Exploring the potential therapeutic effects of ultradiluted Crotalus horridus on antibody-dependent enhancement in dengue virus pathogenesis.

DENV remains a global health concern, with ADE playing a major role in severe disease progression. ADE leads to excessive cytokine release, nitric oxide overproduction, and elevated levels of non-structural-1 antigen, contributing to higher vascular dysfunction, thrombocytopenia, and hemorrhagic manifestations. The present study investigated the therapeutic effect of ultradiluted Crotalus horridus on ADE-mediated DENV infection using in vitro system. MTT, colony formation, cytopathic effect observation, ELISA, and qRT-PCR, were performed to assess cytotoxicity, viral pathogenesis, and immunomodulatory effects. Ultradiluted Crotalus horridus showed no cytotoxicity at lower concentrations and preserved cell viability. Therapeutic treatment altered the expression of pro-inflammatory and anti-inflammatory mediators in HepG2 cells infected with DENV under ADE conditions. Furthermore, nitric oxide levels and non-structural 1 antigen secretion were significantly decreased, indicating a reduction in viral replication and associated pathogenic immunomodulation. Our study also revealed that the expression of TLRs were significantly downregulated during ADE of DENV infection. Following treatment with ultradiluted Crotalus horridus, TLR expression was enhanced, which might have aggravated the immune response during ADE in DENV infection. In conclusion, these findings demonstrate that ultradiluted Crotalus horridus may act as a potential therapeutic drug to alleviate the severity associated with ADE-mediated infection.