KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
Nat Microbiol. 2021 Oct;6(10):1219-1232. doi: 10.1038/s41564-021-00958-0. Epub 2021 Sep 1.
The coronavirus disease 2019 (COVID-19) pandemic has claimed millions of lives and caused a global economic crisis. No effective antiviral drugs are currently available to treat infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The medical need imposed by the pandemic has spurred unprecedented research efforts to study coronavirus biology. Every virus depends on cellular host factors and pathways for successful replication. These proviral host factors represent attractive targets for antiviral therapy as they are genetically more stable than viral targets and may be shared among related viruses. The application of various 'omics' technologies has led to the rapid discovery of proviral host factors that are required for the completion of the SARS-CoV-2 life cycle. In this Review, we summarize insights into the proviral host factors that are required for SARS-CoV-2 infection that were mainly obtained using functional genetic and interactome screens. We discuss cellular processes that are important for the SARS-CoV-2 life cycle, as well as parallels with non-coronaviruses. Finally, we highlight host factors that could be targeted by clinically approved molecules and molecules in clinical trials as potential antiviral therapies for COVID-19.
2019 年冠状病毒病(COVID-19)大流行已经夺走了数百万人的生命,并导致了全球经济危机。目前尚无有效的抗病毒药物可用于治疗严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染。这场大流行带来的医疗需求促使人们以前所未有的努力研究冠状病毒生物学。每种病毒都依赖于细胞宿主因子和途径来成功复制。这些促进病毒复制的宿主因子是抗病毒治疗的有吸引力的靶点,因为它们在遗传上比病毒靶点更稳定,并且可能在相关病毒中共享。各种“组学”技术的应用导致了对 SARS-CoV-2 生命周期所需的促进病毒复制的宿主因子的快速发现。在这篇综述中,我们总结了主要通过功能遗传和互作组筛选获得的 SARS-CoV-2 感染所需的促进病毒复制的宿主因子的研究进展。我们讨论了对 SARS-CoV-2 生命周期很重要的细胞过程,以及与非冠状病毒的平行关系。最后,我们强调了一些宿主因子,这些因子可以作为 COVID-19 的潜在抗病毒治疗药物,被临床批准的分子和临床试验中的分子靶向。