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二聚肽(KKYRYHLKPF)K 通过抑制基孔肯雅热和寨卡病毒感染的不同步骤显示出广谱抗病毒活性。

The Dimeric Peptide (KKYRYHLKPF)K Shows Broad-Spectrum Antiviral Activity by Inhibiting Different Steps of Chikungunya and Zika Virus Infection.

机构信息

Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil.

School of Pharmaceutical Sciences, São Paulo State University, Araraquara 14800-903, SP, Brazil.

出版信息

Viruses. 2023 May 14;15(5):1168. doi: 10.3390/v15051168.

DOI:10.3390/v15051168
PMID:37243254
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10222827/
Abstract

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I)K [(KKYRYHLKPF)K], a peptide derived from the Bothropstoxin-I toxin in the venom of the snake, showed antiviral activity against SARS-CoV-2. In this study, we assessed the activity of this peptide against CHIKV and ZIKV and its antiviral action in the different stages of the viral replication cycle in vitro. We observed that (p-BthTX-I)K impaired CHIKV infection by interfering with the early steps of the viral replication cycle, reducing CHIKV entry into BHK-21 cells specifically by reducing both the attachment and internalization steps. (p-BthTX-I)K also inhibited the ZIKV replicative cycle in Vero cells. The peptide protected the cells against ZIKV infection and decreased the levels of the viral RNA and the NS3 protein of this virus at viral post-entry steps. In conclusion, this study highlights the potential of the (p-BthTX-I)K peptide to be a novel broad-spectrum antiviral candidate that targets different steps of the replication cycle of both CHIKV and ZIKV.

摘要

基孔肯雅病毒(CHIKV)和寨卡病毒(ZIKV)是全球重要的致病病原体。目前,尚无针对这些病毒的批准的抗病毒药物或疫苗。然而,肽已显示出在新药开发方面的巨大潜力。最近的一项研究描述了来源于蛇毒的 Bothropstoxin-I 毒素的肽(p-BthTX-I)K [(KKYRYHLKPF)K]对 SARS-CoV-2 具有抗病毒活性。在这项研究中,我们评估了该肽对 CHIKV 和 ZIKV 的活性及其在体外病毒复制周期的不同阶段的抗病毒作用。我们观察到,(p-BthTX-I)K 通过干扰病毒复制周期的早期步骤来损害 CHIKV 感染,特别是通过减少附着和内化步骤来减少 CHIKV 进入 BHK-21 细胞。(p-BthTX-I)K 还抑制了 Vero 细胞中的 ZIKV 复制周期。该肽可保护细胞免受 ZIKV 感染,并降低病毒进入后步骤中该病毒的 RNA 和 NS3 蛋白的水平。总之,这项研究强调了(p-BthTX-I)K 肽作为一种新型广谱抗病毒候选药物的潜力,该药物可针对 CHIKV 和 ZIKV 的复制周期的不同步骤发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add7/10222827/06f2ea5ff9d1/viruses-15-01168-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add7/10222827/f0d616d6bbf1/viruses-15-01168-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add7/10222827/7014b73e67de/viruses-15-01168-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add7/10222827/4c3a2db732f7/viruses-15-01168-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add7/10222827/06f2ea5ff9d1/viruses-15-01168-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add7/10222827/f0d616d6bbf1/viruses-15-01168-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add7/10222827/7014b73e67de/viruses-15-01168-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add7/10222827/4c3a2db732f7/viruses-15-01168-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add7/10222827/06f2ea5ff9d1/viruses-15-01168-g004.jpg

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