Author, as appears in the article.: Gimeno A; Mestres-Truyol J; Ojeda-Montes MJ; Macip G; Saldivar-Espinoza B; Cereto-Massagué A; Pujadas G; Garcia-Vallvé S

Department: Bioquímica i Biotecnologia

URV's Author/s: Cereto Massagué, Adrián José / Garcia Vallve, Santiago / Pujadas Anguiano, Gerard / Saldivar Espinoza, Bryan Percy

Keywords: Sars-cov-2 Sars coronavirus M-pro Covid-19 Chymotrypsin-like protease 3cl-pro 2019-ncov sars-cov-2 sars coronavirus m-pro covid-19 3cl-pro 2019-ncov

Abstract: Since the outbreak of the COVID-19 pandemic in December 2019 and its rapid spread worldwide, the scientific community has been under pressure to react and make progress in the development of an effective treatment against the virus responsible for the disease. Here, we implement an original virtual screening (VS) protocol for repositioning approved drugs in order to predict which of them could inhibit the main protease of the virus (M-pro), a key target for antiviral drugs given its essential role in the virus' replication. Two different libraries of approved drugs were docked against the structure of M-pro using Glide, FRED and AutoDock Vina, and only the equivalent high affinity binding modes predicted simultaneously by the three docking programs were considered to correspond to bioactive poses. In this way, we took advantage of the three sampling algorithms to generate hypothetic binding modes without relying on a single scoring function to rank the results. Seven possible SARS-CoV-2 M-pro inhibitors were predicted using this approach: Perampanel, Carprofen, Celecoxib, Alprazolam, Trovafloxacin, Sarafloxacin and ethyl biscoumacetate. Carprofen and Celecoxib have been selected by the COVID Moonshot initiative for in vitro testing; they show 3.97 and 11.90% M-pro inhibition at 50 µM, respectively.

Thematic Areas: Zootecnia / recursos pesqueiros Spectroscopy Saúde coletiva Química Psicología Physical and theoretical chemistry Organic chemistry Odontología Nutrição Molecular biology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Interdisciplinar Inorganic chemistry Geociências Farmacia Engenharias iv Engenharias ii Engenharias i Educação física Computer science applications Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Chemistry, multidisciplinary Catalysis Biotecnología Biodiversidade Biochemistry & molecular biology Astronomia / física

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 1422-0067

Author's mail: adrianjose.cereto@urv.cat gerard.pujadas@urv.cat santi.garcia-vallve@urv.cat adrianjose.cereto@urv.cat bryanpercy.saldivar@estudiants.urv.cat

Author identifier: 0000-0003-2598-8089 0000-0002-0348-7497 0000-0002-9667-2818

Record's date: 2023-04-01

Journal volume: 21

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.mdpi.com/1422-0067/21/11/3793

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: International Journal Of Molecular Sciences. 21 (11):

APA: Gimeno A; Mestres-Truyol J; Ojeda-Montes MJ; Macip G; Saldivar-Espinoza B; Cereto-Massagué A; Pujadas G; Garcia-Vallvé S (2020). Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition. International Journal Of Molecular Sciences, 21(11), -. DOI: 10.3390/ijms21113793

Article's DOI: 10.3390/ijms21113793

Entity: Universitat Rovira i Virgili

Journal publication year: 2020

First page: 3793

Publication Type: Journal Publications