Research Article

Natural Metabolites from Clinacanthus nutans as Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations

Volume: 2026 Number: 2 September 10, 2026

Natural Metabolites from Clinacanthus nutans as Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations

Abstract

Structure-based drug design against SARS-CoV-2 main protease (Mpro) was enabled by the availability of its crystal structure (PDB ID: 6LU7). In this study, metabolites from Clinacanthus nutans were computationally evaluated as potential Mpro inhibitors using validated molecular docking and molecular dynamics (MD) approaches. Native ligand re-docking produced an RMSD of 1.329 Å, confirming the reliability of the docking setup. Among the tested compounds, vitexin demonstrated a favorable binding affinity in docking analysis, indicating its potential for interaction within the active site of Mpro. However, further evaluation using 100 ns MD simulations and MM/PBSA free energy calculations revealed that, although the vitexin–Mpro complex remained relatively stable, the native ligand exhibited superior thermodynamic stability and binding free energy. Overall, vitexin shows promising binding characteristics as a natural compound targeting Mpro, but it does not surpass the native ligand in terms of overall binding stability. These findings suggest that vitexin may serve as a potential lead compound, warranting further optimization and experimental validation.

Keywords

References

  1. 1. WHO. Coronavirus disease (COVID-2019) situation reports. World Heal Organ. 2020;
  2. 2. Rut W, Groborz K, Zhang L, Sun X, Zmudzinski M, Pawlik B, et al. SARS-CoV-2 Mpro inhibitors and activity-based probes for patient-sample imaging. Nat Chem Biol. 2021 Feb 22;17(2):222–8. Available from: .
  3. 3. Reiner Ž, Hatamipour M, Banach M, Pirro M, Al-Rasadi K, Jamialahmadi T, et al. Statins and the COVID-19 main protease: In silico evidence on direct interaction. Arch Med Sci. 2020;16(3):490–6. Available from: .
  4. 4. Enmozhi SK, Raja K, Sebastine I, Joseph J. Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: An in silico approach. J Biomol Struct Dyn. 2020 May 5;39(9):3092–8. Available from: .
  5. 5. Sinha SK, Shakya A, Prasad SK, Singh S, Gurav NS, Prasad RS, et al. An in-silico evaluation of different Saikosaponins for their potency against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets. J Biomol Struct Dyn. 2020 May 13;39(9):3244–55. Available from: .
  6. 6. Ogidigo JO, Iwuchukwu EA, Ibeji CU, Okpalefe O, Soliman MES. Natural phyto, compounds as possible noncovalent inhibitors against SARS-CoV2 protease: Computational approach. J Biomol Struct Dyn. 2022 Mar 24;40(5):2284–301. Available from: .
  7. 7. Ramadhan DSF, Siharis F, Abdurrahman S, Isrul M, Fakih TM. In silico analysis of marine natural product from sponge (Clathria Sp.) for their activity as inhibitor of SARS-CoV-2 main protease. J Biomol Struct Dyn. 2022 Dec 12;40(22):11526–32. Available from: .
  8. 8. Zulkipli IN, Rajabalaya R, Idris A, Sulaiman NA, David SR. Clinacanthus nutans : A review on ethnomedicinal uses, chemical constituents and pharmacological properties. Pharm Biol. 2017 Jan 15;55(1):1093–113. Available from: .

Details

Primary Language

English

Subjects

Natural Products and Bioactive Compounds, Biomolecular Modelling and Design

Journal Section

Research Article

Publication Date

September 10, 2026

Submission Date

November 9, 2025

Acceptance Date

August 8, 2026

Published in Issue

Year 2026 Volume: 2026 Number: 2

APA
Djasang, S., & Artati, A. (2026). Natural Metabolites from Clinacanthus nutans as Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations. Journal of the Turkish Chemical Society Section A: Chemistry, 2026(2), 1-9. https://doi.org/10.18596/jotcsa.1820541
AMA
1.Djasang S, Artati A. Natural Metabolites from Clinacanthus nutans as Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations. JOTCSA. 2026;2026(2):1-9. doi:10.18596/jotcsa.1820541
Chicago
Djasang, Syahida, and Artati Artati. 2026. “Natural Metabolites from Clinacanthus Nutans As Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations”. Journal of the Turkish Chemical Society Section A: Chemistry 2026 (2): 1-9. https://doi.org/10.18596/jotcsa.1820541.
EndNote
Djasang S, Artati A (September 1, 2026) Natural Metabolites from Clinacanthus nutans as Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations. Journal of the Turkish Chemical Society Section A: Chemistry 2026 2 1–9.
IEEE
[1]S. Djasang and A. Artati, “Natural Metabolites from Clinacanthus nutans as Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations”, JOTCSA, vol. 2026, no. 2, pp. 1–9, Sept. 2026, doi: 10.18596/jotcsa.1820541.
ISNAD
Djasang, Syahida - Artati, Artati. “Natural Metabolites from Clinacanthus Nutans As Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations”. Journal of the Turkish Chemical Society Section A: Chemistry 2026/2 (September 1, 2026): 1-9. https://doi.org/10.18596/jotcsa.1820541.
JAMA
1.Djasang S, Artati A. Natural Metabolites from Clinacanthus nutans as Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations. JOTCSA. 2026;2026:1–9.
MLA
Djasang, Syahida, and Artati Artati. “Natural Metabolites from Clinacanthus Nutans As Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations”. Journal of the Turkish Chemical Society Section A: Chemistry, vol. 2026, no. 2, Sept. 2026, pp. 1-9, doi:10.18596/jotcsa.1820541.
Vancouver
1.Syahida Djasang, Artati Artati. Natural Metabolites from Clinacanthus nutans as Promising SARS-CoV-2 Main Protease Inhibitors: Insights from Molecular Docking and Dynamics Simulations. JOTCSA. 2026 Sep. 1;2026(2):1-9. doi:10.18596/jotcsa.1820541