski ◽

Vladimir Perovic ◽

Jelena Milicevic ◽

Tamara Todorovic ◽

Radivoje Prodanovic ◽

...

Keyword(s):

In Silico ◽

Drug Target ◽

Experimental Testing ◽

Drug Repurposing ◽

Innate Immune ◽

Host Immune System ◽

In Silico Screening ◽

Safe Approach ◽

Very High ◽

Drugbank Database

The need for an effective drug against COVID-19, is, after almost 18 months since the global pandemics outburst, still very high. A very quick and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes vi-ral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and there-fore is an attractive drug target. In this study, we used a combined in silico virtual screening candidates for SARS-CoV-2 PLpro protease inhibitors. We used the Informational spectrum method applied for Small Molecules for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 44 drugs as potential SARS-CoV-2 PLpro inhibitors that we propose for further experimental testing.

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Identification of SARS-CoV-2 Papain-like protease (PLpro) inhibitors using combined computational approach

10.33774/chemrxiv-2021-39cd6-v2 ◽

2021 ◽

Author(s):

Milan Sencanski ◽

Vladimir Perovic ◽

Jelena Milicevic ◽

Tamara Todorovic ◽

Radivoje Prodanovic ◽

...

Keyword(s):

Small Molecules ◽

In Silico ◽

Drug Target ◽

Experimental Testing ◽

Drug Repurposing ◽

Innate Immune ◽

Host Immune System ◽

In Silico Screening ◽

Safe Approach ◽

Drugbank Database

In the current pandemic finding an effective drug to prevent or treat the infection is the highest priority. A rapid and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes viral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and therefore is an attractive drug target. In this study, we used a combined in silico virtual screening for candidates for SARS-CoV-2 PLpro protease inhibitors. We used the Informational spectrum method applied for Small Molecules for searching the Drugbank database followed by molecular docking. After in silico screening of drug space, we identified 44 drugs as potential SARS-CoV-2 PLpro inhibitors that we propose for further experimental testing.

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