AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.8293
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ORIGINAL RESEARCH ARTICLE

Molecular binding of 11q to NS2B–NS3 proteases of dengue and West Nile viruses

Ramprakash Yadav1 ,  Nihar Ranjan Jena1*
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1 Discipline of Natural Sciences, Indian Institute of Information Technology, Design and Manufacturing, Jabalpur, Madhya Pradesh, India
GPD, 8293 https://doi.org/10.36922/gpd.8293
Received: 30 December 2024 | Revised: 14 May 2025 | Accepted: 14 May 2025 | Published online: 4 June 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Dengue virus (DENV) and West Nile virus (WNV) are mosquito-borne pathogens that cause severe health burdens globally. Despite their impact, no clinically approved antiviral therapies are currently available. The NS2B–NS3 protease is essential for viral genome replication in both viruses, increasing viral loads in infected individuals. Therefore, targeting and inhibiting this protease would significantly reduce viral replication. In a recent molecular dynamics (MD) simulation study, N-(((2,6-dibromophenyl) amino) methyl)-4-morpholinobenzamide (11q) was found to bind more strongly to the NS2B–NS3 protease of the Zika virus (ZIKV) than SYC–1307, a known ZIKV protease inhibitor. Notably, 11q was also observed to inhibit influenza virus replication. Given the high structural and sequence similarity of the NS2B–NS3 protease across ZIKV, DENV, and WNV, it was necessary to evaluate whether 11q can bind to the proteases of DENV and WNV to inhibit their activities. Using molecular docking, MD, and binding free energy studies, we found that 11q strongly binds to the NS2B–NS3 proteases of DENV and WNV with binding free energies of −15.80 ± 3.34 kcal/mol and −13.13 ± 2.56 kcal/mol, respectively. The slightly more favorable binding of 11q to the DENV protease is comparable to that observed with the ZIKV protease. Interestingly, the binding affinities of 11q for all three viral proteases surpass that of the ZIKV–SYC–1307 complex. Therefore, it is proposed that 11q may act as a pan-antiviral agent against ZIKV, DENV, and WNV proteases. However, experimental verification of its protease inhibition activities is required before it can be repurposed for therapeutic use against these viral diseases.

Graphical abstract
Keywords
Dengue virus
West Nile virus
NS2B–NS3 protease
Docking
Molecular dynamics simulation
Multiple targeting inhibitor
Funding
Nihar Ranjan Jena is thankful to the Council of Scientific and Industrial Research (CSIR, New Delhi) and the Science and Engineering Research Board (SERB, New Delhi) for the financial support (Grant No. for CSIR: 01/3061/21/ EMR-II and Grant No. for SERB: EMR/2016/005110).
Conflict of interest
The authors declare no conflicts of interest.
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