Wulfenioidins D-N, Structurally Diverse Diterpenoids with Anti-Zika Virus Activity Isolated from Orthosiphon wulfenioides .

Eleven diterpenoids, wulfenioidins D-N ( 1 - 11 ), classified into five distinct carbon skeletons with one unreported framework, and four modified abietane diterpenoids were isolated from the whole plant of Orthosiphon wulfenioides . The structures and absolute configurations were characterized by spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analyses. Compounds 3 and 5 exhibited activity against Zika virus (ZIKV) with EC ₅₀ values of 8.07 and 8.50 μM, respectively, and showed no significant cytotoxicity toward Vero cells at 100 μM. Western blot and immunofluorescence experiments showed that compounds 3 and 5 interfered with the replication of the ZIKV by inhibiting the expression of the ZIKV envelope (E) protein.