Halogenated Secondary Metabolites from Higher Plants: Potent Drug Candidates for Chikungunya Using in silico Approaches.
Sushil KumarNidhi JoshiGourav ChoudhirSakshi SharmaAbhay TiwariSulaiman Ali AlharbiSaleh AlfarrajMohammad Javed AnsariPublished in: Polish journal of microbiology (2024)
Chikungunya virus (CHIKV) causes a debilitating fever and joint pain, with no specific antiviral treatment available. Halogenated secondary metabolites from plants are a promising new class of drug candidates against chikungunya, with unique properties that make them effective against the virus. Plants produce these compounds to defend themselves against pests and pathogens, and they are effective against a wide range of viruses, including chikungunya. This study investigated the interactions of halogenated secondary metabolites with nsP2pro, a therapeutic target for CHIKV. A library of sixty-six halogenated plant metabolites screened previously for ADME properties was used. Metabolites without violation of Lipinski's rule were docked with nsP2pro using AutoDock Vina. To find the stability of the pipoxide chlorohydrin-nsP2pro complex, the GROMACS suite was used for MD simulation. The binding free energy of the ligand-protein complex was computed using MMPBSA. Molecular docking studies revealed that halogenated metabolites interact with nsP2pro, suggesting they are possible inhibitors. Pipoxide chlorohydrin showed the greatest affinity to the target. This was further confirmed by the MD simulations, surface accessible area, and MMPBSA studies. Pipoxide chlorohydrin, a halogenated metabolite, was the most potent against nsP2pro in the survey.
Keyphrases
- molecular docking
- ms ms
- anti inflammatory
- zika virus
- aedes aegypti
- dengue virus
- molecular dynamics
- chronic pain
- neuropathic pain
- emergency department
- high resolution
- cross sectional
- magnetic resonance
- small molecule
- transcription factor
- case control
- single cell
- adverse drug
- protein protein
- multidrug resistant
- contrast enhanced
- cell wall
- disease virus