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41709

In Silico DISCOVERY OF NOVEL HEPATITIS C VIRUS P7-TRANSACTIVATED PROTEIN1INHIBITOR BY USING STRUCTURE-BASED VIRTUAL SCREENING

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Last updated: 04 Jan 2025

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Abstract

Hepatitis C Virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at a risk of developing significant morbidity and mortality. Till date there is no effective drug for the treatment or vaccine to prevent this infection. The present study aims in discovering novel inhibitors which target an allosteric binding site of P7-transactivated Protein1 of HCV. Virtual screening uses computer-based methods to discover new ligands on the basis of biological structures.  A structure based virtual screening of Zinc database by computational docking and the post docking analysis of energy calculations and interactions followed by ADMET studies were conducted. The approach adopted was receptor-based.  Docking screens, guided with contact pharmacophores and neural-network activity prediction models on all allosteric binding sites and MD simulations, constituted our analysis workflow for identification of potential hits. Steps included: 1) Using two phases docking screen with moe and Glide Xp programs,  2) Ranking based on scores, and important H interactions. From the final hits, we selected best 10 compounds for further anti-HCV activity and cellular cytotoxicity assay. All 10 compounds have more potential to be considered as lead compoundsto inhibit ion channel activity of p7 with docking score and binding energy (E_score) values ranging from -16.5087 to -15.8089 and all these compounds displayed no cellular cytotoxicity. Finally, 10 hit compounds of different scaffolds having interactions with important active site residues were predicted as lead candidates. These candidates having unique scaffolds have a strong likelihood to act as further starting points in the optimization and development of novel and potent p7 ion channel inhibitors.    

DOI

10.21608/jpd.2017.41709

Keywords

In SilicoDiscovery, Novel Hepatitis C Virus P7-Transactivated Protein1inhibitor, Using Structure-Based, Virtual Screening

Authors

First Name

Mahmoud

Last Name

El Hefnawi

MiddleName

-

Affiliation

Informatics and Systems Department, Division of Engineering Research Sciences, the National Research Centre, Egypt :mahef@aucegypt.edu

Email

-

City

Sadat city

Orcid

-

First Name

Mohamed

Last Name

Hasan

MiddleName

-

Affiliation

Bioinformatics Department, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Egypt

Email

-

City

Sadat city

Orcid

-

First Name

Amal

Last Name

Mahmoud

MiddleName

-

Affiliation

Bioinformatics Department, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Egypt

Email

-

City

Sadat city

Orcid

-

First Name

El-Sayed

Last Name

El-Absawy

MiddleName

-

Affiliation

Bioinformatics Department, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Egypt

Email

-

City

Sadat city

Orcid

-

First Name

Alaa

Last Name

Hemeida

MiddleName

-

Affiliation

Bioinformatics Department, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Egypt

Email

-

City

Sadat city

Orcid

-

First Name

Yahia

Last Name

Khidr

MiddleName

-

Affiliation

Plant Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Egypt

Email

-

City

Sadat city

Orcid

-

Volume

22

Article Issue

1

Related Issue

6555

Issue Date

2017-01-01

Receive Date

2016-10-15

Publish Date

2017-01-01

Page Start

103

Page End

119

Print ISSN

1110-2543

Online ISSN

2682-3322

Article File

JPD_Volume 22_Issue 1_Pages 103-119.pdf

PDF . 560.9kB

Link

https://jpd.journals.ekb.eg/article_41709.html

Detail API

https://jpd.journals.ekb.eg/service?article_code=41709

Order

7

Type

Original Article

Type Code

867

Publication Type

Journal

Publication Title

Journal of Productivity and Development

Publication Link

https://jpd.journals.ekb.eg/

MainTitle

In Silico DISCOVERY OF NOVEL HEPATITIS C VIRUS P7-TRANSACTIVATED PROTEIN1INHIBITOR BY USING STRUCTURE-BASED VIRTUAL SCREENING

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Type

Article

Created At

22 Jan 2023