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Blue Biotechnology : Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition
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- Ibrahim, Mahmoud A. A. (författare)
- Minia Univ, Fac Sci, Chem Dept, Computat Chem Lab, Al Minya 61519, Egypt.
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- Abdelrahman, Alaa H. M. (författare)
- Minia Univ, Fac Sci, Chem Dept, Computat Chem Lab, Al Minya 61519, Egypt.
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- Khalifa, Shaden A. M. (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden.
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- Mohamed, Tarik A. (författare)
- Qassim Univ, Coll Appl Med Sci, Dept Med Labs, Buraydah 51452, Saudi Arabia.
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- Moustafa, Mahmoud F. (författare)
- King Khalid Univ, Coll Sci, Dept Biol, Abha 9004, Saudi Arabia.;South Valley Univ, Fac Sci, Dept Bot & Microbiol, Qena 83523, Egypt.
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- Hakami, Abdulrahim R. (författare)
- King Khalid Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Abha 61481, Saudi Arabia.
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- Khalifa, Shaden A. M. (författare)
- Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden.
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- Alhumaydhi, Fahad A. (författare)
- Qassim Univ, Coll Appl Med Sci, Dept Med Labs, Buraydah 51452, Saudi Arabia.
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- Alrumaihi, Faris (författare)
- Qassim Univ, Coll Appl Med Sci, Dept Med Labs, Buraydah 51452, Saudi Arabia.
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- Abidi, Syed Hani (författare)
- Aga Khan Univ, Dept Biol & Biomed Sci, Karachi 74800, Pakistan.
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- Allemailem, Khaled S. (författare)
- Qassim Univ, Coll Appl Med Sci, Dept Med Labs, Buraydah 51452, Saudi Arabia.
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- Efferth, Thomas (författare)
- Johannes Gutenberg Univ Mainz, Inst Pharmaceut & Biomed Sci, Dept Pharmaceut Biol, Staudinger Weg 5, D-55128 Mainz, Germany.
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- Soliman, Mahmoud E. (författare)
- Univ KwaZulu Natal, Sch Hlth Sci, Mol Modelling & Drug Design Res Grp, ZA-4000 Durban, South Africa.
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- Pare, Paul W. (författare)
- Texas Tech Univ, Dept Chem & Biochem, Lubbock, TX 79409 USA.
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- El-Seedi, Hesham R. (författare)
- Uppsala universitet,Farmakognosi,Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt.;Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China.
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- Hegazy, Mohamed-Elamir F. (författare)
- Natl Res Ctr, Chem Med Plants Dept, 33 El Bohouth St, Giza 12622, Egypt.;Johannes Gutenberg Univ Mainz, Inst Pharmaceut & Biomed Sci, Dept Pharmaceut Biol, Staudinger Weg 5, D-55128 Mainz, Germany.
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- Atia, Mohamed A. M. (författare)
- Agr Res Ctr ARC, Agr Genet Engn Res Inst AGERI, Genome Mapping Dept, Mol Genet & Genome Mapping Lab, Giza 12619, Egypt.;Natl Res Ctr, Chem Med Plants Dept, 33 El Bohouth St, Giza 12622, Egypt.
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Minia Univ, Fac Sci, Chem Dept, Computat Chem Lab, Al Minya 61519, Egypt Institutionen för molekylär biovetenskap, Wenner-Grens institut (creator_code:org_t)
- 2021-07-13
- 2021
- Engelska.
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397. ; 19:7
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.mdpi.com...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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-pro) 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-pro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 M-pro 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-pro inhibitors with Delta G(binding) < -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 M-pro than darunavir with Delta G(binding) 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- genus Sarcophyton
- cembranoid diterpenes metabolites
- SARS-CoV-2 main protease
- molecular docking
- molecular dynamics
- reactome
Publikations- och innehållstyp
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- art (ämneskategori)
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Till lärosätets databas
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Ibrahim, Mahmoud ...
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Abdelrahman, Ala ...
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Khalifa, Shaden ...
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Mohamed, Tarik A ...
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Moustafa, Mahmou ...
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Hakami, Abdulrah ...
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visa fler...
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Alhumaydhi, Faha ...
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Alrumaihi, Faris
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Abidi, Syed Hani
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Allemailem, Khal ...
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Efferth, Thomas
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Soliman, Mahmoud ...
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Pare, Paul W.
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El-Seedi, Hesham ...
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Hegazy, Mohamed- ...
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Atia, Mohamed A. ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Infektionsmedici ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Farmaceutiska ve ...
- Artiklar i publikationen
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Marine Drugs
- Av lärosätet
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Uppsala universitet
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Stockholms universitet