Molecules, Vol. 28, Pages 974: Lichen-Derived Diffractaic Acid Inhibited Dengue Virus Replication in a Cell-Based System

Molecules, Vol. 28, Pages 974: Lichen-Derived Diffractaic Acid Inhibited Dengue Virus Replication in a Cell-Based System

Molecules doi: 10.3390/molecules28030974

Authors: Naphat Loeanurit Truong Lam Tuong Van-Kieu Nguyen Vipanee Vibulakhaophan Kowit Hengphasatporn Yasuteru Shigeta Si Xian Ho Justin Jang Hann Chu Thanyada Rungrotmongkol Warinthorn Chavasiri Siwaporn Boonyasuppayakorn

Dengue is a mosquito-borne flavivirus that causes 21,000 deaths annually. Depsides and depsidones of lichens have previously been reported to be antimicrobials. In this study, our objective was to identify lichen-derived depsides and depsidones as dengue virus inhibitors. The 18 depsides and depsidones of Usnea baileyi, Usnea aciculifera, Parmotrema dilatatum, and Parmotrema tsavoense were tested against dengue virus serotype 2. Two depsides and one depsidone inhibited dengue virus serotype 2 without any apparent cytotoxicity. Diffractaic acid, barbatic acid, and Parmosidone C were three active compounds further characterized for their efficacies (EC50), cytotoxicities (CC50), and selectivity index (SI; CC50/EC50). Their EC50 (SI) values were 2.43 ± 0.19 (20.59), 0.91 ± 0.15 (13.33), and 17.42 ± 3.21 (8.95) μM, respectively. Diffractaic acid showed the highest selectivity index, and similar efficacies were also found in dengue serotypes 1–4, Zika, and chikungunya viruses. Cell-based studies revealed that the target was mainly in the late stage with replication and the formation of infectious particles. This report highlights that a lichen-derived diffractaic acid could become a mosquito-borne antiviral lead as its selectivity indices ranged from 8.07 to 20.59 with a proposed target at viral replication.