New Inhibitors of the DENV-NS5 RdRp from Carpolepis laurifolia as Potential Antiviral Drugs for Dengue Treatment

Since a few decades the dengue virus became a major public health concern and no treatment is available yet. In order to propose potential antidengue compounds for chemotherapy we focused on DENV RNA polymerase (DENV-NS5 RdRp) which is specific and essential for the virus replication. Carpolepis laurifolia belongs to the Myrtaceae and is used as febrifuge in traditional kanak medicine. Leaf extract of this plant has been identified as a hit against the DENV-NS5 RdRp. Here we present a bioguided fractionation of the leaf extract of C. laurifolia which is also the first phytochemical evaluation of this plant. Five flavonoids, namely quercetin (1), 6-methylapigenin-7-methylether (2), avicularin (3), quercitrin (4) and hyperoside (5), together with betulinic acid (6), were isolated from the leaf extract of C. laurifolia. All isolated compounds were tested individually against the DENV-NS5 RdRp and compared with four other commercial flavonoids: isoquercitrin (7), spiraeoside (8), quercetin-3,4’-di-O-glucoside (9) and rutin (10). Compounds 3, 4, 6, 8 and 10 displayed IC50 ranging from 1.7 to 2.1 μM, and were the most active against the DENV-NS5 RdRp.