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      More evidence is urgently needed to confirm the relation between angiotensin-converting enzyme inhibitors and COVID-19

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      Journal of Molecular and Cellular Cardiology
      Elsevier Ltd.

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          Abstract

          Dear Editor, The Corona Virus Disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been announced as a pandemic by the World Health Organization (WHO). As of March 25, 2020, there are 81,896 confirmed cases of COVID-19 in China and additional 293,602 cases in 195 other countries, areas or territories. The SARS-CoV-2 infection requires binding to the receptors expressed in human tissues. Several studies have demonstrated that SARS-CoV-2 invades host cells through acting with angiotensin-converting enzyme 2 (ACE2). Zhou et al confirmed that SARS-CoV-2 interacts with same cell entry receptor, ACE2, as the SARS-CoV [1]. Vincent Munster et al established a method to quickly screen the receptor-binding domain of SARS-CoV-2, and further proved ACE2 as the receptor for SARS-CoV-2 infection [2]. Another recent study also showed that similar to SARS-CoV, SARS-CoV-2 employs ACE2 as the entry receptor depending on serine protease TMPRSS2 [3]. Now, the structure of dimeric full-length human ACE2 as well as the interaction site between CoV spike (S) glycoprotein of SARS-CoV-2 and ACE2 has been indentified. The affinity of S protein to ACE2 is 10 to 20 times higher than that of SARS-CoV [4,5]. All these findings suggested that ACE2 may serve as the “gate” from where SARS-CoV-2 initially enters the infect host cells. As an isoenzyme of ACE, ACE2 reduces angiotensin II level, and promotes generation of angiotensin 1–7 (Ang1–7) to exert several protective effects such as vasodilation, anti-inflammation, anti-proliferation and anti-fibrosis [6]. ACE2 is mainly expressed in the lung, testis, kidney, cardiovascular and gastrointestinal system. A recent study showed that ACE2 expression is enriched in a small population of type II alveolar cells according to the public database and the state-of-the-art single-cell RNA-Seq technique [7]. It suggests that alveolar cells may be the target cell of coronavirus infection to cause serious pneumonia. It is noted that some patients with COVID-19 also suffer form hypertension. Angiotensin-converting enzyme inhibitors (ACEI), as one of the most common antihypertensive drugs, are widely used in clinic. There is a speculation that long-term ACEI administration might increase ACE2 level due to the feedback mechanisms. Elevated expression of ACE2 can potentially enhance the binding of SARS-CoV-2 to S protein, accelerate coronavirus replication, and aggravate the symptoms of pneumonia. However, the recommendation to discontinue the use of ACEI in COVID-19 patients is not well grounded due to the lack of evidence in clinical settings. From our own prospective, more evidence is urgently needed to further support this. First, data is required to indicate that long-term ACEI administration can increase the level of ACE2. The difference of ACE2 level and activity in normotensive individuals and hypertensive individuals with or without long-term ACEI treatment should be analyzed. It is better to do autopsy to look into the ACE2 expression in the lung tissues of patients who died of COVID-19 with or without a medication history of ACEI, which can provide a first-hand evidence to confirm the relation between ACEI treatment and ACE2 expression. Second, the hypothesis that ACEI promotes SARS-CoV-2 infection should be further verified, using hypertensive animals with ACEI administration for a long time or with ACE2 over-expression, such as hACE2 transgenic mice or ACE2 conditional knock-in mice to see whether they become more susceptible to SARS-CoV-2 infection or more likely to have severe symptoms, excessive virus copies and aggravated pulmonary injury. On the other hand, such susceptibility may be attenuated in ACE2 knock-out animals. More importantly, clinical evidence is indispensable. A retrospective multi-center cohort study regarding COVID-19 patients with hypertension is desired. It is to be elucidated whether long-term ACEI administration is a risk factor for the development to severe or critical COVID-19. It is noteworthy that several cases relapse after the COVID-19 patients have been cured in clinic, which suggests that the coronaviruses may still be latent in the body. Thus, discharged patients should also be regularly followed up to determine whether there is a statistical difference on recurrence rate with or without long-term ACEI treatment. In summary, more evidence is urgently needed to confirm the relation between ACEI and COVID-19, which could guide the clinical applications of anti-hypertension medication in COVID-19 patients.

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            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.
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              Is Open Access

              Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

              Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260
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                Author and article information

                Contributors
                Journal
                J Mol Cell Cardiol
                J. Mol. Cell. Cardiol
                Journal of Molecular and Cellular Cardiology
                Elsevier Ltd.
                0022-2828
                1095-8584
                6 April 2020
                6 April 2020
                Affiliations
                [a ]Nantong University, Nantong, China
                [b ]Affiliated Hospital of Nantong University, Nantong, China
                Author notes
                [* ]Correspsonding author at: Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China. mengguoliang@ 123456ntu.edu.cn
                Article
                S0022-2828(20)30087-0
                10.1016/j.yjmcc.2020.04.003
                7195166
                32272142
                34c3d1f5-6c45-487c-bb49-b8d8f61664ce
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 12 March 2020
                : 25 March 2020
                Categories
                Article

                Cardiovascular Medicine
                Cardiovascular Medicine

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