TY - JOUR
T1 - Target specificity of selective bioactive compounds in blocking α-dystroglycan receptor to suppress Lassa virus infection
T2 - an in silico approach
AU - Arefin, Adittya
AU - Ema, Tanzila Ismail
AU - Islam, Tamnia
AU - Hossen, Md Saddam
AU - Islam, Tariqul
AU - Azad, Salauddin Al
AU - Badal, Md Nasir Uddin
AU - Islam, Md Aminul
AU - Biswas, Partha
AU - Alam, Nafee Ul
AU - Islam, Enayetul
AU - Anjum, Maliha
AU - Masud, Afsana
AU - Kamran, Md Shaikh
AU - Rahman, Ahsab
AU - Paul, Parag Kumar
N1 - Funding Information:
The authors must extend their respect and satisfaction to RPG Organization (Govt. Registration ID: 05-060-06021) for ensuring all technical supports in cordial collaboration as part of excellent organizational technology transfer and faculty exchange under the Project 'Category F3 (ID. #08-2021/22)'.
Publisher Copyright:
© 2021. by the Journal of Biomedical Research.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Bioactive compounds
KW - Lasv infection
KW - Molecular docking
KW - Molecular dynamic simulations
KW - Target specificity
KW - Α-dystroglycan receptor
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U2 - 10.7555/JBR.35.20210111
DO - 10.7555/JBR.35.20210111
M3 - Article
AN - SCOPUS:85121833705
VL - 35
SP - 459
EP - 473
JO - Journal of Biomedical Research
JF - Journal of Biomedical Research
SN - 1674-8301
IS - 6
ER -