Sinococuline, a bioactive compound of Cocculus hirsutus has potent anti-dengue activity

Abstract

Dengue virus (DENV) infection has increased worldwide, with over 400 million infections annually, and has become a serious public health concern. Several drug candidates, new and repurposed, have failed to meet the primary efficacy endpoints. We have recently shown that Aqueous Extract of the stem of Cocculus hirsutus (AQCH) was effective in vitro and in vivo against DENV and was safe in humans. We now report that an active ingredient of AQCH, Sinococuline, protects against the antibody-mediated secondary-DENV infection in the AG129 mouse model. DENV infection markers were assessed, viz. serum viremia and vital organs pathologies-viral load, proinflammatory cytokines and intestinal vascular leakage. The treatment with Sinococuline at 2.0 mg/kg/day; BID (twice a day), was the most effective in protecting the severely DENV-infected AG129 mice. Also, this dose effectively reduced serum viremia and tissue-viral load and inhibited the elevated expression levels of proinflammatory cytokines (TNF-α and IL-6) in several vital organs. Based on these findings, it could be explored further for pre-clinical and clinical developments for the treatment of dengue.

ADPDB: A Comprehensive Knowledgebase of Manually Curated Peptides Against Dengue Virus

“…Surprisingly, even though they are distinct, they all cause similar sicknesses. People infected with any of these types may experience a range of symptoms, from asymptomatic fever to things like joint pain, rash, and other mild issues.It may also result in life-threatening symptoms like dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) in severe cases (Shukla et al, 2023). The most important thing to note regarding these serotypes is that the infection with one induces lifelong immunity against only itself and not the other three serotypes.…”