Parameter Optimization and Virtual Screening Indonesian Herbal Database as Human Immunodeficiency Virus -1 Integrase Inhibitor Using Autodock and Vina

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.

Investigating the Frequency of Occupational Exposure in Dentistry Students of Ahvaz Jundishapur University of Medical Sciences in Southwest of Iran

“…Health and medical employees, especially physicians and dentists, are at two major risks regarding the infectious diseases. First, they are at a higher risk of infectious agents than other people, and they are considered as potential vector for transmission of infectious agents to their patients [10]. Among health personnel, dentists and their patients are always at a high risk of infections transmitted through blood due to blood-borne infections and other body fluids [11].…”

Pharmacophore and Molecular Docking-Based Virtual Screening of B-Cell Lymphoma 2 (BCL 2) Inhibitor from Zinc Natural Database as Anti-Small Cell Lung Cancer

“…Virtual screening (VS) is a computational filter to reduce the size of a chemical library that will be identified experimentally and offers opportunities to quickly reduce the time and effort associated with identification 7 . VS is described as the use of high-performance computational calculations in analyzing a database of many chemical compounds in order to identify the probability of drug candidates 22 . There are two fundamental approaches to virtual screening: the ligand-based approach and the receptor-based approach.…”

A Review on the Antiparasitic Drug Ivermectin for Various Viral Infections and Possibilities of Using It for Novel Severe Acute Respiratory Syndrome Coronavirus 2: New Hope to Treat Coronavirus Disease-2019

“…The study reveals that IVM at a dose of 5 µM inhibits the replication of SARS-CoV-2 in vitro with an IC 50 of 2.2-2.8 µM, which is similar to the efficacy of IVM in dengue virus (IC 50 : 2.2µM for DENVI). Further, a single addition of IVM 2-h post-infection with SARS-CoV-2 was able to effect ≈5000 fold reduction in viral RNA at 48 h. At 24 th h, there was a 93% reduction in viral RNA and a 99.98% reduction at 48 th h. In an observational registrybased study [7] from 169 hospitals with 1970 COVID-19 patient's with lung injury requiring mechanical ventilation across Asia, Europe, Africa, North, and South America, the IVM, 150 mcg/kg treatment group (n=52) has lesser mortality rate, length of stay in intensive care unit and hospital compared to that of n=1918 conventionally treated patients (mortality rate=7.7% vs. 18.6%; hospital length of stay=10.9±6.1 days vs. 15.7±8.1 days, and intensive care unit length of stay=6.0±3.9 days vs. 8.2±6.2 days for IVM, and conventional treatment group resp, all at p<0.001 resp). This study was first of its kind for evaluating the significance of IVM in the treatment of COVID-19 in in vivo.…”

“…Ivermectin (IVM), one such drug which is originally used to treat parasitic infections, has recently been found to inhibit the replication of novel SARS-CoV-2 within 48 h in laboratory settings [6]. The very recent observational registry-based study from 169 hospitals across different countries revealed that IVM treated group of COVID-19 critically ill patients requiring mechanical ventilation has lower mortality and healthcare resource used [7]. IVM is an Food and Drug Administration (FDA)-approved anti-parasitic drug that has also been shown to be effective in vitro against a broad range of viruses, including human immunodeficiency virus (HIV), dengue, and influenza [8,9].…”