Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2
There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/20/6171 |
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| author | Amr El-Demerdash Afnan Hassan Tarek Mohamed Abd El-Aziz James D. Stockand Reem K. Arafa |
| author_facet | Amr El-Demerdash Afnan Hassan Tarek Mohamed Abd El-Aziz James D. Stockand Reem K. Arafa |
| author_sort | Amr El-Demerdash |
| collection | DOAJ |
| description | There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution of new viral variants, inconsistent availability of the vaccine around the world, and vaccine hesitancy, in some countries, makes it unreasonable to rely on mass vaccination alone to combat this pandemic. Consequently, much effort is directed to identifying potential antiviral treatments. Marine brominated tyrosine alkaloids are recognized to have antiviral potential. We test here the antiviral capacity of fourteen marine brominated tyrosine alkaloids against five different target proteins from SARS-CoV-2, including main protease (M<sup>pro</sup>) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H). These marine alkaloids, particularly the hexabrominated compound, fistularin-3, shows promising docking interactions with predicted binding affinities (S-score = −7.78, −7.65, −6.39, −6.28, −8.84 Kcal/mol) for the main protease (M<sup>pro</sup>) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H), respectively, where it forms better interactions with the protein pockets than the native interaction. It also shows promising molecular dynamics, pharmacokinetics, and toxicity profiles. As such, further exploration of the antiviral properties of fistularin-3 against SARS-CoV-2 is merited. |
| first_indexed | 2024-03-10T06:20:54Z |
| format | Article |
| id | doaj.art-37f7cf9bda324e25b67871e41736e42d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T06:20:54Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-37f7cf9bda324e25b67871e41736e42d2023-11-22T19:19:13ZengMDPI AGMolecules1420-30492021-10-012620617110.3390/molecules26206171Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2Amr El-Demerdash0Afnan Hassan1Tarek Mohamed Abd El-Aziz2James D. Stockand3Reem K. Arafa4Department of Metabolic Biology & Biological Chemistry, The John Innes Center, Norwich Research Park, Norwich NR4 7UH, UKDrug Design and Discovery Laboratory, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza 12578, EgyptZoology Department, Faculty of Science, Minia University, El-Minia 61519, EgyptDepartment of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USADrug Design and Discovery Laboratory, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza 12578, EgyptThere have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution of new viral variants, inconsistent availability of the vaccine around the world, and vaccine hesitancy, in some countries, makes it unreasonable to rely on mass vaccination alone to combat this pandemic. Consequently, much effort is directed to identifying potential antiviral treatments. Marine brominated tyrosine alkaloids are recognized to have antiviral potential. We test here the antiviral capacity of fourteen marine brominated tyrosine alkaloids against five different target proteins from SARS-CoV-2, including main protease (M<sup>pro</sup>) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H). These marine alkaloids, particularly the hexabrominated compound, fistularin-3, shows promising docking interactions with predicted binding affinities (S-score = −7.78, −7.65, −6.39, −6.28, −8.84 Kcal/mol) for the main protease (M<sup>pro</sup>) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H), respectively, where it forms better interactions with the protein pockets than the native interaction. It also shows promising molecular dynamics, pharmacokinetics, and toxicity profiles. As such, further exploration of the antiviral properties of fistularin-3 against SARS-CoV-2 is merited.https://www.mdpi.com/1420-3049/26/20/6171SARS-CoV-2virtual screeningmolecular dockingmolecular dynamics simulationADME/Toxbrominated tyrosine alkaloids |
| spellingShingle | Amr El-Demerdash Afnan Hassan Tarek Mohamed Abd El-Aziz James D. Stockand Reem K. Arafa Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2 Molecules SARS-CoV-2 virtual screening molecular docking molecular dynamics simulation ADME/Tox brominated tyrosine alkaloids |
| title | Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2 |
| title_full | Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2 |
| title_fullStr | Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2 |
| title_full_unstemmed | Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2 |
| title_short | Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2 |
| title_sort | marine brominated tyrosine alkaloids as promising inhibitors of sars cov 2 |
| topic | SARS-CoV-2 virtual screening molecular docking molecular dynamics simulation ADME/Tox brominated tyrosine alkaloids |
| url | https://www.mdpi.com/1420-3049/26/20/6171 |
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