A Broad-Spectrum Antiviral Peptide Blocks Infection of Viruses by Binding to Phosphatidylserine in the Viral Envelope.

A Broad-Spectrum Antiviral Peptide Blocks Infection of Viruses by Binding to Phosphatidylserine in the Viral Envelope.
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一种广谱抗病毒肽通过与病毒包膜中的磷脂酰丝氨酸结合来阻断病毒感染。

DOI:
10.3390/cells9091989
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发表时间:
2020-08-29
期刊:
影响因子:
6
通讯作者:
Wiertz EJHJ
Wiertz EJHJ
中科院分区:
生物学2区
文献类型:
--
作者:
Luteijn RD;Praest P;Thiele F;Sadasivam SM;Singethan K;Drijfhout JW;Bach C;de Boer SM;Lebbink RJ;Tao S;Helfer M;Bach NC;Protzer U;Costa AI;Killian JA;Drexler I;Wiertz EJHJ

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病毒感染的持续威胁和抗病毒药物耐药性的出现,需要不断寻找新的抗病毒化合物。作用于许多病毒共有成分的广谱抑制化合物是很有希望的抗病毒候选药物。在这里,我们鉴定了一种源自牛痘病毒蛋白CPXV012的多肽,它是一种广谱抗病毒多肽。我们发现,CPXV012多肽可以阻止多种临床和经济上重要的包膜病毒的感染,包括痘病毒、单纯疱疹病毒-1、乙肝病毒、艾滋病毒-1和裂谷热病毒。感染非包膜病毒,如柯萨奇B3病毒和腺病毒不受影响。这些结果进一步表明,病毒颗粒通过与CPXV012多肽的直接相互作用而被中和,这种阳离子多肽可能特异性地结合并破坏由阴离子磷脂磷脂酰丝氨酸组成的膜,磷脂酰丝氨酸是许多病毒膜的重要组成部分。这些结果有力地表明,CPXV012肽通过与病毒被膜中的磷脂酰丝氨酸直接相互作用来抑制病毒感染。这些结果重申了阳离子多肽作为广泛作用的病毒抑制剂的潜力。
The ongoing threat of viral infections and the emergence of antiviral drug resistance warrants a ceaseless search for new antiviral compounds. Broadly-inhibiting compounds that act on elements shared by many viruses are promising antiviral candidates. Here, we identify a peptide derived from the cowpox virus protein CPXV012 as a broad-spectrum antiviral peptide. We found that CPXV012 peptide hampers infection by a multitude of clinically and economically important enveloped viruses, including poxviruses, herpes simplex virus-1, hepatitis B virus, HIV-1, and Rift Valley fever virus. Infections with non-enveloped viruses such as Coxsackie B3 virus and adenovirus are not affected. The results furthermore suggest that viral particles are neutralized by direct interactions with CPXV012 peptide and that this cationic peptide may specifically bind to and disrupt membranes composed of the anionic phospholipid phosphatidylserine, an important component of many viral membranes. The combined results strongly suggest that CPXV012 peptide inhibits virus infections by direct interactions with phosphatidylserine in the viral envelope. These results reiterate the potential of cationic peptides as broadly-acting virus inhibitors.
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