Tri- and Diterpenoids from as Inhibitors of Zika Virus Replication.

This study represents the first phytochemical analysis of () and describes new terpenoids obtained from the root bark of this species. The fractionation of the hexane extract from the root bark led to the isolation of two new 28-nor-taraxarenes derivatives, loranthones A and B ( and ), four new tigliane diterpenes (-), three known tigliane diterpenes (-), and three known flexibilene diterpenes, tonantzitlolones A-C (-). The investigation of these compounds and the use of a molecular networking-based prioritization approach afforded two other new 28-nor-taraxarenes, loranthones C and D ( and ). The cytotoxicity of compounds , , and - was evaluated against Vero cells, and their 20% cytotoxic concentration (CC) values varied from 8.7 to 328 μM; antiviral activity was tested against an epidemic Zika virus (ZIKV) strain circulating in Brazil. Six out of 12 compounds (, , -, and ) exhibited significant antiviral effects against ZIKV. Specifically, compounds and offered the most promise as lead compounds as they had a 1.7 and 1.8 log TCID/mL reduction in ZIKV replication, respectively. Together, the present findings have identified terpenoids as potent anti-ZIKV inhibitors and pave the way to the development of possible new treatments against this devastating pathogen.