Nucleosides for the treatment of respiratory RNA virus infections.

Q2 Pharmacology, Toxicology and Pharmaceutics Antiviral Chemistry and Chemotherapy Pub Date : 2018-01-01 DOI:10.1177/2040206618764483
Paul C Jordan, Sarah K Stevens, Jerome Deval
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Abstract

Influenza virus, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, and rhinoviruses are among the most common viruses causing mild seasonal colds. These RNA viruses can also cause lower respiratory tract infections leading to bronchiolitis and pneumonia. Young children, the elderly, and patients with compromised cardiac, pulmonary, or immune systems are at greatest risk for serious disease associated with these RNA virus respiratory infections. In addition, swine and avian influenza viruses, together with severe acute respiratory syndrome-associated and Middle Eastern respiratory syndrome coronaviruses, represent significant pandemic threats to the general population. In this review, we describe the current medical need resulting from respiratory infections caused by RNA viruses, which justifies drug discovery efforts to identify new therapeutic agents. The RNA polymerase of respiratory viruses represents an attractive target for nucleoside and nucleotide analogs acting as inhibitors of RNA chain synthesis. Here, we present the molecular, biochemical, and structural fundamentals of the polymerase of the four major families of RNA respiratory viruses: Orthomyxoviridae, Pneumoviridae/Paramyxoviridae, Coronaviridae, and Picornaviridae. We summarize past and current efforts to develop nucleoside and nucleotide analogs as antiviral agents against respiratory virus infections. This includes molecules with very broad antiviral spectrum such as ribavirin and T-705 (favipiravir), and others targeting more specifically one or a few virus families. Recent advances in our understanding of the structure(s) and function(s) of respiratory virus polymerases will likely support the discovery and development of novel nucleoside analogs.

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治疗呼吸道 RNA 病毒感染的核苷类药物。
流感病毒、呼吸道合胞病毒、人类偏肺病毒、副流感病毒、冠状病毒和鼻病毒是引起轻微季节性感冒的最常见病毒。这些 RNA 病毒还可引起下呼吸道感染,导致支气管炎和肺炎。幼儿、老人和心脏、肺部或免疫系统受损的病人最有可能患上与这些 RNA 病毒呼吸道感染相关的严重疾病。此外,猪流感病毒和禽流感病毒,以及与严重急性呼吸系统综合征相关的冠状病毒和中东呼吸系统综合征冠状病毒也对普通人群构成了重大的流行威胁。在这篇综述中,我们描述了目前由 RNA 病毒引起的呼吸道感染所导致的医疗需求,这也证明了为确定新的治疗药物而进行的药物研发工作是正确的。呼吸道病毒的 RNA 聚合酶是核苷和核苷酸类似物作为 RNA 链合成抑制剂的一个有吸引力的靶点。在此,我们介绍了 RNA 呼吸道病毒四大家族聚合酶的分子、生化和结构基础:正粘病毒科、肺炎病毒科/副粘病毒科、冠状病毒科和皮卡病毒科。我们总结了过去和现在为开发核苷和核苷酸类似物作为抗呼吸道病毒感染的抗病毒药物所做的努力。其中包括抗病毒谱非常广的分子,如利巴韦林和 T-705(法非拉韦),以及其他更专门针对一个或几个病毒科的分子。最近,我们对呼吸道病毒聚合酶的结构和功能的了解取得了进展,这将有助于发现和开发新型核苷类似物。
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来源期刊
Antiviral Chemistry and Chemotherapy
Antiviral Chemistry and Chemotherapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
5.20
自引率
0.00%
发文量
5
审稿时长
15 weeks
期刊介绍: Antiviral Chemistry & Chemotherapy publishes the results of original research concerned with the biochemistry, mode of action, chemistry, pharmacology and virology of antiviral compounds. Manuscripts dealing with molecular biology, animal models and vaccines are welcome. The journal also publishes reviews, pointers, short communications and correspondence.
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