In-Silico Identification of Potential NS2B-NS3 Protease Inhibitors against Zika Virus
In-Silico Identification of Potential NS2B-NS3 Protease Inhibitors against Zika Virus
Nusrat Jahan Lily1*, Kazi Abdus Sobur2, Minhaz Zabin Saif Mim3, Anika Thasin Bithi4, Hamja Hasanat5, Tabassum Mounita5, Foysal Ahammad6,7, Abdus Samad7,8 and Palash Bose2
ABSTRACT
Zika virus transmitted by mosquito, has emerged as a significant public health threat with the potential to cause global pandemics. This study explores natural phytochemicals as potential inhibitors of Zika virus (ZIKV) infection by targeting the essential NS2B-NS3 protease complex, which plays a crucial role in viral replication. A virtual screening library of 52 natural compounds was prepared, followed by pharmacokinetic (ADME) and toxicity assessments to identify two promising candidates. These selected compounds were further analyzed through molecular docking and extensive 200-nanosecond molecular dynamics simulations to evaluate binding affinity, stability, and interaction with the ZIKV protease structure (PDB ID: 5LC0). Among the tested ligands, PubChem CID: 56649692 showed the most favorable binding affinity at -5.321 kcal/mol, surpassing other compounds, including the control ligand. Molecular dynamics simulation confirmed that CID: 56649692 maintained stability within the acceptable range, as reflected in root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) values. The stability was further supported by the formation of multiple hydrogen bonds and hydrophobic interactions with key residues (LYS1119, ASP1120, and LYS1073) in the protease’s active site, indicating strong and stable ligand-protein interactions. CID: 56649692 demonstrates significant potential as a lead compound for ZIKV inhibition based on its high binding affinity, molecular stability, and favorable ADME and toxicity profiles. Targeting the NS2B-NS3 protease complex represents a promising strategy to disrupt ZIKV replication, supporting CID: 56649692 as a viable candidate for further investigation. Future in vitro and in vivo studies are recommended to validate these in silico findings and assess the therapeutic efficacy of CID: 56649692 under physiological conditions.
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