Lu Yongzhong, Cheng Linyue, Liu Jie
Shandong Provincial Key Laboratory of Biochemical Engineering, Qingdao University of Science and Technology, No. 53, Zhengzhou Road, 266042 Qingdao, China.
Int J Pept Res Ther. 2020;26(2):1043-1049. doi: 10.1007/s10989-019-09906-3. Epub 2019 Aug 13.
Rabies is a serious zoonosis caused by rabies virus (RABV) of the genus , and immunotherapy is now the only approved, effective method for post-exposure prophylaxis against rabies in humans, whereas an effective antiviral therapy is still unavailable if the central nervous system is invaded. Phosphoprotein (P) is known to play pivotal roles in the life cycle of RABV, and has been regarded as a prime target for inhibitors of viral replication. This study aimed to carry out intracellular administration of a kind of P-binding peptide for RABV inhibition. A group of reported P-binding peptides were focused on for activity improvement by quantitative structure-activity relationship (QSAR) method, and then were mediated by cell penetrating peptide (CPP) for intracellular activity evaluation. The QSAR models had good performance in reliability and predictability (R ≥ 0.852, Q ≥ 0.601, ≥ 0.595), and the peptide screened by partial least squares (PLS) QSAR model (R = 0.994, Q = 0.937, = 0.981) exhibited even higher antiviral activity when it was delivered into the cells by CPP. Above all, this study provided an effective way for development of peptide drug against RABV.
狂犬病是由 属的狂犬病病毒（RABV）引起的一种严重人畜共患病，免疫疗法是目前唯一被批准的、有效的人类暴露后狂犬病预防方法，而如果中枢神经系统被侵袭，仍然没有有效的抗病毒治疗方法。已知磷蛋白（P）在RABV的生命周期中起关键作用，并被视为病毒复制抑制剂的主要靶点。本研究旨在通过细胞内给予一种P结合肽来抑制RABV。通过定量构效关系（QSAR）方法对一组已报道的P结合肽进行活性优化，然后通过细胞穿透肽（CPP）介导进行细胞内活性评估。QSAR模型在可靠性和可预测性方面表现良好（R≥0.852，Q≥0.601，≥0.595），通过偏最小二乘法（PLS）QSAR模型筛选出的肽（R = 0.994，Q = 0.937，= 0.981）在通过CPP递送至细胞时表现出更高的抗病毒活性。最重要的是，本研究为开发抗RABV肽药物提供了一种有效方法。
