For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
0
views
26
references
 Top references
cited by
14
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      470
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

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

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Electronic Supplementary Material

          Supplementary material is available for this article at 10.1007/s11684-021-0837-6 and is accessible for authorized users.

          Related collections

          Most cited references26

          • Record: found
          • Abstract: found
          • Article: not found

          Clinical Characteristics of Coronavirus Disease 2019 in China

          Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
          Article 0 comments Cited 13570 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)
            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
            Article 0 comments Cited 9648 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

              Xin Zou, Ke Chen, Jiawei Zou … (2020)
              It has been known that, the novel Coronavirus, 2019-nCoV, which is considered similar to SARS-CoV and originated from Wuhan (China), invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit non-respiratory symptoms, such as kidney failure, implying that 2019-nCoV could also invade other organs. To construct a risk map of different human organs, we analyzed the single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems, including the respiratory, cardiovascular, digestive, and urinary systems. Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection. Based on the findings, we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection. This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s11684-020-0754-0 and is accessible for authorized users.
              Article 0 comments Cited 1062 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Guangbiao Zhou: gbzhou@cicams.ac.cn
                Journal
                Journal ID (nlm-ta): Front Med
                Journal ID (iso-abbrev): Front Med
                Title: Frontiers of Medicine
                Publisher: Higher Education Press (Beijing )
                ISSN (Print): 2095-0217
                ISSN (Electronic): 2095-0225
                Publication date (Electronic): 29 January 2021
                Pages: 1-12
                Affiliations
                [1 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, , Chinese Academy of Medical Sciences and Peking Union Medical College, ; Beijing, 100021 China
                [2 ]GRID grid.410726.6, ISNI 0000 0004 1797 8419, State Key Laboratory of Membrane Biology, Institute of Zoology, , Chinese Academy of Sciences & University of Chinese Academy of Sciences, ; Beijing, 100101 China
                [3 ]GRID grid.443573.2, ISNI 0000 0004 1799 2448, Hubei University of Medicine, ; Shiyan, 442000 China
                [4 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Department of Pathology, Peking Union Medical College Hospital, , Chinese Academy of Medical Sciences, ; Beijing, 100730 China
                [5 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, , Chinese Academy of Medical Sciences, ; Beijing, 100730 China
                [6 ]GRID grid.443382.a, ISNI 0000 0004 1804 268X, Guizhou University School of Medicine, ; Guiyang, 550025 China
                [7 ]GRID grid.24695.3c, ISNI 0000 0001 1431 9176, School of Chinese Materia Medica, , Beijing University of Chinese Medicine, ; Beijing, 100029 China
                Article
                Publisher ID: 837
                DOI: 10.1007/s11684-021-0837-6
                PMC ID: 7843238
                PubMed ID: 33511555
                SO-VID: 9e8b2df3-9e88-4c8e-bcad-4efe56e25ea6
                Copyright © © Higher Education Press 2021
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 25 November 2020
                Date accepted : 8 December 2020
                Categories
                Subject: Research Article

                Keywords: sars-cov-2,tobacco smoke,benzo(a)pyrene,ace2,skp2
                Data availability:
                Keywords: sars-cov-2, tobacco smoke, benzo(a)pyrene, ace2, skp2

                Comments

                Comment on this article

                scite_

                Similar content470

                See all similar

                Cited by14

                See all cited by

                Most referenced authors1,586

                See all reference authors