美国加州大学旧金山分校Andreas S. Puschnik、Melanie Ott等研究人员合作，利用遗传筛选鉴定出SARS-CoV-2和普通感冒冠状病毒的宿主因素。相关论文于2020年12月8日在线发表在《细胞》杂志上。
研究人员对被SARS-CoV-2以及两种季节性循环的普通感冒冠状病毒OC43和229E感染的细胞进行了全基因组CRISPR筛选。这种方法确定了不同的病毒进入因子ACE2（对于SARS-CoV-2）、氨肽酶N（对于229E）和糖胺聚糖（对于OC43）。此外，研究人员发现磷脂酰肌醇磷酸酯的生物合成和胆固醇稳态是促进这三种冠状病毒感染的关键宿主途径。相比之下，溶酶体蛋白TMEM106B似乎是SARS-CoV-2感染所特有的。磷脂酰肌醇激酶和胆固醇稳态的药理抑制作用降低了这三种冠状病毒的复制。
这些发现为了解冠状病毒的生命周期以及开发针对宿主的疗法提供了重要见识。
据介绍，冠状病毒科是导致人类疾病的病毒家族，范围从轻度呼吸道感染到可能致命的急性呼吸窘迫综合征。寻找多种冠状病毒共同的宿主因素可以促进抗击目前和未来冠状病毒大流行疗法的发展。
附：英文原文
Title: Genetic screens identify host factors for SARS-CoV-2 and common cold coronaviruses
Author: Ruofan Wang, Camille R. Simoneau, Jessie Kulsuptrakul, Mehdi Bouhaddou, Katherine A. Travisano, Jennifer M. Hayashi, Jared Carlson-Stevermer, James R. Zengel, Christopher M. Richards, Parinaz Fozouni, Jennifer Oki, Lauren Rodriguez, Bastian Joehnk, Keith Walcott, Kevin Holden, Anita Sil, Jan E. Carette, Nevan J. Krogan, Melanie Ott, Andreas S. Puschnik
Issue&Volume: 2020-12-08
Abstract: The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E) and glycosaminoglycans (for OC43). Additionally, we identified phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection. Pharmacological inhibition of phosphatidylinositol kinases and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle and the development of host-directed therapies.
DOI: 10.1016/j.cell.2020.12.004
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31626-3