Structure-guided discovery approach identifies potential lead compounds targeting $ M^{pro} $ of SARS-CoV-2
Abstract The ongoing coronavirus disease 19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become fatal for the world with affected population crossing over 25 million in more than 217 countries, consequently declared a global pandemic by the World Health Organization. Unfortunately, neither specific prophylactic or therapeutic drugs nor vaccines are available. To address the unmet medical needs, we explored a strategy identifying new compounds targeting the main protease ($ M^{pro} $) of SARS-CoV-2. Targeting the SARS-CoV-2 $ M^{pro} $ crystal structure (PDB ID: 6LU7) a combination of in silico screening, molecular docking, and dynamic approaches, a set of 5000 compounds of the ZINC database were screened. As a result, we identified and ranked the top 20 compounds based on the scores of ligand-interaction, their drug-likeness properties, and their predicted antiviral efficacies. The prominent drug-like and potent inhibitory compounds are 2-[2-(2-aminoacetyl) aminoacetyl] amino-3-(4-hydroxyphenyl)-propanamide (ZINC000004762511), 6′-fluoroaristeromycin (ZINC000001483267) and cyclo (L-histidyl-L-histidyl) (ZINC000005116916) scaffolds. Further in vitro and in vivo validations are required to demonstrate anti-SARS-CoV-2 activities..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
VirusDisease - 31(2020), 4 vom: 11. Nov., Seite 549-553 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Elmessaoudi-Idrissi, Mohcine [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
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| Anmerkungen: |
© Indian Virological Society 2020 |
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| doi: |
10.1007/s13337-020-00627-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC2122115939 |
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| 245 | 1 | 0 | |a Structure-guided discovery approach identifies potential lead compounds targeting $ M^{pro} $ of SARS-CoV-2 |
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| 500 | |a © Indian Virological Society 2020 | ||
| 520 | |a Abstract The ongoing coronavirus disease 19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become fatal for the world with affected population crossing over 25 million in more than 217 countries, consequently declared a global pandemic by the World Health Organization. Unfortunately, neither specific prophylactic or therapeutic drugs nor vaccines are available. To address the unmet medical needs, we explored a strategy identifying new compounds targeting the main protease ($ M^{pro} $) of SARS-CoV-2. Targeting the SARS-CoV-2 $ M^{pro} $ crystal structure (PDB ID: 6LU7) a combination of in silico screening, molecular docking, and dynamic approaches, a set of 5000 compounds of the ZINC database were screened. As a result, we identified and ranked the top 20 compounds based on the scores of ligand-interaction, their drug-likeness properties, and their predicted antiviral efficacies. The prominent drug-like and potent inhibitory compounds are 2-[2-(2-aminoacetyl) aminoacetyl] amino-3-(4-hydroxyphenyl)-propanamide (ZINC000004762511), 6′-fluoroaristeromycin (ZINC000001483267) and cyclo (L-histidyl-L-histidyl) (ZINC000005116916) scaffolds. Further in vitro and in vivo validations are required to demonstrate anti-SARS-CoV-2 activities. | ||
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Therapy | |
| 650 | 4 | |a Protease | |
| 650 | 4 | |a Zinc | |
| 650 | 4 | |a Inhibitors | |
| 700 | 1 | |a Tsukiyama-Kohara, Kyoko |4 aut | |
| 700 | 1 | |a Nourlil, Jalal |4 aut | |
| 700 | 1 | |a Kettani, Anass |4 aut | |
| 700 | 1 | |a Windisch, Marc P. |4 aut | |
| 700 | 1 | |a Kohara, Michinori |4 aut | |
| 700 | 1 | |a Malik, Yashpal Singh |4 aut | |
| 700 | 1 | |a Dhama, Kuldeep |4 aut | |
| 700 | 1 | |a Benjelloun, Soumaya |4 aut | |
| 700 | 1 | |a Ezzikouri, Sayeh |0 (orcid)0000-0002-3982-6163 |4 aut | |
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| 773 | 1 | 8 | |g volume:31 |g year:2020 |g number:4 |g day:11 |g month:11 |g pages:549-553 |
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| 951 | |a AR | ||
| 952 | |d 31 |j 2020 |e 4 |b 11 |c 11 |h 549-553 | ||