Dual‐Target Repurposing Against Chikungunya Virus: Molecular Docking and Dynamics Reveal Bictegravir and Oxacillin as Promising Leads
- 1School of Pharmacy BRAC University Dhaka Bangladesh bracu.ac.bd
- 2Department of Chemistry Binghamton University The State University of New York Binghamton New York USA suny.edu
- 3Department of Pharmaceutical Chemistry University of Technology Mara Puncak Alam Malaysia uitm.edu.my
Abstract
Chikungunya virus (CHIKV) remains an important re‐emerging arboviral threat, yet no specific antiviral therapy is currently available. This study used a structure‐based drug‐repurposing approach to identify FDA and internationally approved drugs with potential activity against two therapeutically relevant CHIKV targets: nsP2 protease (essential for nonstructural polyprotein processing) and capsid protein (essential for viral nucleocapsid formation). Molecular docking was performed against both proteins, followed by 100‐ns molecular dynamics (MD) simulations of the two highest ranked compounds for each target to assess complex stability. Against nsP2 protease, bictegravir showed the most favorable docking score (−9.5 kcal/mol), followed by simeprevir (−9.3 kcal/mol) and glecaprevir (−9.2 kcal/mol). Against the capsid protein, trovafloxacin ranked first (−8.8 kcal/mol), followed by oxacillin (−8.7 kcal/mol) and paritaprevir (−8.6 kcal/mol). For context, the reference cysteine protease inhibitor E‐64 and the pocket‐validated ligand ethyl 3‐aminobenzoate (EAB) were docked under the identical protocol, and they scored −6.1 and −6.0 kcal/mol against nsP2 protease and capsid protein, respectively, both weaker than every top‐ranked hit identified in this study. MD simulation showed that the bictegravir–nsP2 complex maintained persistently negative total interaction energy, generally within −50 to −30 kcal/mol, with Rg fluctuating from approximately 20.6 to 21.8 Å and RMSD stabilizing initially at 1.2–1.8 Å before reaching a later plateau of 3.0–3.8 Å. By contrast, the simeprevir–nsP2 complex displayed a less uniform energetic profile. For the capsid target, the oxacillin complex remained comparatively restrained, with Rg largely within 22.4–23.2 Å and RMSD mostly within 1.4–2.0 Å, whereas the trovafloxacin complex showed greater conformational drift, with RMSD rising to nearly 2.8–3.1 Å. These computational findings prioritize bictegravir and oxacillin for further investigation against CHIKV nsP2 protease and capsid protein, respectively. No biological validation was performed; target inhibition and antiviral activity therefore remain unconfirmed and require biochemical and cell‐based evaluation.
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BibTeX
@article{raj2026dualtarget,
title = {{Dual‐Target Repurposing Against Chikungunya Virus: Molecular Docking and Dynamics Reveal Bictegravir and Oxacillin as Promising Leads}},
author = {Asef Raj and Humair Bin Md Omer and Mim Deb Roy and Aisha Siddika and Sabrina Sharmin},
journal = {BioMed Research International},
year = {2026},
month = nov,
doi = {10.1155/bmri/1672620},
url = {https://doi.org/10.1155/bmri/1672620},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dual‐Target Repurposing Against Chikungunya Virus: Molecular Docking and Dynamics Reveal Bictegravir and Oxacillin as Promising Leads
AU - Asef Raj
AU - Humair Bin Md Omer
AU - Mim Deb Roy
AU - Aisha Siddika
AU - Sabrina Sharmin
PY - 2026
DA - 2026/11/04
JO - BioMed Research International
DO - 10.1155/bmri/1672620
UR - https://doi.org/10.1155/bmri/1672620
AB - Chikungunya virus (CHIKV) remains an important re‐emerging arboviral threat, yet no specific antiviral therapy is currently available. This study used a structure‐based drug‐repurposing approach to identify FDA and internationally approved drugs with potential activity against two therapeutically relevant CHIKV targets: nsP2 protease (essential for nonstructural polyprotein processing) and capsid protein (essential for viral nucleocapsid formation). Molecular docking was performed against both proteins, followed by 100‐ns molecular dynamics (MD) simulations of the two highest ranked compounds for each target to assess complex stability. Against nsP2 protease, bictegravir showed the most favorable docking score (−9.5 kcal/mol), followed by simeprevir (−9.3 kcal/mol) and glecaprevir (−9.2 kcal/mol). Against the capsid protein, trovafloxacin ranked first (−8.8 kcal/mol), followed by oxacillin (−8.7 kcal/mol) and paritaprevir (−8.6 kcal/mol). For context, the reference cysteine protease inhibitor E‐64 and the pocket‐validated ligand ethyl 3‐aminobenzoate (EAB) were docked under the identical protocol, and they scored −6.1 and −6.0 kcal/mol against nsP2 protease and capsid protein, respectively, both weaker than every top‐ranked hit identified in this study. MD simulation showed that the bictegravir–nsP2 complex maintained persistently negative total interaction energy, generally within −50 to −30 kcal/mol, with Rg fluctuating from approximately 20.6 to 21.8 Å and RMSD stabilizing initially at 1.2–1.8 Å before reaching a later plateau of 3.0–3.8 Å. By contrast, the simeprevir–nsP2 complex displayed a less uniform energetic profile. For the capsid target, the oxacillin complex remained comparatively restrained, with Rg largely within 22.4–23.2 Å and RMSD mostly within 1.4–2.0 Å, whereas the trovafloxacin complex showed greater conformational drift, with RMSD rising to nearly 2.8–3.1 Å. These computational findings prioritize bictegravir and oxacillin for further investigation against CHIKV nsP2 protease and capsid protein, respectively. No biological validation was performed; target inhibition and antiviral activity therefore remain unconfirmed and require biochemical and cell‐based evaluation.
SN - 2314-6133
SN - 2314-6141
ER -