Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, San Diego, California, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, California, USA.
Phytomedicine. 2024 Jan;123:155197. doi: 10.1016/j.phymed.2023.155197. Epub 2023 Nov 7.
Zika virus (ZIKV) is an emerging arbovirus that in recent years has been associated with cases of severe neurological disorders, such as microcephaly in newborns and Guillain-Barré syndrome in adults. As there is no vaccine or treatment, the search for new therapeutic targets is of great relevance. In this sense, plants are extremely rich sources for the discovery of new bioactive compounds and the species Phyllanthus brasiliensis (native to the Amazon region) remains unexplored.
To investigate the potential antiviral activity of compounds isolated from P. brasiliensis leaves against ZIKV infection.
In vitro antiviral assays were performed with justicidin B (a lignan) and four glycosylated lignans (tuberculatin, phyllanthostatin A, 5-O-β-d-glucopyranosyljusticidin B, and cleistanthin B) against ZIKV in Vero cells. MTT colorimetric assay was used to assess cell viability and plaque forming unit assay to quantify viral load. In addition, for justicidin B, tests were performed to investigate the mechanism of action (virucidal, adsorption, internalization, post-infection).
The isolated compounds showed potent anti-ZIKV activities and high selectivity indexes. Moreover, justicidin B, tuberculatin, and phyllanthostatin A completely reduced the viral load in at least one of the concentrations evaluated. Among them, justicidin B stood out as the main active, and further investigation revealed that justicidin B exerts its antiviral effect during post-infection stages, resulting in a remarkable 99.9 % reduction in viral load when treatment was initiated 24 h after infection.
Our findings suggest that justicidin B inhibits endosomal internalization and acidification, effectively interrupting the viral multiplication cycle. Therefore, the findings shed light on the promising potential of isolated compounds isolated from P. brasiliensis, especially justicidin B, which could contribute to the drug development and treatments for Zika virus infections.
寨卡病毒（ZIKV）是一种新兴的虫媒病毒，近年来与新生儿小头畸形和成人吉兰-巴雷综合征等严重神经疾病有关。由于目前尚无疫苗或治疗方法，因此寻找新的治疗靶点具有重要意义。在这方面，植物是发现新的生物活性化合物的极其丰富的来源，而巴西叶下珠（原产于亚马逊地区）这一物种尚未被开发。
研究从巴西叶下珠叶片中分离得到的化合物对寨卡病毒感染的潜在抗病毒活性。
在 Vero 细胞中，使用正义丁素（木质素）和四种糖基化木质素（薯蓣素 A、5-O-β-d-吡喃葡萄糖基正义丁素、巴西薯蓣素和 cleistanthin B）进行体外抗病毒测定，以评估化合物抗寨卡病毒的活性。MTT 比色法用于评估细胞活力，噬斑形成单位测定法用于定量病毒载量。此外，还针对正义丁素进行了作用机制（病毒杀伤、吸附、内化、感染后）的检测。
分离得到的化合物表现出很强的抗寨卡病毒活性和很高的选择性指数。此外，至少在评估的浓度之一中，正义丁素、薯蓣素和巴西薯蓣素完全降低了病毒载量。其中，正义丁素表现出最强的活性，进一步的研究表明，正义丁素在感染后阶段发挥其抗病毒作用，在感染后 24 小时开始治疗时，病毒载量显著降低了 99.9%。
我们的研究结果表明，正义丁素抑制内体内化和酸化，有效阻断病毒的复制周期。因此，这些发现揭示了巴西叶下珠中分离得到的化合物具有很大的应用潜力，特别是正义丁素，可能有助于寨卡病毒感染的药物研发和治疗。
