First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients

Abstract Background NS5A and NS5B proteins of hepatitis C virus (HCV) are the main targets of compounds that directly inhibit HCV infections. However, the emergence of resistance-associated substitutions (RASs) may cause substantial reductions in susceptibility to inhibitors. Methods Viral load and...

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Autores principales:	Zahra Hasanshahi, Ava Hashempour, Farzane Ghasabi, Javad Moayedi, Zahra Musavi, Behzad Dehghani, Heidar Sharafi, Hassan Joulaei
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	HCV NS5A NS5B Drug-resistance Bioinformatics Iran Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/26e1999e836e4135ad9b6588156afa79
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spelling	oai:doaj.org-article:26e1999e836e4135ad9b6588156afa792021-11-28T12:15:07ZFirst report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients10.1186/s12876-021-01988-y1471-230Xhttps://doaj.org/article/26e1999e836e4135ad9b6588156afa792021-11-01T00:00:00Zhttps://doi.org/10.1186/s12876-021-01988-yhttps://doaj.org/toc/1471-230XAbstract Background NS5A and NS5B proteins of hepatitis C virus (HCV) are the main targets of compounds that directly inhibit HCV infections. However, the emergence of resistance-associated substitutions (RASs) may cause substantial reductions in susceptibility to inhibitors. Methods Viral load and genotyping were determined in eighty-seven naïve HCV-infected patients, and the amplified NS5A and NS5B regions were sequenced by Sanger sequencing. In addition, physicochemical properties, structural features, immune epitopes, and inhibitors-protein interactions of sequences were analyzed using several bioinformatics tools. Results Several amino acid residue changes were found in NS5A and NS5B proteins; however, we did not find any mutations related to resistance to the treatment in NS5B. Different phosphorylation and few glycosylation sites were assessed. Disulfide bonds were identified in both proteins that had a significant effect on the function and structure of HCV proteins. Applying reliable software to predict B-cell epitopes, 3 and 5 regions were found for NS5A and NS5B, respectively, representing a considerable potential to induce the humoral immune system. Docking analysis determined amino acids involved in the interaction of inhibitors and mentioned proteins may not decrease the drug efficiency. Conclusions Strong interactions between inhibitors, NS5A and NS5B proteins and the lack of efficient drug resistance mutations in the analyzed sequences may confirm the remarkable ability of NS5A and NS5B inhibitors to control HCV infection amongst Iranian patients. The results of bioinformatics analysis could unveil all features of both proteins, which can be beneficial for further investigations on HCV drug resistance and designing novel vaccines.Zahra HasanshahiAva HashempourFarzane GhasabiJavad MoayediZahra MusaviBehzad DehghaniHeidar SharafiHassan JoulaeiBMCarticleHCVNS5ANS5BDrug-resistanceBioinformaticsIranDiseases of the digestive system. GastroenterologyRC799-869ENBMC Gastroenterology, Vol 21, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HCV NS5A NS5B Drug-resistance Bioinformatics Iran Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	HCV NS5A NS5B Drug-resistance Bioinformatics Iran Diseases of the digestive system. Gastroenterology RC799-869 Zahra Hasanshahi Ava Hashempour Farzane Ghasabi Javad Moayedi Zahra Musavi Behzad Dehghani Heidar Sharafi Hassan Joulaei First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients
description	Abstract Background NS5A and NS5B proteins of hepatitis C virus (HCV) are the main targets of compounds that directly inhibit HCV infections. However, the emergence of resistance-associated substitutions (RASs) may cause substantial reductions in susceptibility to inhibitors. Methods Viral load and genotyping were determined in eighty-seven naïve HCV-infected patients, and the amplified NS5A and NS5B regions were sequenced by Sanger sequencing. In addition, physicochemical properties, structural features, immune epitopes, and inhibitors-protein interactions of sequences were analyzed using several bioinformatics tools. Results Several amino acid residue changes were found in NS5A and NS5B proteins; however, we did not find any mutations related to resistance to the treatment in NS5B. Different phosphorylation and few glycosylation sites were assessed. Disulfide bonds were identified in both proteins that had a significant effect on the function and structure of HCV proteins. Applying reliable software to predict B-cell epitopes, 3 and 5 regions were found for NS5A and NS5B, respectively, representing a considerable potential to induce the humoral immune system. Docking analysis determined amino acids involved in the interaction of inhibitors and mentioned proteins may not decrease the drug efficiency. Conclusions Strong interactions between inhibitors, NS5A and NS5B proteins and the lack of efficient drug resistance mutations in the analyzed sequences may confirm the remarkable ability of NS5A and NS5B inhibitors to control HCV infection amongst Iranian patients. The results of bioinformatics analysis could unveil all features of both proteins, which can be beneficial for further investigations on HCV drug resistance and designing novel vaccines.
format	article
author	Zahra Hasanshahi Ava Hashempour Farzane Ghasabi Javad Moayedi Zahra Musavi Behzad Dehghani Heidar Sharafi Hassan Joulaei
author_facet	Zahra Hasanshahi Ava Hashempour Farzane Ghasabi Javad Moayedi Zahra Musavi Behzad Dehghani Heidar Sharafi Hassan Joulaei
author_sort	Zahra Hasanshahi
title	First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients
title_short	First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients
title_full	First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients
title_fullStr	First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients
title_full_unstemmed	First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients
title_sort	first report on molecular docking analysis and drug resistance substitutions to approved hcv ns5a and ns5b inhibitors amongst iranian patients
publisher	BMC
publishDate	2021
url	https://doaj.org/article/26e1999e836e4135ad9b6588156afa79
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First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients

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