7D, a small molecule inhibits dengue infection by increasing interferons and neutralizing antibodies

ABSTRACT: There are a limited number of effective vaccines against dengue virus (DENV) and significant efforts are being made to develop potent anti-virals. Previously, we described that platelet-chemokine CXCL4 negatively regulates interferon (IFN)-α/β synthesis and promotes DENV2 replication. An antagonist to CXCR3(CXCL4 receptor) reversed it and inhibited viral replication. In a concurrent search, we identified CXCR3-antagonist from our compound library, namely 7D, which inhibited all serotypes of DENV in vitro. With a half-life of ~2.85hr in plasma and no significant toxicity, 7D supplementation(8mg/kg-body-weight) to DENV2-infected IFNα/β/γR-/-AG129 or wild-type C57BL6 mice increased synthesis of IFN-α/β and IFN-λ, and rescued disease symptoms like thrombocytopenia, leukopenia and vascular-le

SUBMITTER: Kishan, K Gaur 

PROVIDER: S-SCDT-10_1038-S44321-024-00137-8 | biostudies-other |

REPOSITORIES: biostudies-other