Inhibitory effects of 190 compounds against SARS-CoV-2 Mpro protein: Molecular docking interactions

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Gabriella B Souza
  • Larissa Sens
  • Stefan J Hammerschmidt
  • Natalia F de Sousa
  • Maryelle AG de Carvalho
  • Carlos VD Dos Santos
  • Tiago Tizziani
  • Monalisa A Moreira
  • Luiz AE Pollo
  • Erlon F Martin
  • Jose SS Neto
  • Maique W Biavatti
  • Francisco F de Assis
  • Bonaventure T Ngadjui
  • Ingrid K Simo
  • Pantaleon Ambassa
  • Marcus T Scotti
  • Luciana Scotti
  • Antonio L Braga
  • Tanja Schirmeister
  • Louis P Sandjo
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000998805200001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1002/ardp.202300207
eISSN
1521-4184
Externe Identifier
  • Clarivate Analytics Document Solution ID: O2GH1
  • PubMed Identifier: 37255416
ISSN
0365-6233
Ausgabe der Veröffentlichung
8
Zeitschrift
ARCHIV DER PHARMAZIE
Schlüsselwörter
  • enzyme assays
  • molecular docking
  • natural products
  • SARS-CoV-2 M-pro
  • thiosemicarbazones
Datum der Veröffentlichung
2023
Status
Published
Titel
Inhibitory effects of 190 compounds against SARS-CoV-2 M<SUP>pr</SUP><SUP>o</SUP> protein: Molecular docking interactions
Sub types
  • Article
Ausgabe der Zeitschrift
356

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:title>Abstract</jats:title><jats:p>COVID‐19 has caused many deaths since the first outbreak in 2019. The burden on healthcare systems around the world has been reduced by the success of vaccines. However, population adherence and the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants are still challenging tasks to be affronted. In addition, the newly approved drug presents some limitations in terms of side effects and drug interference, highlighting the importance of searching for new antiviral agents against SARS‐CoV‐2. The SARS‐CoV‐2 main protease (M<jats:sup>pr</jats:sup><jats:sup>o</jats:sup>) represents a versatile target to search for new drug candidates due to its essential role in proteolytic activities responsible for the virus replication. In this work, a series of 190 compounds, composed of 27 natural ones and 163 synthetic compounds, were screened in vitro for their inhibitory effects against SARS‐CoV‐2 M<jats:sup>pro</jats:sup>. Twenty‐five compounds inhibited M<jats:sup>pro</jats:sup> with inhibitory constant values (<jats:italic>K</jats:italic><jats:sub>i</jats:sub>) between 23.2 and 241 µM. Among them, a thiosemicarbazone derivative was the most active compound. Molecular docking studies using Protein Data Bank ID 5RG1, 5RG2, and 5RG3 crystal structures of M<jats:sup>pro</jats:sup> revealed important interactions identified as hydrophobic, hydrogen bonding and steric interactions with amino acid residues in the active site cavity. Overall, our findings indicate the described thiosemicarbazones as good candidates to be further explored to develop antiviral leads against SARS‐CoV‐2. Moreover, the studies showed the importance of careful evaluation of test results to detect and exclude false‐positive findings.</jats:p>
Autoren
  • Gabriella B Souza
  • Larissa Sens
  • Stefan J Hammerschmidt
  • Natália F de Sousa
  • Maryelle AG de Carvalho
  • Carlos VD Dos Santos
  • Tiago Tizziani
  • Monalisa A Moreira
  • Luiz AE Pollo
  • Erlon F Martin
  • José SS Neto
  • Maique W Biavatti
  • Francisco F de Assis
  • Bonaventure T Ngadjui
  • Ingrid K Simo
  • Pantaléon Ambassa
  • Marcus T Scotti
  • Luciana Scotti
  • Antonio L Braga
  • Tanja Schirmeister
  • Louis P Sandjo
DOI
10.1002/ardp.202300207
eISSN
1521-4184
ISSN
0365-6233
Ausgabe der Veröffentlichung
8
Zeitschrift
Archiv der Pharmazie
Sprache
en
Online publication date
2023
Datum der Veröffentlichung
2023
Status
Published
Herausgeber
Wiley
Herausgeber URL
http://dx.doi.org/10.1002/ardp.202300207
Datum der Datenerfassung
2024
Titel
Inhibitory effects of 190 compounds against SARS‐CoV‐2 M<sup>pr</sup><sup>o</sup> protein: Molecular docking interactions
Ausgabe der Zeitschrift
356

Datenquelle: Crossref

Abstract
COVID-19 has caused many deaths since the first outbreak in 2019. The burden on healthcare systems around the world has been reduced by the success of vaccines. However, population adherence and the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are still challenging tasks to be affronted. In addition, the newly approved drug presents some limitations in terms of side effects and drug interference, highlighting the importance of searching for new antiviral agents against SARS-CoV-2. The SARS-CoV-2 main protease (M<sup>pr</sup> <sup>o</sup> ) represents a versatile target to search for new drug candidates due to its essential role in proteolytic activities responsible for the virus replication. In this work, a series of 190 compounds, composed of 27 natural ones and 163 synthetic compounds, were screened in vitro for their inhibitory effects against SARS-CoV-2 M<sup>pro</sup> . Twenty-five compounds inhibited M<sup>pro</sup> with inhibitory constant values (K<sub>i</sub> ) between 23.2 and 241 µM. Among them, a thiosemicarbazone derivative was the most active compound. Molecular docking studies using Protein Data Bank ID 5RG1, 5RG2, and 5RG3 crystal structures of M<sup>pro</sup> revealed important interactions identified as hydrophobic, hydrogen bonding and steric interactions with amino acid residues in the active site cavity. Overall, our findings indicate the described thiosemicarbazones as good candidates to be further explored to develop antiviral leads against SARS-CoV-2. Moreover, the studies showed the importance of careful evaluation of test results to detect and exclude false-positive findings.
Addresses
  • Department of Chemistry, CFM, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis, Santa Catarina, Brazil.
Autoren
  • Gabriella B Souza
  • Larissa Sens
  • Stefan J Hammerschmidt
  • Natália F de Sousa
  • Maryelle AG de Carvalho
  • Carlos VD Dos Santos
  • Tiago Tizziani
  • Monalisa A Moreira
  • Luiz AE Pollo
  • Erlon F Martin
  • José SS Neto
  • Maique W Biavatti
  • Francisco F de Assis
  • Bonaventure T Ngadjui
  • Ingrid K Simo
  • Pantaléon Ambassa
  • Marcus T Scotti
  • Luciana Scotti
  • Antonio L Braga
  • Tanja Schirmeister
  • Louis P Sandjo
DOI
10.1002/ardp.202300207
eISSN
1521-4184
Externe Identifier
  • PubMed Identifier: 37255416
Funding acknowledgements
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico:
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior:
Open access
false
ISSN
0365-6233
Ausgabe der Veröffentlichung
8
Zeitschrift
Archiv der Pharmazie
Schlüsselwörter
  • Humans
  • Protease Inhibitors
  • Antiviral Agents
  • Structure-Activity Relationship
  • Molecular Dynamics Simulation
  • Molecular Docking Simulation
  • COVID-19
  • SARS-CoV-2
Sprache
eng
Medium
Print-Electronic
Online publication date
2023
Paginierung
e2300207
Datum der Veröffentlichung
2023
Status
Published
Datum der Datenerfassung
2023
Titel
Inhibitory effects of 190 compounds against SARS-CoV-2 M<sup>pr</sup> <sup>o</sup> protein: Molecular docking interactions.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
356

Datenquelle: Europe PubMed Central

Abstract
COVID-19 has caused many deaths since the first outbreak in 2019. The burden on healthcare systems around the world has been reduced by the success of vaccines. However, population adherence and the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are still challenging tasks to be affronted. In addition, the newly approved drug presents some limitations in terms of side effects and drug interference, highlighting the importance of searching for new antiviral agents against SARS-CoV-2. The SARS-CoV-2 main protease (Mpr o ) represents a versatile target to search for new drug candidates due to its essential role in proteolytic activities responsible for the virus replication. In this work, a series of 190 compounds, composed of 27 natural ones and 163 synthetic compounds, were screened in vitro for their inhibitory effects against SARS-CoV-2 Mpro . Twenty-five compounds inhibited Mpro with inhibitory constant values (Ki ) between 23.2 and 241 µM. Among them, a thiosemicarbazone derivative was the most active compound. Molecular docking studies using Protein Data Bank ID 5RG1, 5RG2, and 5RG3 crystal structures of Mpro revealed important interactions identified as hydrophobic, hydrogen bonding and steric interactions with amino acid residues in the active site cavity. Overall, our findings indicate the described thiosemicarbazones as good candidates to be further explored to develop antiviral leads against SARS-CoV-2. Moreover, the studies showed the importance of careful evaluation of test results to detect and exclude false-positive findings.
Date of acceptance
2023
Autoren
  • Gabriella B Souza
  • Larissa Sens
  • Stefan J Hammerschmidt
  • Natália F de Sousa
  • Maryelle AG de Carvalho
  • Carlos VD Dos Santos
  • Tiago Tizziani
  • Monalisa A Moreira
  • Luiz AE Pollo
  • Erlon F Martin
  • José SS Neto
  • Maique W Biavatti
  • Francisco F de Assis
  • Bonaventure T Ngadjui
  • Ingrid K Simo
  • Pantaléon Ambassa
  • Marcus T Scotti
  • Luciana Scotti
  • Antonio L Braga
  • Tanja Schirmeister
  • Louis P Sandjo
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37255416
DOI
10.1002/ardp.202300207
eISSN
1521-4184
Funding acknowledgements
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior:
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico:
Ausgabe der Veröffentlichung
8
Zeitschrift
Arch Pharm (Weinheim)
Schlüsselwörter
  • SARS-CoV-2 Mpro
  • enzyme assays
  • molecular docking
  • natural products
  • thiosemicarbazones
  • Humans
  • SARS-CoV-2
  • Molecular Docking Simulation
  • COVID-19
  • Protease Inhibitors
  • Structure-Activity Relationship
  • Antiviral Agents
  • Molecular Dynamics Simulation
Sprache
eng
Country
Germany
Paginierung
e2300207
Datum der Veröffentlichung
2023
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Titel
Inhibitory effects of 190 compounds against SARS-CoV-2 Mpr o protein: Molecular docking interactions.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
356

Datenquelle: PubMed

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