<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>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.<fig id="j_pjm-2024-020_fig_001" position="float" fig-type="figure">
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/j_pjm-2024-020_fig_001.jpg"></graphic>
</fig></p>
</abstract>

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.

Halogenated Secondary Metabolites from Higher Plants: Potent Drug Candidates for Chikungunya Using <italic>in silico</italic> Approaches

Polish Journal of Microbiology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Halogenated Secondary Metabolites from Higher Plants: Potent Drug Candidates for Chikungunya Using  Approaches

Chikungunya virus (CHIKV) causes a debilitating fever and joint pain, with no specific antiviral treatment available. Halogenated secondary metabolites from...

Energy components	Values (kJ/mol)
van der Waals energy	−238.144 ± 15.134
Electrostatic energy	−17.868 ± 5.685
Polar solvation energy	65.878 ± 10.659
SASA energy	−17.349 ± 1.177
Binding energy	−207.483 ± 15.414

Parameter	Control	Pipoxide chlorohydrin
Backbone RMSD	0.38566 ± 0.04087	0.33465 ± 0.01483
Ligand RMSD		0.6465 ± 0.10423
Complex RMSD		0.33977 ± 0.01469
RMSF	0.15901 ± 0.06542	0.122 ± 0.04224
Radius of gyration	1.98671 ± 0.01127	1.98117 ± 0.01406
SASA	142.80578 ± 3.86427	144.61529 ± 3.2153

Halogenated Secondary Metabolites from Higher Plants: Potent Drug Candidates for Chikungunya Using in silico Approaches

Article Category: Original Paper

Published Online: Jun 20, 2024

Page range: 207 - 215

Received: Feb 21, 2024

Accepted: May 03, 2024

DOI: https://doi.org/10.33073/pjm-2024-020

Keywords
Chikungunya virus, nsP2 cysteine protease, traditional medicine, drug candidates, molecular docking, MD simulation, pipoxide chlorohydrin

© 2024 Sushil Kumar et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) computed energy components.

Average MD simulation parameters.

Halogenated Secondary Metabolites from Higher Plants: Potent Drug Candidates for Chikungunya Using in silico Approaches

Article Category: Original Paper

Published Online: Jun 20, 2024

Page range: 207 - 215

Received: Feb 21, 2024

Accepted: May 03, 2024

DOI: https://doi.org/10.33073/pjm-2024-020

KeywordsChikungunya virus, nsP2 cysteine protease, traditional medicine, drug candidates, molecular docking, MD simulation, pipoxide chlorohydrin

© 2024 Sushil Kumar et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) computed energy components.

Average MD simulation parameters.

Keywords
Chikungunya virus, nsP2 cysteine protease, traditional medicine, drug candidates, molecular docking, MD simulation, pipoxide chlorohydrin