Degradation of SARS-CoV-2 receptor ACE2 by tobacco carcinogen-induced Skp2 in lung epithelial cells

Zhou, G.-B.; Wang, G.-Z.; Zhao, Q.; Liang, F.; Zhang, C.; Zhang, H.; Wang, J.; Chen, Z.-Y.; Wu, R.; Yu, H.; Sun, B.-B.; Feng, R.; Xu, K.-F.

doi:10.1101/2020.10.13.337774

bioRxiv · 10.1101/2020.10.13.337774

Degradation of SARS-CoV-2 receptor ACE2 by tobacco carcinogen-induced Skp2 in lung epithelial cells

Zhou, G.-B.·Wang, G.-Z.·Zhao, Q.·Liang, F.·Zhang, C.·Zhang, H.·Wang, J.·Chen, Z.-Y.·Wu, R.·Yu, H.·Sun, B.-B.·Feng, R.·Xu, K.-F.

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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.

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Zhou, G.-B., Wang, G.-Z., Zhao, Q., Liang, F., Zhang, C., Zhang, H., Wang, J., Chen, Z.-Y., Wu, R., Yu, H., Sun, B.-B., Feng, R., Xu, K.-F.. 2020-10-13. Degradation of SARS-CoV-2 receptor ACE2 by tobacco carcinogen-induced Skp2 in lung epithelial cells. https://doi.org/10.1101/2020.10.13.337774

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