Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells

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 role smoking in SARS-CoV-2 infection. Here, we show cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger protein catabolism. BaP induces aryl hydrocarbon receptor (AhR)-dependent upregulation ubiquitin E3 ligase Skp2 ubiquitination. lung tissues non-smokers higher than smokers, consistent with findings tobacco carcinogens downregulate mice. Tobacco inhibit spike pseudovirions infection cells. Given accounts 8 million deaths including 2.1 cancer annually oncoprotein, use should not be recommended cessation plan prepared pandemic.