Cirne-Santos Claudio C, de S Barros Caroline, Rabelo Vitor W, Esteves Priscilla O, Gomes Max W L, Teixeira Valéria L, de P Paixão Izabel C N
Acta Virol. 2021;65(4):402-410. doi: 10.4149/av_2021_406.
Zika virus (ZIKV) is an arthropod-borne flavivirus that reemerged in 2007 and, since then, has caused several outbreaks and spread to over 80 countries worldwide. Along with this, ZIKV infections have been associated with severe clinical outcomes, including neurological manifestations, especially in newborns, posing a major threat to human health. However, there are no licensed vaccines or specific antiviral agents available yet; thereby, there is an urgent need for the discovery of novel therapeutic strategies to fight this infection. In this context, seaweeds are proven sources of biologically relevant products, including antiviral ones, that remain poorly explored. Herein, we evaluated the antiviral potential of the dichloromethane extract of the red seaweed Bryotamnion triquetrum against ZIKV. MTT assay was carried out to evaluate the extract's toxicity in Vero cells, while standard plaque assays were performed for viral titer quantification in the antiviral assays. The B. triquetrum extract possessed great inhibitory activity on the ZIKV replication in Vero cells, with an EC50 of 1.38 µg/ml and a higher selectivity index than ribavirin (289.85 and 75.20, respectively), a licensed antiviral drug. The investigation of its mechanism of action revealed a moderate virucidal effect while it strongly impaired virus replication at both early and late steps of the virus replication cycle with moderate inhibition at the attachment stage. Finally, the B. triquetrum extract presented a remarkable synergistic effect with ribavirin at suboptimal concentrations, which also highlights the promising antiviral potential of this product as a drug candidate to combat ZIKV infection. Keywords: Rhodophyta; Algae; arbovirus; antiviral; Zika.
寨卡病毒（ZIKV）是一种节肢动物传播的黄病毒，于2007年再次出现，自那时以来，已引发多次疫情，并传播到全球80多个国家。与此同时，寨卡病毒感染与严重的临床后果有关，包括神经表现，尤其是在新生儿中，对人类健康构成重大威胁。然而，目前尚无获批的疫苗或特异性抗病毒药物；因此，迫切需要发现新的治疗策略来对抗这种感染。在这种背景下，海藻被证明是生物相关产品的来源，包括抗病毒产品，但仍未得到充分探索。在此，我们评估了红藻三叉仙菜二氯甲烷提取物对寨卡病毒的抗病毒潜力。采用MTT法评估提取物对Vero细胞的毒性，同时在抗病毒试验中采用标准蚀斑试验对病毒滴度进行定量。三叉仙菜提取物对Vero细胞中的寨卡病毒复制具有很强的抑制活性，半数有效浓度（EC50）为1.38µg/ml，选择性指数高于利巴韦林（分别为289.85和75.20），后者是一种获批的抗病毒药物。对其作用机制的研究表明，它具有适度的杀病毒作用，同时在病毒复制周期的早期和晚期都强烈损害病毒复制，在附着阶段有适度抑制作用。最后，三叉仙菜提取物在次优浓度下与利巴韦林呈现出显著的协同效应，这也突出了该产品作为对抗寨卡病毒感染的候选药物具有的抗病毒潜力。关键词：红藻门；藻类；虫媒病毒；抗病毒；寨卡
