Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids.
Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids.
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DOI：
10.3390/ph14040304
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发表时间：
2021-03-31
期刊：
影响因子：
--
通讯作者：
Barron AE
中科院分区：
文献类型：
--
作者：
Diamond G;Molchanova N;Herlan C;Fortkort JA;Lin JS;Figgins E;Bopp N;Ryan LK;Chung D;Adcock RS;Sherman M;Barron AE
病毒感染，如由单纯疱疹病毒-1（HSV-1）和SARS-CoV-2引起的病毒感染，每年影响数百万人。然而，很少有抗病毒药物可以有效治疗这些感染。抗病毒药物开发的标准方法包括识别独特的病毒靶点，然后设计针对该靶点的药物。抗菌肽是一种新型的抗病毒药物。AMP已经显示通过破坏病毒包膜而使许多不同的包膜病毒变性。然而，AMP作为抗微生物治疗剂的临床开发受到许多因素的阻碍，特别是它们作为肽的酶不稳定结构。我们研究了AMP类肽模拟物（序列特异性N-取代甘氨酸寡聚体）的抗病毒潜力。这些类肽具有对蛋白酶不敏感的明显优势，并且还表现出增加的生物利用度和稳定性。我们的研究结果表明，几个类肽表现出有效的体外抗病毒活性对HSV-1和SARS冠状病毒-2感染前孵育。换句话说，它们对病毒结构有直接影响，这似乎使病毒颗粒不具有感染性。通过cryo-EM的可视化显示病毒包膜破坏类似于针对其他病毒的AMP活性所观察到的破坏。此外，我们没有观察到对口腔上皮细胞的原代培养物的细胞毒性。这些结果表明一个共同的或仿生的机制，可能是由于磷脂头基组成的病毒包膜和宿主细胞膜之间的差异，从而强调了这类分子作为安全有效的广谱抗病毒剂的潜力。我们讨论了如何以及为什么不同的分子特征之间的10个候选肽可能会影响抗病毒活性和选择性。
Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their enzymatically labile structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. In other words, they have a direct effect on the viral structure, which appears to render the viral particles non-infective. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells. These results suggest a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents. We discuss how and why differing molecular features between 10 peptoid candidates may affect both antiviral activity and selectivity.
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影响因子：
--
作者：
de la Fuente-Núñez C;Reffuveille F;Mansour SC;Reckseidler-Zenteno SL;Hernández D;Brackman G;Coenye T;Hancock RE
通讯作者：
Hancock RE
影响因子：
4.6
作者：
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通讯作者：
Barron AE
影响因子：
4
作者：
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通讯作者：
Hancock, Robert E. W.
影响因子：
7.3
作者：
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通讯作者：
Nuss, John M.
影响因子：
6
作者：
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通讯作者：
Wiertz EJHJ