Eslam B Elkaeed, Bshra A Alsfouk, Tuqa H Ibrahim, Reem K Arafa, Hazem Elkady, Ibrahim M Ibrahim, Ibrahim H Eissa, Ahmed M Metwaly
{"title":"通过多阶段计算机辅助药物发现严重急性呼吸系统综合征冠状病毒2型RNA依赖性RNA聚合酶的潜在天然抑制剂。","authors":"Eslam B Elkaeed, Bshra A Alsfouk, Tuqa H Ibrahim, Reem K Arafa, Hazem Elkady, Ibrahim M Ibrahim, Ibrahim H Eissa, Ahmed M Metwaly","doi":"10.1177/13596535231199838","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic has led to significant loss of life and economic disruption worldwide. Currently, there are limited effective treatments available for this disease. SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp) has been identified as a potential target for drug development against COVID-19. Natural products have been shown to possess antiviral properties, making them a promising source for developing drugs against SARS-CoV-2.</p><p><strong>Objectives: </strong>The objective of this study is to identify the most effective natural inhibitors of SARS-CoV-2 RdRp among a set of 4924 African natural products using a multi-phase <i>in silico</i> approach.</p><p><strong>Methods: </strong>The study utilized remdesivir (RTP), the co-crystallized ligand of RdRp, as a starting point to select compounds that have the most similar chemical structures among the examined set of compounds. Molecular fingerprints and structure similarity studies were carried out in the first part of the study. The second part of the study included molecular docking against SARS-CoV-2 RdRp (PDB ID: 7BV2) and Molecular Dynamics (MD) simulations including the calculation of RMSD, RMSF, Rg, SASA, hydrogen bonding, and PLIP. Moreover, the calculations of Molecular mechanics with generalised Born and surface area solvation (MM-GBSA) Lennard-Jones and Columbic electrostatic interaction energies have been conducted. Additionally, <i>in silico</i> ADMET and toxicity studies were performed to examine the drug likeness degrees of the selected compounds.</p><p><strong>Results: </strong>Eight compounds were identified as the most effective natural inhibitors of SARS-CoV-2 RdRp. These compounds are kaempferol 3-galactoside, kaempferol 3-<i>O</i>-<i>β</i>-D-glucopyranoside, mangiferin methyl ether, luteolin 7-<i>O</i>-<i>β</i>-D-glucopyranoside, quercetin-<i>O</i>-<i>β</i>-D-3-glucopyranoside, 1-methoxy-3-indolylmethyl glucosinolate, naringenin, and asphodelin A 4'-<i>O</i>-<i>β</i>-D-glucopyranoside.</p><p><strong>Conclusion: </strong>The results of this study provide valuable information for the development of natural product-based drugs against COVID-19. However, the elected compounds should be further studied <i>in vitro</i> and <i>in vivo</i> to confirm their efficacy in treating COVID-19.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Computer-assisted drug discovery of potential natural inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase through a multi-phase <i>in silico</i> approach.\",\"authors\":\"Eslam B Elkaeed, Bshra A Alsfouk, Tuqa H Ibrahim, Reem K Arafa, Hazem Elkady, Ibrahim M Ibrahim, Ibrahim H Eissa, Ahmed M Metwaly\",\"doi\":\"10.1177/13596535231199838\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The COVID-19 pandemic has led to significant loss of life and economic disruption worldwide. Currently, there are limited effective treatments available for this disease. SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp) has been identified as a potential target for drug development against COVID-19. Natural products have been shown to possess antiviral properties, making them a promising source for developing drugs against SARS-CoV-2.</p><p><strong>Objectives: </strong>The objective of this study is to identify the most effective natural inhibitors of SARS-CoV-2 RdRp among a set of 4924 African natural products using a multi-phase <i>in silico</i> approach.</p><p><strong>Methods: </strong>The study utilized remdesivir (RTP), the co-crystallized ligand of RdRp, as a starting point to select compounds that have the most similar chemical structures among the examined set of compounds. Molecular fingerprints and structure similarity studies were carried out in the first part of the study. The second part of the study included molecular docking against SARS-CoV-2 RdRp (PDB ID: 7BV2) and Molecular Dynamics (MD) simulations including the calculation of RMSD, RMSF, Rg, SASA, hydrogen bonding, and PLIP. Moreover, the calculations of Molecular mechanics with generalised Born and surface area solvation (MM-GBSA) Lennard-Jones and Columbic electrostatic interaction energies have been conducted. Additionally, <i>in silico</i> ADMET and toxicity studies were performed to examine the drug likeness degrees of the selected compounds.</p><p><strong>Results: </strong>Eight compounds were identified as the most effective natural inhibitors of SARS-CoV-2 RdRp. These compounds are kaempferol 3-galactoside, kaempferol 3-<i>O</i>-<i>β</i>-D-glucopyranoside, mangiferin methyl ether, luteolin 7-<i>O</i>-<i>β</i>-D-glucopyranoside, quercetin-<i>O</i>-<i>β</i>-D-3-glucopyranoside, 1-methoxy-3-indolylmethyl glucosinolate, naringenin, and asphodelin A 4'-<i>O</i>-<i>β</i>-D-glucopyranoside.</p><p><strong>Conclusion: </strong>The results of this study provide valuable information for the development of natural product-based drugs against COVID-19. However, the elected compounds should be further studied <i>in vitro</i> and <i>in vivo</i> to confirm their efficacy in treating COVID-19.</p>\",\"PeriodicalId\":8364,\"journal\":{\"name\":\"Antiviral Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antiviral Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/13596535231199838\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antiviral Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/13596535231199838","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Computer-assisted drug discovery of potential natural inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase through a multi-phase in silico approach.
Background: The COVID-19 pandemic has led to significant loss of life and economic disruption worldwide. Currently, there are limited effective treatments available for this disease. SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp) has been identified as a potential target for drug development against COVID-19. Natural products have been shown to possess antiviral properties, making them a promising source for developing drugs against SARS-CoV-2.
Objectives: The objective of this study is to identify the most effective natural inhibitors of SARS-CoV-2 RdRp among a set of 4924 African natural products using a multi-phase in silico approach.
Methods: The study utilized remdesivir (RTP), the co-crystallized ligand of RdRp, as a starting point to select compounds that have the most similar chemical structures among the examined set of compounds. Molecular fingerprints and structure similarity studies were carried out in the first part of the study. The second part of the study included molecular docking against SARS-CoV-2 RdRp (PDB ID: 7BV2) and Molecular Dynamics (MD) simulations including the calculation of RMSD, RMSF, Rg, SASA, hydrogen bonding, and PLIP. Moreover, the calculations of Molecular mechanics with generalised Born and surface area solvation (MM-GBSA) Lennard-Jones and Columbic electrostatic interaction energies have been conducted. Additionally, in silico ADMET and toxicity studies were performed to examine the drug likeness degrees of the selected compounds.
Results: Eight compounds were identified as the most effective natural inhibitors of SARS-CoV-2 RdRp. These compounds are kaempferol 3-galactoside, kaempferol 3-O-β-D-glucopyranoside, mangiferin methyl ether, luteolin 7-O-β-D-glucopyranoside, quercetin-O-β-D-3-glucopyranoside, 1-methoxy-3-indolylmethyl glucosinolate, naringenin, and asphodelin A 4'-O-β-D-glucopyranoside.
Conclusion: The results of this study provide valuable information for the development of natural product-based drugs against COVID-19. However, the elected compounds should be further studied in vitro and in vivo to confirm their efficacy in treating COVID-19.
期刊介绍:
Antiviral Therapy (an official publication of the International Society of Antiviral Research) is an international, peer-reviewed journal devoted to publishing articles on the clinical development and use of antiviral agents and vaccines, and the treatment of all viral diseases. Antiviral Therapy is one of the leading journals in virology and infectious diseases.
The journal is comprehensive, and publishes articles concerning all clinical aspects of antiviral therapy. It features editorials, original research papers, specially commissioned review articles, letters and book reviews. The journal is aimed at physicians and specialists interested in clinical and basic research.