Shilovskiy I P, Andreev S M, Kozhikhova K V, Nikolskii A A, Khaitov M R
National Research Center-Institute of Immunology, Federal Medical-Biological Agency.
Mol Biol (Mosk). 2019 Jul-Aug;53(4):541-560. doi: 10.1134/S002689841904013X.
The human respiratory syncytial virus (RSV) is one of the most common viral pathogens that affects the lower respiratory tract and could be a reason of bronchiolitis and/or pneumonia. Currently, there are no available effective ways of treating the RSV infection. Attempts to develop preventive vaccine have been unsuccessful. The only therapeutic agent used for RSV treatment is virazole (ribavirin); however, it induces adverse effects. Medications based on neutralizing monoclonal antibodies, such as IGIV (Respigam), palivizumab (Synagis), and MEDI-524 (Numab), are under clinical trials; however, their use will be limited by their high cost. One of the promising approaches for antiviral therapy is the use of natural peptides (defensins and cathelicidins), or their synthetic analogs. The majority of currently described antiviral peptides are developed against the human immunodeficiency virus, the herpes simplex virus, and the influenza virus. At the same time, a body of experimental data evidencing anti-RSV activity of peptides has been accumulated. The main advantages of peptide drugs are their wide spectrum of antiviral activity and low toxicity. However, there are obstacles in implementing peptide-based drugs in clinical practice. Due to their low resistance to the action of serum proteases, most authors consider peptides promising only for local application. Given that RSV affects the epithelium of the respiratory tract, where the protease activity is lower than in the systemic circulation, it is possible to develop locally active peptide drugs, for example, as inhalation forms. Their stability could also be increased by the synthesis of dendrimer peptides and by the development of recombinant peptides as precursor proteins. Anti-RSV peptides can be divided into several groups: (1) attachment and/or fusion blockers; (2) peptides displaying direct virucidal activity, disrupting the viral envelope. Such peptides, which suppress early stages of the viral life cycle, are considered prophylactic agents. However, for several peptides, their immunoregulatory properties have been described, which opens the possibility for therapeutic use. This review summarizes the information on the antiviral properties of such peptides and mechanisms of their action and describes the prospects of the future development of antiviral peptides.
人呼吸道合胞病毒（RSV）是影响下呼吸道的最常见病毒病原体之一，可能是细支气管炎和/或肺炎的病因。目前，尚无有效的治疗RSV感染的方法。开发预防性疫苗的尝试一直未成功。用于RSV治疗的唯一治疗药物是病毒唑（利巴韦林）；然而，它会引起不良反应。基于中和单克隆抗体的药物，如IGIV（Respigam）、帕利珠单抗（Synagis）和MEDI-524（Numab），正在进行临床试验；然而，它们的使用将因其高成本而受到限制。抗病毒治疗的一种有前景的方法是使用天然肽（防御素和cathelicidins）或其合成类似物。目前描述的大多数抗病毒肽是针对人类免疫缺陷病毒、单纯疱疹病毒和流感病毒开发的。与此同时，已经积累了一系列证明肽具有抗RSV活性的实验数据。肽类药物的主要优点是其广泛的抗病毒活性和低毒性。然而，在临床实践中应用基于肽的药物存在障碍。由于它们对血清蛋白酶作用的抵抗力较低，大多数作者认为肽仅适用于局部应用。鉴于RSV影响呼吸道上皮，那里的蛋白酶活性低于体循环，有可能开发局部活性肽药物，例如吸入剂型。通过合成树枝状聚合物肽和开发作为前体蛋白的重组肽，也可以提高它们的稳定性。抗RSV肽可分为几组：（1）附着和/或融合阻断剂；（2）具有直接杀病毒活性、破坏病毒包膜的肽。这类抑制病毒生命周期早期阶段的肽被视为预防剂。然而，对于几种肽，已经描述了它们的免疫调节特性，这为治疗用途开辟了可能性。本综述总结了关于此类肽的抗病毒特性及其作用机制的信息，并描述了抗病毒肽未来发展的前景。
