HES-SO Valais-Wallis, Institute of Life Technologies, Sion, Switzerland.
Front Immunol. 2019 Jun 21;10:1366. doi: 10.3389/fimmu.2019.01366. eCollection 2019.
Lower respiratory infection caused by human pathogens such as influenza and respiratory syncytial virus (RSV) is a significant healthcare burden that must be addressed. The preferred options to achieve this goal are usually to develop vaccines for prophylaxis and to develop antiviral small molecules to treat infected patients with convenient, orally administrable drugs. However, developing a vaccine against RSV poses special challenges with the diminished immune system of infants and the elderly, and finding a universal flu vaccine is difficult because the product must target a large array of viral strains. On the other hand, the use of small-molecule antivirals can result in the emergence of resistant viruses as it has well-been reported for HIV, influenza, and hepatitis C virus (HCV). This paper reviews peptide antiviral strategies as an alternative to address these challenges. The discovery of influenza and RSV peptidic fusion inhibitors will be discussed and compared to small molecules in view of escape mutations. The importance of constraining peptides into macrocycles to improve both their inhibitory activity and pharmacological properties will be highlighted.
由流感和呼吸道合胞病毒（RSV）等人类病原体引起的下呼吸道感染是一个重大的医疗保健负担，必须加以解决。实现这一目标的首选方案通常是开发预防疫苗和开发抗病毒小分子，以便用方便的口服药物治疗感染患者。然而，针对 RSV 开发疫苗具有特殊的挑战，因为婴儿和老年人的免疫系统减弱，而且由于产品必须针对大量的病毒株，因此很难找到通用的流感疫苗。另一方面，正如已报道的 HIV、流感和丙型肝炎病毒（HCV）所表明的那样，小分子抗病毒药物的使用会导致耐药病毒的出现。本文综述了作为解决这些挑战的替代方法的肽类抗病毒策略。将讨论流感和 RSV 肽融合抑制剂的发现，并根据逃逸突变与小分子进行比较。将强调将肽约束成大环以提高其抑制活性和药理学性质的重要性。
