Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition

Publication type:
Journal article
Metadata:
Autoren
  • Mahmoud AA Ibrahim
  • Alaa HM Abdelrahman
  • Mohamed AM Atia
  • Tarik A Mohamed
  • Mahmoud F Moustafa
  • Abdulrahim R Hakami
  • Shaden AM Khalifa
  • Fahad A Alhumaydhi
  • Faris Alrumaihi
  • Syed Hani Abidi
  • Khaled S Allemailem
  • Thomas Efferth
  • Mahmoud E Soliman
  • Paul W Pare
  • Hesham R El-Seedi
  • Mohamed-Elamir F Hegazy
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000677354000001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3390/md19070391
eISSN
1660-3397
Externe Identifier
  • Clarivate Analytics Document Solution ID: TP1JI
  • PubMed Identifier: 34356816
Ausgabe der Veröffentlichung
7
Zeitschrift
MARINE DRUGS
Schlüsselwörter
  • genus Sarcophyton
  • cembranoid diterpenes metabolites
  • SARS-CoV-2 main protease
  • molecular docking
  • molecular dynamics
  • reactome
Artikelnummer
ARTN 391
Datum der Veröffentlichung
2021
Status
Published
Titel
Blue Biotechnology: Computational Screening of <i>Sarcophyton</i> Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition
Sub types
  • Article
Ausgabe der Zeitschrift
19

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:p>The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding &lt; −33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of −43.8 and −34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2.</jats:p>
Autoren
  • Mahmoud AA Ibrahim
  • Alaa HM Abdelrahman
  • Mohamed AM Atia
  • Tarik A Mohamed
  • Mahmoud F Moustafa
  • Abdulrahim R Hakami
  • Shaden AM Khalifa
  • Fahad A Alhumaydhi
  • Faris Alrumaihi
  • Syed Hani Abidi
  • Khaled S Allemailem
  • Thomas Efferth
  • Mahmoud E Soliman
  • Paul W Paré
  • Hesham R El-Seedi
  • Mohamed-Elamir F Hegazy
DOI
10.3390/md19070391
eISSN
1660-3397
Ausgabe der Veröffentlichung
7
Zeitschrift
Marine Drugs
Sprache
en
Online publication date
2021
Paginierung
391 - 391
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/md19070391
Datum der Datenerfassung
2021
Titel
Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition
Ausgabe der Zeitschrift
19

Data source: Crossref

Abstract
The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (M<sup>pro</sup>) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target M<sup>pro</sup>, a series of cembranoid diterpenes from the biologically active soft-coral genus <i>Sarcophyton</i> have been examined as SARS-CoV-2 M<sup>pro</sup> inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as M<sup>pro</sup> inhibitors with Δ<i>G</i><sub>binding</sub> < -33.0 kcal/mol. Binding energy and structural analyses of the most potent <i>Sarcophyton</i> inhibitor, bislatumlide A (<b>340</b>), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that <b>340</b> has a higher binding affinity against M<sup>pro</sup> than darunavir with Δ<i>G</i><sub>binding</sub> values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for <b>340</b>; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that <b>340</b> has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of <b>340</b> as an antiviral agent against SARS-CoV-2.
Addresses
  • Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt.
Autoren
  • Mahmoud AA Ibrahim
  • Alaa HM Abdelrahman
  • Mohamed AM Atia
  • Tarik A Mohamed
  • Mahmoud F Moustafa
  • Abdulrahim R Hakami
  • Shaden AM Khalifa
  • Fahad A Alhumaydhi
  • Faris Alrumaihi
  • Syed Hani Abidi
  • Khaled S Allemailem
  • Thomas Efferth
  • Mahmoud E Soliman
  • Paul W Paré
  • Hesham R El-Seedi
  • Mohamed-Elamir F Hegazy
DOI
10.3390/md19070391
eISSN
1660-3397
Externe Identifier
  • PubMed Identifier: 34356816
  • PubMed Central ID: PMC8308023
Funding acknowledgements
  • King Khalid University: R.G.P.1/143/42
  • Science and Technology Development Fund: 7972
  • Science and Technology Development Fund: 5480
Open access
true
ISSN
1660-3397
Ausgabe der Veröffentlichung
7
Zeitschrift
Marine drugs
Schlüsselwörter
  • Animals
  • Humans
  • Anthozoa
  • Diterpenes
  • Molecular Structure
  • Structure-Activity Relationship
  • Molecular Dynamics Simulation
  • Molecular Docking Simulation
  • COVID-19
  • SARS-CoV-2
  • Coronavirus 3C Proteases
  • Coronavirus Protease Inhibitors
  • COVID-19 Drug Treatment
Sprache
eng
Medium
Electronic
Online publication date
2021
Open access status
Open Access
Paginierung
391
Datum der Veröffentlichung
2021
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2021
Titel
Blue Biotechnology: Computational Screening of <i>Sarcophyton</i> Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition.
Sub types
  • Comparative Study
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
19

Files

https://www.mdpi.com/1660-3397/19/7/391/pdf?version=1626770474 https://europepmc.org/articles/PMC8308023?pdf=render

Data source: Europe PubMed Central

Abstract
The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding < -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2.
Date of acceptance
2021
Autoren
  • Mahmoud AA Ibrahim
  • Alaa HM Abdelrahman
  • Mohamed AM Atia
  • Tarik A Mohamed
  • Mahmoud F Moustafa
  • Abdulrahim R Hakami
  • Shaden AM Khalifa
  • Fahad A Alhumaydhi
  • Faris Alrumaihi
  • Syed Hani Abidi
  • Khaled S Allemailem
  • Thomas Efferth
  • Mahmoud E Soliman
  • Paul W Paré
  • Hesham R El-Seedi
  • Mohamed-Elamir F Hegazy
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/34356816
DOI
10.3390/md19070391
eISSN
1660-3397
Externe Identifier
  • PubMed Central ID: PMC8308023
Funding acknowledgements
  • Science and Technology Development Fund: 5480
  • Science and Technology Development Fund: 7972
  • King Khalid University: R.G.P.1/143/42
Ausgabe der Veröffentlichung
7
Zeitschrift
Mar Drugs
Schlüsselwörter
  • SARS-CoV-2 main protease
  • cembranoid diterpenes metabolites
  • genus Sarcophyton
  • molecular docking
  • molecular dynamics
  • reactome
  • Animals
  • Anthozoa
  • COVID-19
  • Coronavirus 3C Proteases
  • Coronavirus Protease Inhibitors
  • Diterpenes
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • SARS-CoV-2
  • Structure-Activity Relationship
  • COVID-19 Drug Treatment
Sprache
eng
Country
Switzerland
PII
md19070391
Datum der Veröffentlichung
2021
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Titel
Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition.
Sub types
  • Comparative Study
  • Journal Article
Ausgabe der Zeitschrift
19

Data source: PubMed

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