Abstract:
In an extensive screening endeavor for anti-coronaviral compounds, we examined 824 tropical plant extracts from the Annonaceae and Rutaceae families. The screening identified an ethyl acetate extract from the aerial parts of Miliusa balansae for its potent inhibitory activity against Human coronavirus HCoV-229E. Subsequent bioassay-guided fractionation of this extract revealed two unreported miliusanes including a complex dimeric structure and seven known compounds, comprising miliusane XXXVI, (+)-miliusol, bistyryls, styryl-pyranones, and the flavonoid rhamnetin. The absolute configuration of the new dimeric miliusane was determined by X-ray crystallography and a putative biogenetic origin was proposed. Investigation of the antiviral effect of these nine phytochemicals within HCoV-229E-infected Huh-7 cells showed that (+)-miliusol and miliusane XXXVI exert antiviral activity at non-cytotoxic concentrations, with IC50 values of 1.15 μM and 19.20 μM, respectively. Furthermore, these compounds significantly inhibited SARS-CoV-2 infection in Vero cells, presenting IC50 values of 11.31 μM for (+)-miliusol and 17.92 μM for miliusane XXXVI. Additionally, both compounds exhibited a potent antiviral effect against the emergent mosquito-borne Zika virus, with IC50 values of 1.34 μM and 23.45 μM, respectively. Time-of-addition assays suggest that their mechanism of action might target later stages of the viral cycle, indicating potential modulation of specific cellular pathways. These findings reinforce the invaluable contribution of medicinal flora as reservoirs of natural antiviral agents and emphasize their prospective role in combatting viruses of medical interest.
摘要:
在抗冠状病毒化合物的广泛筛选工作中,我们检查了番荔枝科和露树科的824种热带植物提取物。筛选确定了来自Miliusabalansae地上部分的乙酸乙酯提取物,具有对人冠状病毒HCoV-229E的有效抑制活性。随后对该提取物进行生物测定指导的分级分离,发现了两种未报道的米利usanes,包括复杂的二聚体结构和七个已知化合物。包括MiliusaneXXXVI,(+)-miliusol,bistyryls,苯乙烯基吡喃酮,还有类黄酮鼠李糖素.通过X射线晶体学确定了新的二聚体miliusane的绝对构型,并提出了推定的生物起源。对HCoV-229E感染的Huh-7细胞中这9种植物化学物质的抗病毒作用的研究表明,()-米利素和米利素XXXVI在非细胞毒性浓度下发挥抗病毒活性,IC50值为1.15μM和19.20μM,分别。此外,这些化合物显著抑制SARS-CoV-2在Vero细胞中的感染,(+)-miliusol的IC50值为11.31μM,miliusaneXXXVI的IC50值为17.92μM。此外,这两种化合物都对紧急的蚊媒寨卡病毒表现出有效的抗病毒作用,IC50值为1.34μM和23.45μM,分别。添加时间测定表明,它们的作用机制可能针对病毒周期的后期阶段,表明特定细胞途径的潜在调节。这些发现加强了药用植物作为天然抗病毒剂储库的宝贵贡献,并强调了它们在对抗医学病毒中的潜在作用。