1Ramdeen, S. J., 1Usoro, N., 1Giordano, K., 1Garza, P. E., 2Quadri, O., 3Esan, T. E., and *1Olanrewaju,A. A.
1Texas State University, Medical Laboratory Science Program San Marcos, TX USA
2Northern Illinois University, Chemistry and Biochemistry Analytical Lab, Dekalb, IL USA
3Rosalind Franklin University of Medicine and Science, Chicago, IL USA *Correspondence to: dep112@txstate.edu; Phone: +1 571-228-0537
Abstract:
Background: Dengue, a mosquito-borne virus infection, reportedly affected over 7.6 million people in early 2024, subsequently leading to approximately 3000 deaths. Dengue is primarily spread by Aedes (A. aegypti and A. albopictus) mosquitoes. There is currently no clinically approved preventive vaccine against Dengue virus (DENV), and according to the Center for Disease Control (CDC), the only acceptable vaccine for DENV is Dengvaxia, which has efficacy and safety issues. This makes it unsuitable for use against DENV. Drug repurpose is an alternative approach for the discovery of novel therapeutics.
Methodology: In this study, we screened over one million compounds in the zinc database against the DENV NS2B/NS3 protease (PDB ID: 2FOM). Screening yielded about 122 compounds with potential activity against DENV. Among the 122 compounds, the top four were selected based on their docking scores and commercial availability. The cytotoxicity study showed that a concentration of up to 100 µM was non-toxic. Based on the cytotoxicity results, we selected non-toxic concentrations (500nM, 1µM, 10µM, and 20µM) to test against DENV2 infection. The results were analyzed using RT-qPCR and plaque assays.
Results: Compound treatment before DENV2 infection leads to a significant reduction in viral replication, which confirms the screening result. This gives a promising platform against DENV2 therapy.
Conclusion: This shows a significant step towards the discovery of an antiviral drug against the dengue virus.
Key words: Dengue virus, Antiviral compound, Repurposing, Molecular docking, Therapeutics
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