Abstract
An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.
Keywords: ACE2; SARS-CoV-2; Skp2; benzo(a)pyrene; tobacco smoke.
【저자키워드】 SARS-CoV-2, ACE2, Skp2, benzo(a)pyrene, tobacco smoke., 【초록키워드】 Hospitalized, SARS-COV-2 infection, COVID-19 pandemic, Cancer, Infection, Tobacco, smoking, Spike protein, Adults, cells, mice, death, Smokers, Aryl hydrocarbon receptor, ACE2 protein, smoker, observation, ACE2 mRNA, lung tissue, upregulation, E3 ligase, urgent investigation, pseudovirion, determine, induce, downregulate, carcinogen, CSE, inhibit SARS-CoV-2, 【제목키워드】 SARS-CoV-2 receptor, E3 ubiquitin ligase, lung epithelial cell,