In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M<sup>pro</sup>) Inhibitors
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug le...
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MDPI AG
2021-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/7/2082 |
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| author | Mahmoud A. A. Ibrahim Alaa H. M. Abdelrahman Tarik A. Mohamed Mohamed A. M. Atia Montaser A. M. Al-Hammady Khlood A. A. Abdeljawaad Eman M. Elkady Mahmoud F. Moustafa Faris Alrumaihi Khaled S. Allemailem Hesham R. El-Seedi Paul W. Paré Thomas Efferth Mohamed-Elamir F. Hegazy |
| author_facet | Mahmoud A. A. Ibrahim Alaa H. M. Abdelrahman Tarik A. Mohamed Mohamed A. M. Atia Montaser A. M. Al-Hammady Khlood A. A. Abdeljawaad Eman M. Elkady Mahmoud F. Moustafa Faris Alrumaihi Khaled S. Allemailem Hesham R. El-Seedi Paul W. Paré Thomas Efferth Mohamed-Elamir F. Hegazy |
| author_sort | Mahmoud A. A. Ibrahim |
| collection | DOAJ |
| description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (M<sup>pro</sup>) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of <i>in silico</i> analyses, six terpenes demonstrated high potency as M<sup>pro</sup> inhibitors with Δ<i>G</i><sub>binding</sub> ≤ −40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 M<sup>pro</sup> than lopinavir over 100 ns with Δ<i>G</i><sub>binding</sub> values of −51.9 vs. −33.6 kcal/mol, respectively. Protein–protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components <i>BCL2L1</i>, <i>IL2</i>, and <i>PRKC</i>. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target–function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further <i>in vitro</i> and <i>in vivo</i> testing. |
| first_indexed | 2024-03-10T12:35:45Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:35:45Z |
| publishDate | 2021-04-01 |
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| spelling | doaj.art-6c010b4c3ef74c72acfe7cb2c013bde72023-11-21T14:16:55ZengMDPI AGMolecules1420-30492021-04-01267208210.3390/molecules26072082In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M<sup>pro</sup>) InhibitorsMahmoud A. A. Ibrahim0Alaa H. M. Abdelrahman1Tarik A. Mohamed2Mohamed A. M. Atia3Montaser A. M. Al-Hammady4Khlood A. A. Abdeljawaad5Eman M. Elkady6Mahmoud F. Moustafa7Faris Alrumaihi8Khaled S. Allemailem9Hesham R. El-Seedi10Paul W. Paré11Thomas Efferth12Mohamed-Elamir F. Hegazy13Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, EgyptComputational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, EgyptChemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, EgyptMolecular Genetics and Genome Mapping Laboratory, Genome Mapping Department, Agricultural Genetic Engineering Research Institute (AGERI), Agricultural Research Center (ARC), Giza 12619, EgyptNational Institute of Oceanography & Fisheries, NIOF, Cairo 11516, EgyptComputational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, EgyptNational Institute of Oceanography & Fisheries, NIOF, Cairo 11516, EgyptDepartment of Biology, College of Science, King Khalid University, Abha 9004, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, SwedenDepartment of Chemistry & Biochemistry, Texas Tech University, Lubbock, TX 79409, USADepartment of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, GermanyChemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, EgyptSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (M<sup>pro</sup>) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of <i>in silico</i> analyses, six terpenes demonstrated high potency as M<sup>pro</sup> inhibitors with Δ<i>G</i><sub>binding</sub> ≤ −40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 M<sup>pro</sup> than lopinavir over 100 ns with Δ<i>G</i><sub>binding</sub> values of −51.9 vs. −33.6 kcal/mol, respectively. Protein–protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components <i>BCL2L1</i>, <i>IL2</i>, and <i>PRKC</i>. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target–function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further <i>in vitro</i> and <i>in vivo</i> testing.https://www.mdpi.com/1420-3049/26/7/2082drug discoverymarine natural productsmolecular dockingmolecular dynamicsSARS-CoV-2 main proteasevirtual drug screening |
| spellingShingle | Mahmoud A. A. Ibrahim Alaa H. M. Abdelrahman Tarik A. Mohamed Mohamed A. M. Atia Montaser A. M. Al-Hammady Khlood A. A. Abdeljawaad Eman M. Elkady Mahmoud F. Moustafa Faris Alrumaihi Khaled S. Allemailem Hesham R. El-Seedi Paul W. Paré Thomas Efferth Mohamed-Elamir F. Hegazy In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M<sup>pro</sup>) Inhibitors Molecules drug discovery marine natural products molecular docking molecular dynamics SARS-CoV-2 main protease virtual drug screening |
| title | In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M<sup>pro</sup>) Inhibitors |
| title_full | In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M<sup>pro</sup>) Inhibitors |
| title_fullStr | In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M<sup>pro</sup>) Inhibitors |
| title_full_unstemmed | In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M<sup>pro</sup>) Inhibitors |
| title_short | In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M<sup>pro</sup>) Inhibitors |
| title_sort | in silico mining of terpenes from red sea invertebrates for sars cov 2 main protease m sup pro sup inhibitors |
| topic | drug discovery marine natural products molecular docking molecular dynamics SARS-CoV-2 main protease virtual drug screening |
| url | https://www.mdpi.com/1420-3049/26/7/2082 |
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