Articles producció científica> Bioquímica i Biotecnologia

Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition

  • Identification data

    Identifier: imarina:6406029
    Authors:
    Gimeno AMestres-Truyol JOjeda-Montes MJMacip GSaldivar-Espinoza BCereto-Massagué APujadas GGarcia-Vallvé S
    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.
  • Others:

    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 / Macip Sancho, Guillem / OJEDA MONTES, Mª JOSÉ / 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 bryanpercy.saldivar@estudiants.urv.cat bryanpercy.saldivar@estudiants.urv.cat guillem.macip@estudiants.urv.cat guillem.macip@estudiants.urv.cat santi.garcia-vallve@urv.cat gerard.pujadas@urv.cat
    Author identifier: 0000-0002-9667-2818 0000-0002-9667-2818 0000-0002-0348-7497 0000-0003-2598-8089
    Record's date: 2024-10-12
    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: https://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
  • Keywords:

    Biochemistry & Molecular Biology,Catalysis,Chemistry, Multidisciplinary,Computer Science Applications,Inorganic Chemistry,Medicine (Miscellaneous),Molecular Biology,Organic Chemistry,Physical and Theoretical Chemistry,Spectroscopy
    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
    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
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