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In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors

BACKGROUND: The emergence of Coronavirus disease (COVID-19) has been declared a pandemic and made a medical emergency worldwide. Various attempts have been made, including optimizing effective treatments against the disease or developing a vaccine. Since the SARS-CoV-2 protease crystal structure has...

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Autores principales: Maulana, Saipul, Wahyuni, Tutik Sri, Widiyanti, Prihartini, Zubair, Muhammad Sulaiman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PAGEPress Publications, Pavia, Italy 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365649/
https://www.ncbi.nlm.nih.gov/pubmed/37492544
http://dx.doi.org/10.4081/jphia.2023.2508
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author Maulana, Saipul
Wahyuni, Tutik Sri
Widiyanti, Prihartini
Zubair, Muhammad Sulaiman
author_facet Maulana, Saipul
Wahyuni, Tutik Sri
Widiyanti, Prihartini
Zubair, Muhammad Sulaiman
author_sort Maulana, Saipul
collection PubMed
description BACKGROUND: The emergence of Coronavirus disease (COVID-19) has been declared a pandemic and made a medical emergency worldwide. Various attempts have been made, including optimizing effective treatments against the disease or developing a vaccine. Since the SARS-CoV-2 protease crystal structure has been discovered, searching for its inhibitors by in silico technique becomes possible. OBJECTIVE: This study aims to virtually screen the potential of phytoconstituents from the Begonia genus as 3Cl pro-SARS-CoV- 2 inhibitors, based on its crucial role in viral replication, hence making these proteases “promising” for the anti-SARS-CoV-2 target. METHODS: In silico screening was carried out by molecular docking on the web-based program DockThor and validated by a retrospective method. Predictive binding affinity (Dock Score) was used for scoring the compounds. Further molecular dynamics on Desmond was performed to assess the complex stability. RESULTS: Virtual screening protocol was valid with the area under curve value 0.913. Molecular docking revealed only β-sitosterol- 3-O-β-D-glucopyranoside with a lower docking score of - 9.712 kcal/mol than positive control of indinavir. The molecular dynamic study showed that the compound was stable for the first 30 ns simulations time with Root Mean Square Deviation <3 Å, despite minor fluctuations observed at the end of simulation times. Root Mean Square Fluctuation of catalytic sites HIS41 and CYS145 was 0.756 Å and 0.773 Å, respectively. CONCLUSIONS: This result suggests that β-sitosterol-3-O-β-Dglucopyranoside might be a prospective metabolite compound that can be developed as anti-SARS-CoV-2.
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spelling pubmed-103656492023-07-25 In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors Maulana, Saipul Wahyuni, Tutik Sri Widiyanti, Prihartini Zubair, Muhammad Sulaiman J Public Health Afr Article BACKGROUND: The emergence of Coronavirus disease (COVID-19) has been declared a pandemic and made a medical emergency worldwide. Various attempts have been made, including optimizing effective treatments against the disease or developing a vaccine. Since the SARS-CoV-2 protease crystal structure has been discovered, searching for its inhibitors by in silico technique becomes possible. OBJECTIVE: This study aims to virtually screen the potential of phytoconstituents from the Begonia genus as 3Cl pro-SARS-CoV- 2 inhibitors, based on its crucial role in viral replication, hence making these proteases “promising” for the anti-SARS-CoV-2 target. METHODS: In silico screening was carried out by molecular docking on the web-based program DockThor and validated by a retrospective method. Predictive binding affinity (Dock Score) was used for scoring the compounds. Further molecular dynamics on Desmond was performed to assess the complex stability. RESULTS: Virtual screening protocol was valid with the area under curve value 0.913. Molecular docking revealed only β-sitosterol- 3-O-β-D-glucopyranoside with a lower docking score of - 9.712 kcal/mol than positive control of indinavir. The molecular dynamic study showed that the compound was stable for the first 30 ns simulations time with Root Mean Square Deviation <3 Å, despite minor fluctuations observed at the end of simulation times. Root Mean Square Fluctuation of catalytic sites HIS41 and CYS145 was 0.756 Å and 0.773 Å, respectively. CONCLUSIONS: This result suggests that β-sitosterol-3-O-β-Dglucopyranoside might be a prospective metabolite compound that can be developed as anti-SARS-CoV-2. PAGEPress Publications, Pavia, Italy 2023-03-16 /pmc/articles/PMC10365649/ /pubmed/37492544 http://dx.doi.org/10.4081/jphia.2023.2508 Text en ©Copyright: the Author(s) https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Maulana, Saipul
Wahyuni, Tutik Sri
Widiyanti, Prihartini
Zubair, Muhammad Sulaiman
In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors
title In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors
title_full In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors
title_fullStr In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors
title_full_unstemmed In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors
title_short In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors
title_sort in silico screening of potential compounds from begonia genus as 3cl protease (3cl pro) sars-cov-2 inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365649/
https://www.ncbi.nlm.nih.gov/pubmed/37492544
http://dx.doi.org/10.4081/jphia.2023.2508
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