Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russian Federation.
Curr Med Chem. 2021;28(26):5284-5310. doi: 10.2174/0929867328666210208181724.
Coronaviruses (CoVs) belong to a large family of zoonotic supercapsid viruses, including about 40 species of RNA-containing viruses with several strains capable of causing damage to the lungs and respiratory tract. The severe acute respiratory syndrome coronavirus (SARS-CoV) was responsible for the worldwide SARS outbreak in 2003. The rapid global spread of SARS-CoV-2 has been the cause of significant health concerns and thousands of deaths in 2019-2020 and outlined the need for novel antivirals. The present review is devoted to the development of effective and selective nucleoside drugs for the treatment of coronavirus infections. To date, about half of antivirals have been created based on nucleosides. The majority of drugs based on nucleosides have been approved by FDA. This indicates a fruitful area for the development of novel antivirals based on nucleosides. The review describes the main features of pathogenic SARS-CoV, MERS-CoV, and SARS-CoV-2 strains, presents their comparison, considers promising approaches to creating nucleoside drugs for the treatment of coronavirus infections and provides a systematic evaluation of all the known nucleoside derivatives, which inhibit the reproduction of coronaviruses in cells. To date, two known nucleoside drugs (Remdesivir, Favipiravir) have been recommended for the treatment of SARS-CoV-2 infection and nine hit compounds based on nucleosides and their analogues have been found, one of which efficiently suppressing SARS-CoV-2 replication and eight others inhibiting SARS-CoV replication.
冠状病毒(CoV)属于大型的动物源性超级衣壳病毒家族,其中包括约 40 种含 RNA 的病毒,有几种毒株能够损害肺部和呼吸道。严重急性呼吸综合征冠状病毒(SARS-CoV)是 2003 年全球严重急性呼吸综合征(SARS)爆发的罪魁祸首。SARS-CoV-2 在全球的迅速传播引起了人们对健康的极大关注,并在 2019-2020 年导致了数千人死亡,这突显了开发新型抗病毒药物的必要性。本综述致力于开发针对冠状病毒感染的有效和选择性核苷类药物。迄今为止,约有一半的抗病毒药物是基于核苷开发的。大多数基于核苷的药物已获得 FDA 批准。这表明基于核苷开发新型抗病毒药物是一个很有前景的领域。该综述描述了致病性 SARS-CoV、MERS-CoV 和 SARS-CoV-2 毒株的主要特征,对它们进行了比较,考虑了开发用于治疗冠状病毒感染的核苷类药物的有前途的方法,并对所有已知的抑制冠状病毒在细胞中复制的核苷衍生物进行了系统评价。迄今为止,已有两种已知的核苷类药物(瑞德西韦、法匹拉韦)被推荐用于治疗 SARS-CoV-2 感染,已经发现了九种基于核苷及其类似物的有效化合物,其中一种能够有效抑制 SARS-CoV-2 的复制,另外八种能够抑制 SARS-CoV 的复制。