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A Theoretical Model to Study the Interaction of Erythro‐Noscapines with nsP3 protease of Chikungunya Virus
Author(s) -
Kumar Durgesh,
Singh Prashant,
Jayaraj Abhilash,
Kumar Vinod,
Kumari Kamlesh,
Patel Rajan
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803360
Subject(s) - protease , chikungunya , chemistry , docking (animal) , viral replication , virus , binding energy , molecular mechanics , virology , stereochemistry , computational chemistry , molecular dynamics , biology , biochemistry , physics , enzyme , quantum mechanics , veterinary medicine , medicine
Abstract For the better management and control of the viral replication, it is essential to discover a potential molecule to combat Chikungunya virus (CHIKV). The work aims to find a potential antiviral molecule via its interactions with the non‐structural protease (nsP3) of CHIKV. It plays a crucial role in intracellular replication. The best molecular interaction is based on the minimum total binding energy of hydrogen bonding, electrostatic interaction and van der Waals forces. It was found that Erythro‐noscapines showed good binding affinity with nsP3 protease of CHIKV (PDB ID: 3GPO) and minimum total binding energy (‐149.964 kcal/mol) to form a more stable complex i. e. 109‐nsP3 protease of CHIKV. Erythro‐noscapines (109, one of the derivatives of erythro‐noscapine) showed better interaction than the reported molecules by different reseach groups via docking. The parameters for bioactivity score and Lipinski “Rule of Five” were calculated to estimate the pharmacokinetic properties of antiviral Erythro‐noscapines and compared to others. 109 can be considered as a good candidate for antiviral replication against nsP3 protease of CHIKV. Molecular dynamics simulations on nsP3 protease of CHIKV with or without 109 was performed and studied. Further, binding free energies of potential noscapine‐nsP3 protease of CHIKV based on Molecular Mechanics‐Generalized Born Suface Area (MM‐GBSA) was calculated. Further, toxicity of top 10 noscapines and reported molecules by different research groups was determined and then, density functional theory was applied to understand the singlet and triplet states of the 109.