The coronavirus disease 2019 (COVID-19) that is wreaking havoc on worldwide public health and economies has heightened awareness about the lack of effective antiviral treatments for human coronaviruses (CoVs). Many current antivirals, notably nucleoside analogs (NAs), exert their effect by incorporation into viral genomes and subsequent disruption of viral replication and fidelity. The development of anti-CoV drugs has long been hindered by the capacity of CoVs to proofread and remove mismatched nucleotides during genome replication and transcription. Here, we review the molecular basis of the CoV proofreading complex and evaluate its potential as a drug target. We also consider existing nucleoside analogs and novel genomic techniques as potential anti-CoV therapeutics that could be used individually or in combination to target the proofreading mechanism.

2019 年冠状病毒病 (COVID-19) 正在对全球公共卫生和经济造成严重破坏，这提高了人们对人类冠状病毒 (CoV) 缺乏有效抗病毒治疗的认识。目前许多抗病毒药物，尤其是核苷类似物 (NA)，通过掺入病毒基因组并随后破坏病毒复制和保真度来发挥作用。抗冠状病毒药物的开发长期以来一直受到冠状病毒在基因组复制和转录过程中校对和去除不匹配核苷酸的能力的阻碍。在这里，我们回顾了 CoV 校对复合物的分子基础，并评估其作为药物靶点的潜力。我们还认为现有的核苷类似物和新型基因组技术是潜在的抗冠状病毒疗法，可以单独或组合使用以针对校对机制。