Department of Microbiology and Parasitology, Faculty of Medicine, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
Pharmaceutical Chemistry Department, University of Kansas, Douglas, KS, United States.
Front Cell Infect Microbiol. 2023 Apr 20;13:1125135. doi: 10.3389/fcimb.2023.1125135. eCollection 2023.
Acute respiratory infections are a group of diseases caused by viruses, bacteria, and parasites that mainly affect children until the age of 5 and immunocompromised senior adults. In Mexico, these infections are the main cause of morbidity in children, with more than 26 million cases of respiratory infections reported by the Secretariat of Health, in 2019. The human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV), and the human parainfluenza-2 (hPIV-2) are responsible for many respiratory infections. Currently, palivizumab, a monoclonal antibody against the fusion protein F, is the treatment of choice against hRSV infections. This protein is being studied for the design of antiviral peptides that act by inhibiting the fusion of the virus and the host cell. Therefore, we examined the antiviral activity of the HRA2pl peptide, which competes the heptad repeat A domain of the F protein of hMPV. The recombinant peptide was obtained using a viral transient expression system. The effect of the fusion peptide was evaluated with an entry assay. Moreover, the effectiveness of HRA2pl was examined in viral isolates from clinical samples obtained from patients with infections caused by hRSV, hMPV, or hPIV-2, by evaluating the viral titer and the syncytium size. The HRA2pl peptide affected the viruses' capacity of entry, resulting in a 4-log decrease in the viral titer compared to the untreated viral strains. Additionally, a 50% reduction in the size of the syncytium was found. These results demonstrate the antiviral potential of HRA2pl in clinical samples, paving the way toward clinical trials.
急性呼吸道感染是一组由病毒、细菌和寄生虫引起的疾病，主要影响 5 岁以下儿童和免疫功能低下的老年人。在墨西哥，这些感染是儿童发病的主要原因，2019 年卫生部报告了超过 2600 万例呼吸道感染病例。人类呼吸道合胞病毒（hRSV）、人类偏肺病毒（hMPV）和人类副流感病毒-2（hPIV-2）是许多呼吸道感染的罪魁祸首。目前，针对融合蛋白 F 的单克隆抗体帕利珠单抗是 hRSV 感染的治疗选择。该蛋白正在研究设计抗病毒肽，通过抑制病毒和宿主细胞的融合来发挥作用。因此，我们研究了 HRA2pl 肽的抗病毒活性，该肽与 hMPV 的 F 蛋白的七肽重复 A 结构域竞争。该重组肽使用病毒瞬时表达系统获得。融合肽的作用通过 进入试验进行评估。此外，通过评估病毒滴度和合胞体大小，研究了 HRA2pl 在从 hRSV、hMPV 或 hPIV-2 感染患者获得的临床样本中的病毒分离物中的有效性。HRA2pl 肽影响病毒的进入能力，与未经处理的病毒株相比，病毒滴度降低了 4 个对数级。此外，还发现合胞体的大小减少了 50%。这些结果表明 HRA2pl 在临床样本中具有抗病毒潜力，为临床试验铺平了道路。
