PARAMETER OPTIMIZATION AND VIRTUAL SCREENING INDONESIAN HERBAL DATABASE AS HUMAN IMMUNODEFICIENCY VIRUS -1 INTEGRASE INHIBITOR USING AUTODOCK AND VINA

Arry Yanuar,Widya Dwi Aryati,Rezi Riadhi Syahdi

doi:10.22159/ijap.2017.v9s1.51_57

Arry Yanuar, Widya Dwi Aryati + Show 1 more

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https://doi.org/10.22159/ijap.2017.v9s1.51_57

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Abstract

Objective: Human immunodeficiency virus (HIV-1) is a virus that causes acquired immunodeficiency syndrome, a disease considered to be one of themost dangerous because of its high mortality, morbidity, and infectivity. The emergence of mutant HIV strains has led treatment to target proteaseas reverse transcriptase and integrase enzyme become less effective. This study aims to provide knowledge about the potential of HIV-1 integraseinhibitors for use as guiding compounds in the development of new anti-HIV drugs.Methods: This study used AutoDock and AutoDock Vina for virtual screening of the Indonesian herbal database for inhibitors of HIV-1 integrase andis validated using a database of the directory of useful decoys. Optimization was accomplished by selecting the grid size, the number of calculations,and the addition of two water molecules and a magnesium atom as cofactor.Results: This study determined that the best grid box size is 21.1725×21.1725×21.1725 in unit space size (1 unit space equals to macromolecules 1Ǻ),using AutoDock Vina with EF and AUC values, 3.93 and 0.693, respectively. Three important water molecules have meaning in molecular dockingaround the binding pocket.Conclusions: This study obtained the top ten ranked compounds using AutoDock Vina. The compounds include: Casuarinin; Myricetin-3-O-(2’’,6’’-di-O-α-rhamnosyl)-β-glucoside; 5,7,2’,4’-tetrahydroxy-6,3’-diprenylisoflavone 5-O-(4’’-rhamnosylrhamnoside); myricetin 3-robinobioside; cyanidin3-[6-(6-ferulylglucosyl)-2-xylosylgalactoside]; mesuein, cyanidin 7-(3-glucosyl-6-malonylglucoside)-4’-glucoside; kaempferol 3-[glucosyl-(1→3)-rhamnosyl-(1→6)-galactoside]; 3-O-galloylepicatechin-(4-β→8)-epicatechin-3-O-gallate; and quercetin 4’-glucuronide.

Highlights

Human immunodeficiency virus (HIV) causes AIDS, which is a syndrome caused by a decrease in the immune system making the body vulnerable to opportunistic infections and neoplastic disease
The emergence of mutant HIV strains has made these drugs ineffective, so we need to find another target in the development of anti-HIV drugs in the integration phase of the HIV DNA life cycle [3]
This study aims to provide knowledge about the potential of HIV-1 integrase inhibitors for use as guiding compounds in the development of new anti-HIV drugs

Summary

Introduction

Human immunodeficiency virus (HIV) causes AIDS (acquired immunodeficiency syndrome), which is a syndrome caused by a decrease in the immune system making the body vulnerable to opportunistic infections and neoplastic disease. HIV decreases the body’s ability handle infections that can normally be resisted by the normal immune systems [1]. Based on the Second Quarterly Report of the Ministry of Health in 2013, there were 108,600 people infected with HIV, and 43,667 of them had reached the AIDS stage in 348 of 497 districts and cities throughout Indonesia, affecting 70% of Indonesia [2]. The active component in the regimens of antiretroviral treatment, highly active antiretroviral therapy, is compounds that target reserve transcriptase and protease, which play a vital role in the HIV life cycle. The emergence of mutant HIV strains has made these drugs ineffective, so we need to find another target in the development of anti-HIV drugs in the integration phase of the HIV DNA life cycle [3]

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