邻氨基苯甲酰胺肽模拟物对单纯疱疹病毒1型和一种冠状病毒的抗病毒活性

Antiviral Activity of Anthranilamide Peptidomimetics against Herpes Simplex Virus 1 and a Coronavirus.

作者信息

Urmi Umme Laila, Attard Samuel, Vijay Ajay Kumar, Willcox Mark D P, Kumar Naresh, Islam Salequl, Kuppusamy Rajesh

机构信息

School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia.

School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.

出版信息

Antibiotics (Basel). 2023 Sep 12;12(9):1436. doi: 10.3390/antibiotics12091436.

DOI:10.3390/antibiotics12091436

PMID:37760732

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10525570/

Abstract

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of 17 short anthranilamide-based peptidomimetic compounds against two viruses: Murine hepatitis virus 1 (MHV-1) which is a surrogate of human coronaviruses and herpes simplex virus 1 (HSV-1). The half-maximal inhibitory concentration (IC) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds and displayed the most potent inhibitory effects with IC values of 2.38 μM, and 6.3 μM against MHV-1 while compounds and showed IC values of 14.8 μM and 13 μM against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

摘要

开发有效的抗病毒药物对于应对全球病毒感染负担至关重要。传统的抗病毒药物开发涉及针对特定的病毒蛋白，这可能导致耐药菌株的出现。为了探索替代策略，我们研究了抗菌肽模拟化合物的抗病毒潜力。在本研究中，我们评估了17种基于邻氨基苯甲酰胺的短肽模拟化合物对两种病毒的抗病毒潜力：鼠肝炎病毒1型（MHV-1），它是人类冠状病毒的替代物，以及单纯疱疹病毒1型（HSV-1）。在体外测定这些化合物的半数最大抑制浓度（IC）值，以评估它们作为抗病毒药物的效力。化合物和表现出最有效的抑制作用，对MHV-1的IC值分别为2.38 μM和6.3 μM，而化合物和对HSV-1的IC值分别为14.8 μM和13 μM。通过透射电子显微镜（TEM）获得的多项抗病毒评估和微观图像共同表明，这些化合物对病毒包膜有直接影响。基于这一结果，可以得出结论，肽模拟化合物可为开发有效的抗病毒药物提供一种新方法。