Anti-Dengue Activity of Revaprazan Hydrochloride: A Repurposed Drug Candidate

Abstract

Dengue fever is a major health problem, and there are no vaccines or effective antiviral treatments. Drug repurposing is a quick and appealing innovative therapeutic strategy. This study aims to develop a potent anti-dengue drug for the treatment of dengue infections. In this study, we screened a library containing 174 compounds using foci-forming unit reduction and quantitative real-time polymerase chain reaction assays. Revaprazan hydrochloride showed the most potent anti-dengue activity and low cytotoxicity in Vero cells with a half-maximal inhibitory concentration (IC₅₀) of 1.36 ± 0.16 µM, and a half-maximal cytotoxicity concentration (CC₅₀) of 42.41 ± 0.05 µM. Revaprazan hydrochloride revealed 98.31% virucidal activity and 99.80% for post-infection activity against dengue virus serotype 3 (DENV-3). Revaprazan hydrochloride required only 5 min to exert its virucidal effects after contact with DENV-3. Time-of-drug addition and time-of-drug elimination assays indicated that revaprazan hydrochloride was able to interfere with the early stage of DENV-3 infection. In silico studies demonstrated that revaprazan hydrochloride had strong binding energy to the RNA-dependent RNA polymerase domain of the NS5 and the helicase domain of the NS2B/NS3 protein. DENV-3 showed no resistance up to 25 passages in the presence of revaprazan hydrochloride. Revaprazan hydrochloride showed varying inhibitory effects against all four dengue virus serotypes. Overall, revaprazan hydrochloride is a novel dengue virus inhibitor and could serve as a promising antiviral drug for further preclinical evaluations.