A SARS-CoV-2 antiviral therapy score card.
A SARS-CoV-2 antiviral therapy score card.
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DOI：
10.35772/ghm.2020.01082
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发表时间：
2020-09
期刊：
影响因子：
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通讯作者：
R. Shafer
中科院分区：
文献类型：
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作者：
R. Shafer
新冠大流行引发了一场前所未有的行动，旨在为感染新冠病毒（SARS-CoV - 2）的患者确定有效的治疗方法。截至2020年9月，在ClinicalTrials.gov或世界卫生组织国际临床试验平台网站上已注册了750多项已完成、正在进行或计划进行的旨在抑制新冠病毒复制的药物临床试验。这些试验中研究的大多数治疗方法是重新利用已获许可或处于研究阶段的药物，它们针对病毒复制所需的病毒蛋白或细胞通路。使用重新利用的化合物是可以理解的，因为除了单克隆抗体外，新型新冠病毒特异性药物还需要数月才能用于人体试验。这篇社论介绍了我认为应优先进行临床测试的那些化合物：i）病毒RNA聚合酶抑制剂，包括GS - 441524、其前药瑞德西韦以及EIDD - 2801；ii）进入抑制剂，包括单克隆抗体、ACE2分子诱饵和肽融合抑制剂；iii）干扰素β和λ的注射用和吸入用制剂；iv）宿主跨膜蛋白酶丝氨酸2（TMPRSS2）抑制剂、内体运输抑制剂和嘧啶合成抑制剂。由于新冠病毒大流行，并且其最严重的后果是由对感染的免疫反应失调导致的，理想的治疗方法应该价格低廉，并且能够在患者最初确诊时用于非住院患者。
The COVID-19 pandemic has unleashed an unprecedented effort to identify efficacious treatments for persons infected with SARS-CoV-2. As of September 2020, more than 750 completed, ongoing, or planned clinical trials of drugs intended to inhibit SARS-CoV-2 replication have been registered on the ClinicalTrials.gov or WHO International Clinical Trials Platform websites. Most of the treatments studied in these trials are repurposed licensed or investigational drugs targeting viral proteins or cellular pathways required for virus replication. The use of repurposed compounds is understandable because with the exception of monoclonal antibodies, it will be several months before novel SARS-CoV-2-specific drugs will be available for human testing. This editorial describes those compounds that I believe should be prioritized for clinical testing: i) viral RNA polymerase inhibitors including GS-441524, its prodrug remdesivir, and EIDD-2801; ii) entry inhibitors including monoclonal antibodies, ACE2 molecular decoys, and peptide fusion inhibitors; iii) parenteral and inhalational preparations of interferon β and λ; and iv) inhibitors of host transmembrane protease serine 2 (TMPRSS2), endosomal trafficking, and pyrimidine synthesis. As SARS-CoV-2 is pandemic and as its most severe consequences result from a dysregulated immunological response to infection, the ideal therapies should be inexpensive and should be able to be administered to non-hospitalized persons at the time of their initial diagnosis.