Structural models for the design of novel antiviral agents against Spondweni virus helicase

Abstract

Spondweni virus (SPONV), a possible emerging virus, is a member of the Flaviviridae virus family, of the genus Flavivirus and belongs to a serogroup with the Zika virus. The latest epidemic of Zika fever, which broke out in the Western Hemisphere, warns about the risk of the corre‑ sponding urban epidemic potential of SPONV and calls for the design of anti‑SPONV therapies. Previous studies have demonstrated that viral RNA helicases represent promising pharmacological targets for antiviral drugs/inhibitors, as they are implicated in viral replication and proliferation. Therefore, the present study proposes the three‑dimensional structure of the helicase/protease enzyme of SPONV through homology modeling, using the crystal structure of the Dengue virus‑4 helicase/protease of the same viral family as a template. For the evaluation of the accuracy and reliability of the model in structure‑based drug design strategies, the crystal structure of the hepatitis C virus (HCV) helicase was used, complexed with a single‑stranded RNA, a key molecule for the establishment of interactions with a future inhibitor of the SPONV helicase. Following the evaluation of the model and the identification of motifs characteristic of the Flaviviridae family, data from previous publications on the treatment of HCV were incorporated, with the aim of detecting the ideal residues in the Spondweni model, which are similar to those of the HCV structure and are inhibitor targets. The existing pharmacophoric model was tested for its application to the Spondweni helicase model as a potential inhibitor of its func‑ tionality and potential future use in design experiments of novel anti‑SPONV agents.