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基于结构的抗病毒肽的计算机设计,针对发热伴血小板减少综合征病毒糖蛋白 Gn。

In Silico Structure-Based Design of Antiviral Peptides Targeting the Severe Fever with Thrombocytopenia Syndrome Virus Glycoprotein Gn.

机构信息

State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.

Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 571199, China.

出版信息

Viruses. 2021 Oct 11;13(10):2047. doi: 10.3390/v13102047.

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus in Asia that causes severe disease. Despite its clinical importance, treatment options for SFTSV infection remains limited. The SFTSV glycoprotein Gn plays a major role in mediating virus entry into host cells and is therefore a potential antiviral target. In this study, we employed an in silico structure-based strategy to design novel cyclic antiviral peptides that target the SFTSV glycoprotein Gn. Among the cyclic peptides, HKU-P1 potently neutralizes the SFTSV virion. Combinatorial treatment with HKU-P1 and the broad-spectrum viral RNA-dependent RNA polymerase inhibitor favipiravir exhibited synergistic antiviral effects in vitro. The in silico peptide design platform in this study may facilitate the generation of novel antiviral peptides for other emerging viruses.

摘要

严重发热伴血小板减少综合征病毒(SFTSV)是亚洲地区一种新兴的蜱传布尼亚病毒,可引起严重疾病。尽管其具有临床重要性,但SFTSV 感染的治疗选择仍然有限。SFTSV 糖蛋白 Gn 在介导病毒进入宿主细胞中起着重要作用,因此是一个潜在的抗病毒靶点。在这项研究中,我们采用基于结构的计算策略设计了针对 SFTSV 糖蛋白 Gn 的新型环状抗病毒肽。在这些环状肽中,HKU-P1 可有效中和 SFTSV 病毒粒子。HKU-P1 与广谱病毒 RNA 依赖性 RNA 聚合酶抑制剂法匹拉韦联合治疗在体外表现出协同抗病毒作用。本研究中的计算肽设计平台可能有助于为其他新兴病毒生成新型抗病毒肽。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f9/8539749/381dbf30a028/viruses-13-02047-g001.jpg

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