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      Therapeutic Application of Alpha-1 Antitrypsin in COVID-19

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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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            Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

            There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).
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              The species Severe acute respiratory syndrome-related coronavirus : classifying 2019-nCoV and naming it SARS-CoV-2

              The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
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                Author and article information

                Journal
                Am J Respir Crit Care Med
                Am J Respir Crit Care Med
                ajrccm
                American Journal of Respiratory and Critical Care Medicine
                American Thoracic Society
                1073-449X
                1535-4970
                30 March 2021
                July 2021
                30 March 2021
                : 204
                : 2
                : 224-227
                Affiliations
                [ 1 ]Saarland University

                Homburg, Germany
                [ 2 ]German Primate Center–Leibniz Institute for Primate Research

                Göttingen, Germany
                [ 3 ]University of Göttingen

                Göttingen, Germany
                [ 4 ]Tongji University

                Shanghai, China
                [ 5 ]Hannover Medical School

                Hannover, Germany
                [ 6 ]Saarland University Medical Center

                Homburg, Germany
                [ 7 ]Kamada Ltd.

                Rehovot, Israel
                Author notes
                [ ]Corresponding author (e-mail: robert.bals@ 123456uks.eu ).
                [*]

                These authors contributed equally to this work.

                Other members of the AAT-in-COVID-19 Study Group: Yiwen Yao, Saarland University, Homburg, Germany; Nastasja Seiwert, Hannover Medical School, Hannover, Germany; and Guy Danziger, Saarland University, Homburg, Germany.

                Author information
                https://orcid.org/0000-0002-4460-0337
                Article
                202104-0833LE
                10.1164/rccm.202104-0833LE
                8650782
                33961754
                b78b6b91-e0bf-4866-a8f8-3e83e0d190c4
                Copyright © 2021 by the American Thoracic Society

                This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 ( https://creativecommons.org/licenses/by-nc-nd/4.0/). For commercial usage and reprints, please contact Diane Gern ( dgern@ 123456thoracic.org ).

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