Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- 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
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- 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 < −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
Datenquelle: 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
Datenquelle: 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
Datenquelle: PubMed
- Beziehungen:
- Eigentum von