6,6′-dihydroxythiobinupharidine

6,6′-Dihydroxythiobinupharidine (DTBN) is a dimeric sesquiterpene thioalkaloid isolated from the plant Nuphar lutea. It is a pleiotropic small molecule with distinct inhibitory actions on several cellular enzymes and pathogens. DTBN potently inhibits certain human cysteine proteases, specifically showing highest potency against Cathepsin S, and to a lesser extent Cathepsin L and Cathepsin B. It also inhibits viral replication of SARS-CoV-2 in both in vitro cell models and in vivo mouse models, although it does not inhibit the SARS-CoV-2 main protease (Mpro). Its mechanisms include covalent inhibition of cysteine proteases through disulfide bond formation at the active site cysteine, direct inhibition of viral RNA-dependent RNA polymerase (RdRp), and reported inhibition of host proteins such as conventional protein kinase C isoforms (PKCα, PKCγ), type II DNA topoisomerase, and NF-κB signaling. In preclinical studies, DTBN demonstrated both anti-viral and anti-inflammatory activities, reducing SARS-CoV-2 viral load and lung damage in infected mice. DTBN represents a promising lead natural product for anti-infective and anti-inflammatory drug development[1][2].

Other names

6,6′-dihydroxythiobinupharidine