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TLR 配体作为慢性乙型肝炎和艾滋病病毒感染新型治疗药物的发现和研发的最新进展。

Recent advances in the discovery and development of TLR ligands as novel therapeutics for chronic HBV and HIV infections.

机构信息

a Department of Infectious Disease , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.

b Department of Gastroenterology and Hepatology , University Hospital Essen, University of Duisburg-Essen , Essen , Germany.

出版信息

Expert Opin Drug Discov. 2018 Jul;13(7):661-670. doi: 10.1080/17460441.2018.1473372. Epub 2018 May 17.

DOI:10.1080/17460441.2018.1473372
PMID:29772941
Abstract

Toll-like receptor (TLR) ligands remain as promising antiviral drug candidates for the treatment of chronic viral infections. Basic research on the mechanisms of antiviral activity of TLR ligands in preclinical animal models and clinical testing of drug candidates have been carried out in recent years. Areas covered: This review provides an overview of the preclinical and clinical testing of TLR ligands in two major viral infections: hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Recent results have further demonstrated the potent antiviral activity of various TLR ligands . A TLR7 agonist is in clinical trials for the treatment of chronic HBV infection while a HBV vaccine using a TLR9 ligand as an adjuvant has proven to be superior to conventional HBV vaccines and has been approved for clinical use. Generally, TLR activation may achieve viral control mainly by promoting adaptive immunity to viral proteins. Expert opinion: Recent research in this field indicates that TLR ligands could be developed as clinically effective drugs if the obstacles concerning toxicity and application routes are overcome. TLR-mediated promotion of adaptive immunity is a major issue for future studies and will determine the future development of TLR ligands as drugs for immunomodulation.

摘要

Toll 样受体 (TLR) 配体仍然是治疗慢性病毒感染有前途的抗病毒药物候选物。近年来,已经在临床前动物模型中对 TLR 配体的抗病毒活性机制进行了基础研究,并对候选药物进行了临床测试。

涵盖领域

本综述概述了 TLR 配体在两种主要病毒感染中的临床前和临床测试:乙型肝炎病毒 (HBV) 和人类免疫缺陷病毒 (HIV)。最近的结果进一步证明了各种 TLR 配体具有强大的抗病毒活性。一种 TLR7 激动剂正在进行治疗慢性 HBV 感染的临床试验,而一种使用 TLR9 配体作为佐剂的 HBV 疫苗已被证明优于传统的 HBV 疫苗,并已获准临床使用。一般来说,TLR 激活可能主要通过促进针对病毒蛋白的适应性免疫来实现病毒控制。

专家意见

该领域的最新研究表明,如果克服了毒性和应用途径方面的障碍,TLR 配体可能被开发为临床有效药物。TLR 介导的适应性免疫促进是未来研究的主要问题,将决定 TLR 配体作为免疫调节剂药物的未来发展。

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