The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused substantial morbidity and mortality, and serious social and economic disruptions worldwide. Unvaccinated or incompletely vaccinated older individuals with underlying diseases are especially prone to severe disease. In patients with non-fatal disease, long COVID affecting multiple body systems may persist for months. Unlike SARS-CoV and Middle East respiratory syndrome coronavirus, which have either been mitigated or remained geographically restricted, SARS-CoV-2 has disseminated globally and is likely to continue circulating in humans with possible emergence of new variants that may render vaccines less effective. Thus, safe, effective and readily available COVID-19 therapeutics are urgently needed. In this Review, we summarize the major drug discovery approaches, preclinical antiviral evaluation models, representative virus-targeting and host-targeting therapeutic options, and key therapeutics currently in clinical use for COVID-19. Preparedness against future coronavirus pandemics relies not only on effective vaccines but also on broad-spectrum antivirals targeting conserved viral components or universal host targets, and new therapeutics that can precisely modulate the immune response during infection.

由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的 2019 冠状病毒病 (COVID-19) 大流行已在全球范围内造成大量发病率和死亡率，并造成严重的社会和经济混乱。未接种疫苗或疫苗接种不完全的患有基础疾病的老年人特别容易患上严重疾病。对于患有非致命疾病的患者，影响多个身体系统的长期新冠病毒可能会持续数月。与 SARS-CoV 和中东呼吸综合征冠状病毒不同，SARS-CoV-2 已在全球范围内传播，并且可能会继续在人类中传播，并可能出现新的变体，从而可能降低疫苗的有效性。因此，迫切需要安全、有效且易于获得的 COVID-19 疗法。在这篇综述中，我们总结了主要的药物发现方法、临床前抗病毒评估模型、代表性的病毒靶向和宿主靶向治疗方案以及目前临床上用于 COVID-19 的关键疗法。应对未来冠状病毒大流行的准备不仅依赖于有效的疫苗，还依赖于针对保守病毒成分或通用宿主靶点的广谱抗病毒药物，以及能够精确调节感染期间免疫反应的新疗法。