Target specificity of selective bioactive compounds in blocking α-dystroglycan receptor to suppress Lassa virus infection: an in silico approach  

作　　者：Adittya Arefin Tanzila Ismail Ema Tamnia Islam MdSaddam Hossen Tariqul Islam Salauddin Al Azad MdNasir Uddin Badal MdAminul Islam Partha Biswas Nafee Ul Alam Enayetul Islam Maliha Anjum Afsana Masud MdShaikh Kamran Ahsab Rahman Parag Kumar Paul 

机构地区：[1]Wolfson Institute for Biomedical Research,Division of Medicine,University College London,London WC1E6AE,UK [2]Department of Biochemistry and Microbiology,North South University,Dhaka 1229,Bangladesh [3]Faculty of Life Sciences and Medicine,Zhejiang Sci-Tech University,Hangzhou,Zhejiang 310018,China [4]Faculty of Pharmacy,International Islamic University Malaysia,Kuantan,Pahang 25200,Malaysia [5]School of Biotechnology,Jiangnan University,Wuxi,Jiangsu 214122,China [6]Department of Biomedical Technology,Tampere University,Tampere 33014,Finland [7]Department of Genetic Engineering and Biotechnology,Jashore University of Science and Technology,Jashore 7408,Bangladesh [8]Department of Genetic Engineering and Biotechnology,University of Chittagong,Chittagong 4331,Bangladesh [9]Applied Statistics and Data Science,Jahangirnagar University,Dhaka 1342,Bangladesh [10]Department of Mathematics and Natural Sciences,Brac University,Dhaka 1212,Bangladesh [11]Department of Electrical and Electronic Engineering,United International University,Dhaka 1212,Bangladesh.

出　　处：《The Journal of Biomedical Research》2021年第6期459-473,共15页生物医学研究杂志（英文版）

摘　　要：Lassa hemorrhagic fever,caused by Lassa mammarenavirus(LASV)infection,accumulates up to 5000 deaths every year.Currently,there is no vaccine available to combat this disease.In this study,a library of 200 bioactive compounds was virtually screened to study their drug-likeness with the capacity to block theα-dystroglycan(α-DG)receptor and prevent LASV influx.Following rigorous absorption,distribution,metabolism,and excretion(ADME)and quantitative structure-activity relationship(QSAR)profiling,molecular docking was conducted with the top ligands against theα-DG receptor.The compounds chrysin,reticuline,and 3-caffeoylshikimic acid emerged as the top three ligands in terms of binding affinity.Post-docking analysis revealed that interactions with Arg76,Asn224,Ser259,and Lys302 amino acid residues of the receptor protein were important for the optimum binding affinity of ligands.Molecular dynamics simulation was performed comprehensively to study the stability of the protein-ligand complexes.In-depth assessment of root-mean-square deviation(RMSD),root mean square fluctuation(RMSF),polar surface area(PSA),B-Factor,radius of gyration(Rg),solvent accessible surface area(SASA),and molecular surface area(MolSA)values of the protein-ligand complexes affirmed that the candidates with the best binding affinity formed the most stable protein-ligand complexes.To authenticate the potentialities of the ligands as target-specific drugs,an in vivo study is underway in real time as the continuation of the research.

关 键 词：LASV infection α-dystroglycan receptor bioactive compounds target specificity molecular docking molecular dynamic simulations 

分 类 号：R966[医药卫生—药理学]