Target specificity of selective bioactive compounds in blocking α-dystroglycan receptor to suppress Lassa virus infection:an in silico approach
Adittya Arefin1
Tanzila Ismail Ema2
Tamnia Islam1
Saddam Hossen3
Tariqul Islam4
Salauddin Al Azad5
Nasir Uddin Badal6
Aminul Islam7
Partha Biswas7
Nafee Ul Alam3
Enayetul Islam8
Maliha Anjum7
Afsana Masud2
Shaikh Kamran9
Ahsab Rahman10
Parag Kumar Paul11
1.Wolfson Institute for Biomedical Research,Division of Medicine,University College London,London WC1E6AE,UK2.Department of Biochemistry and Microbiology,North South University,Dhaka 1229,Bangladesh3.Faculty of Life Sciences and Medicine,Zhejiang Sci-Tech University,Hangzhou,Zhejiang 310018,China4.Faculty of Pharmacy,International Islamic University Malaysia,Kuantan,Pahang 25200,Malaysia5.School of Biotechnology,Jiangnan University,Wuxi,Jiangsu 214122,China6.Department of Biomedical Technology,Tampere University,Tampere 33014,Finland7.Department of Genetic Engineering and Biotechnology,Jashore University of Science and Technology,Jashore 7408,Bangladesh8.Department of Genetic Engineering and Biotechnology,University of Chittagong,Chittagong 4331,Bangladesh9.Applied Statistics and Data Science,Jahangirnagar University,Dhaka 1342,Bangladesh10.Department of Mathematics and Natural Sciences,Brac University,Dhaka 1212,Bangladesh11.Department of Electrical and Electronic Engineering,United International University,Dhaka 1212,Bangladesh
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 the α-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 the α-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.
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分类号：R966(药理学)
论文发表日期：2021-11-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：15( 459-473 )
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