Modeling of human CCR5 as Target for HIV-I and Virtual Screening with Marine Therapeutic compounds

Selvaraj Manikandan,B K Malik

doi:10.6026/97320630003089

Abstract

Marine derivatives are of great pharmaceutical interest as inhibitory compound and search of bioactive compounds from Marine organism which is relatively new to medicinal chemistry. Our main aim in the study is to screen possible inhibitors against CCR5 which acts as co-receptor M-tropic HIV-1, through virtual screening of 122 Marine derived compounds from various organisms known to have biological activity. Homology Model of CCR5 was constructed using MODELLER and the Model was energy minimized and validated using PROCHECK to obtain a stable structure, which was further used for virtual screening of Marine derived compounds through molecular Docking studies using GOLD. The Docked complexes were validated and Enumerated based on the GOLD Scoring function to pick out the best Marine inhibitor based on GOLD score. Thus from the entire 122 Marine compounds which were Docked, we got best 4 of them with optimal GOLD Score. (LAMIVUDINE: 45.0218, BATZELLINE-D: 44.3852.ACYCLOVIR: 43.1362 and THIIOACETAMIDE: 42.7412) Further the Complexes were analyzed through LIGPLOT for their interaction for the 4 best docked Marine compounds. Thus from the Complex scoring and binding ability its deciphered that these Marine compounds could be promising inhibitors for M-tropic HIV-1 using CCR5 as Drug target yet pharmacological studies have to confirm it.

Highlights

In AIDS therapy, there are currently a number of compounds available for multiple targets approved by the FDA and in clinical trials, e.g. protease inhibitors, reverse transcriptase inhibitors (NRTI, NNRTI) and CCR5, CCR4, fusion inhibitors, among others [1,2,3,4]
Our main aim in the study is to screen possible inhibitors against CCR5 which acts as co-receptor M-tropic HIV-1, through virtual screening of 122 Marine derived compounds from various organisms known to have biological activity
Our PDB BLAST Hit for CCR5 target sequence gave a best hit of Rhodopsin crystal structure (PDB: 1F88) .The Initial Model generated using MODELLER

Summary

Introduction

In AIDS therapy, there are currently a number of compounds available for multiple targets approved by the FDA and in clinical trials, e.g. protease inhibitors, reverse transcriptase inhibitors (NRTI, NNRTI) and CCR5, CCR4, fusion inhibitors, among others [1,2,3,4]. Modeling of human CCR5 as target for HIV-I and virtual screening with marine therapeutic compounds

Results

Conclusion