Dengue infection is a global burden affecting millions of world population. Previous studies indicated that flavanones were potential dengue virus inhibitors. We discovered that a novel flavanone derivative, 5-hydroxy-7-methoxy-6-methylflavanone (FN5Y), inhibited DENV2 pH-dependent fusion in cell-based system with strong binding efficiency to DENV envelope protein at K (P83, L107, K128, L198), K' (T48, E49, A50, L198, Q200, L277), X' (Y138, V354, I357), and Y' (V97, R99, N103, K246) by molecular dynamic simulation. FN5Y inhibited DENV2 infectivity with EC₅₀s (and selectivity index) of 15.99 ± 5.38 (>6.25), and 12.31 ± 1.64 (2.23) μM in LLC/MK2 and Vero cell lines, respectively, and inhibited DENV4 at 11.70 ± 6.04 (>8.55) μM. CC50s in LLC/MK2, HEK-293, and HepG2 cell lines at 72 h were higher than 100 μM. Time-of-addition study revealed that the maximal efficacy was achieved at early after infection corresponded with pH-dependent fusion. Inactivating the viral particle, interfering with cellular receptors, inhibiting viral protease, or the virus replication complex were not major targets of this compound. FN5Y could become a potent anti-flaviviral drug and can be structurally modified for higher potency using simulation to DENV envelope as a molecular target.

登革热感染是影响全球数百万人口的全球性负担。先前的研究表明，黄烷酮是潜在的登革热病毒抑制剂。我们发现一种新型的黄烷酮衍生物5-羟基-7-甲氧基-6-甲基黄烷酮（FN5Y）抑制DENV2 pH依赖性融合在基于细胞的系统中对K处的DENV包膜蛋白具有很强的结合效率（P83，L107，K128 ，L198），K'（T48，E49，A50，L198，Q200，L277），X'（Y138，V354，I357）和Y'（V97，R99，N103，K246）。FN5Y通过EC ₅₀抑制DENV2感染s（和选择性指数）在LLC / MK2和Vero细胞系中分别为15.99±5.38（> 6.25）和12.31±1.64（2.23）μM，并在11.70±6.04（> 8.55）μM处抑制DENV4。LLC / MK2，HEK-293和HepG2细胞系在第72小时的CC50高于100μM。添加时间研究表明，在感染后的早期达到了最大功效，这与pH依赖性融合相对应。使病毒颗粒失活，干扰细胞受体，抑制病毒蛋白酶或病毒复制复合物不是该化合物的主要目标。FN5Y可能成为有效的抗黄病毒药物，并且可以通过模拟DENV包膜作为分子靶点进行结构修饰以获得更高的效力。