A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors

Seri Jo; Luca Signorile; Suwon Kim; Mi Sun Kim; Oscar Huertas; Raúl Insa; Núria Reig; Dong Hae Shin

doi:10.3390/ijms23126468

A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors

Seri Jo, Luca Signorile, Suwon Kim, Mi Sun Kim, Oscar Huertas, Raúl Insa, Núria Reig, Dong Hae Shin

Department of Pharmaceutical Sciences

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

3 Scopus citations

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech’s Artificial Intelligence (AI) technology, SOM^AI PRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.

Original language	English
Article number	6468
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	12
DOIs	https://doi.org/10.3390/ijms23126468
State	Published - 1 Jun 2022

Bibliographical note

Funding Information:
Funding: This work was supported by the Basic Science Research Programs, 2018R1D1A1B07050781 to DHS and 2018R1D1A1B07050942 to MK, funded by the National Research Foundation of Korea grant granted by the Ministry of Education, Science, and Technology, Republic of Korea (MEST) and by the CDTI-Covid I+D program COI-20201129 to SOM Biotech, granted by the Ministry of Science and Innovation, Government of Spain.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

SARS-CoV-2 3CL protease
antiviral
drug repurposing
fret
inhibitory compounds

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10.3390/ijms23126468

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title = "A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors",

abstract = "The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech{\textquoteright}s Artificial Intelligence (AI) technology, SOMAI PRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.",

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author = "Seri Jo and Luca Signorile and Suwon Kim and Kim, {Mi Sun} and Oscar Huertas and Ra{\'u}l Insa and N{\'u}ria Reig and Shin, {Dong Hae}",

note = "Funding Information: Funding: This work was supported by the Basic Science Research Programs, 2018R1D1A1B07050781 to DHS and 2018R1D1A1B07050942 to MK, funded by the National Research Foundation of Korea grant granted by the Ministry of Education, Science, and Technology, Republic of Korea (MEST) and by the CDTI-Covid I+D program COI-20201129 to SOM Biotech, granted by the Ministry of Science and Innovation, Government of Spain. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors

Abstract

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Keywords

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