Predicting Antibody Neutralization Efficacy in Hypermutated Epitopes Using Monte Carlo Simulations
POLYMERS
Authors: Amengual-Rigo, Pep; Carrillo, Jorge; Blanco, Julia; Guallar, Victor
Abstract
Human Immunodeficiency Virus 1 (HIV-1) evades adaptive immunity by means of its extremely high mutation rate, which allows the HIV envelope glycoprotein to continuously escape from the action of antibodies. However, some broadly neutralizing antibodies (bNAbs) targeting specific viral regions show the ability to block the infectivity of a large number of viral variants. The discovery of these antibodies opens new avenues in anti-HIV therapy; however, they are still suboptimal tools as their amplitude of action ranges between 50% and 90% of viral variants. In this context, being able to discriminate between sensitive and resistant strains to an antibody would be of great interest for the design of optimal clinical antibody treatments and to engineer potent bNAbs for clinical use. Here, we describe a hierarchical procedure to predict the antibody neutralization efficacy of multiple viral isolates to three well-known anti-CD4bs bNAbs: VRC01, NIH45-46 and 3BNC117. Our method consists of simulating the three-dimensional binding process between the gp120 and the antibody by using Protein Energy Landscape Exploration (PELE), a Monte Carlo stochastic approach. Our results clearly indicate that the binding profiles of sensitive and resistant strains to a bNAb behave differently, showing the latter's weaker binding profiles, that can be exploited for predicting antibody neutralization efficacy in hypermutated HIV-1 strains.
Small double-stranded RNA with anti-HIV activity abundantly produced by Bacillus subtilis MTCC5480 isolated from fermented soybean
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Authors: Imrat; Labala, Rajendra Kumar; Velhal, Shilpa; Bhagat, Sharad; Patel, Vainav; Jeyaram, Kumaraswamy
Abstract
Anti-viral RNA therapy is on high demand nowadays due to the emergence of several new viral infections. The small non-coding regulatory RNAs (dsRNA) from the microbial sources are not yet explored for anti-viral activity. In this study, we assessed the anti-HIV activity of the small dsRNA produced by 12 different microbial species isolated from naturally fermented foods of North-East India. For this, we selectively extracted the dsRNA from the microbial culture, confirmed its double-stranded nature by immunoblotting, and deep sequenced the cDNA library using Illumina platform. Further, we used conventional algorithms to predict the potential targets of the dsRNA sequences within the 3'-UTR region of HIV-1. A small dsRNA fragment with 34 bases in size with a sequence of 3'-UUGGUACACGAGAUCCUUCGACUCGAUGAAGGGC-5' produced abundantly (9.17% of the total dsRNA fraction) by Bacillus subtilis MTCC5480 showed a much higher base complementarity values than previously reported miRNAs analysed against HIV-1. We separated the dsRNA fraction and validated the anti-HIV activity against human peripheral blood mononuclear cells (PBMC) infected with JRCSF strain of HIV-1 virus and the EC50 value ranges from 0.2-03 mu M. This small dsRNA abundantly produced by B. subtilis could be studied further for its application as an anti-viral therapeutic agent. (C) 2018 Elsevier B.V. All rights reserved.