In Silico and In Vitro Inhibition of SARS-CoV-2 PLpro with Gramicidin D

Sara Protić; Nevena Kaličanin; Milan Sencanski; Olivera Prodanović; Jelena Milicevic; Vladimir Perovic; Slobodan Paessler; Radivoje Prodanović; Sanja Glisic

doi:10.3390/ijms24031955

In Silico and In Vitro Inhibition of SARS-CoV-2 PL^pro with Gramicidin D

Sara Protić, Nevena Kaličanin, Milan Sencanski, Olivera Prodanović, Jelena Milicevic, Vladimir Perovic, Slobodan Paessler, Radivoje Prodanović, Sanja Glisic

Pathology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrent pandemic. Since developing a new treatment takes a significant amount of time, drug repurposing can be an effective option for achieving a rapid response. This study used a combined in silico virtual screening protocol for candidate SARS-CoV-2 PL^pro inhibitors. The Drugbank database was searched first, using the Informational Spectrum Method for Small Molecules, followed by molecular docking. Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PL^pro. After the expression and purification of PL^pro, gramicidin D was screened for protease inhibition in vitro and was found to be active against PL^pro. The current study’s findings are significant because it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorable safety profile.

Original language	English (US)
Article number	1955
Journal	International journal of molecular sciences
Volume	24
Issue number	3
DOIs	https://doi.org/10.3390/ijms24031955
State	Published - Feb 2023

Keywords

COVID-19
PL
PL candidate inhibitor
anti SARS-CoV-2
gramicidin D

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

Access to Document

10.3390/ijms24031955

Cite this

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title = "In Silico and In Vitro Inhibition of SARS-CoV-2 PLpro with Gramicidin D",

abstract = "Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrent pandemic. Since developing a new treatment takes a significant amount of time, drug repurposing can be an effective option for achieving a rapid response. This study used a combined in silico virtual screening protocol for candidate SARS-CoV-2 PLpro inhibitors. The Drugbank database was searched first, using the Informational Spectrum Method for Small Molecules, followed by molecular docking. Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PLpro. After the expression and purification of PLpro, gramicidin D was screened for protease inhibition in vitro and was found to be active against PLpro. The current study{\textquoteright}s findings are significant because it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorable safety profile.",

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AU - Sencanski, Milan

AU - Prodanović, Olivera

AU - Milicevic, Jelena

AU - Perovic, Vladimir

AU - Paessler, Slobodan

AU - Prodanović, Radivoje

AU - Glisic, Sanja

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