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      New perspectives on natural flavonoids on COVID‐19‐induced lung injuries

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          Abstract

          The SARS‐CoV‐2 virus, responsible for COVID‐19, spread rapidly worldwide and became a pandemic in 2020. In some patients, the virus remains in the respiratory tract, causing pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), and sepsis, leading to death. Natural flavonoids (aglycone and glycosides) possess broad biological activities encompassing antiinflammatory, antiviral, antitumoral, antiallergic, antiplatelet, and antioxidant effects. While many studies have focused on the effects of natural flavonoids in experimental models, reports based on clinical trials are still insufficient. In this review, we highlight the effects of flavonoids in controlling pulmonary diseases, particularly the acute respiratory distress syndrome, a consequence of COVID‐19, and their potential use in coronavirus‐related diseases. Furthermore, we also focus on establishing a relationship between biological potential and chemical aspects of related flavonoids and discuss several possible mechanisms of action, pointing out some possible effects on COVID‐19.

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          Most cited references116

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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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              Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

              A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
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                Author and article information

                Contributors
                carla.prado@unifesp.br
                joao.lago@ufabc.edu.br
                Journal
                Phytother Res
                Phytother Res
                10.1002/(ISSN)1099-1573
                PTR
                Phytotherapy Research
                John Wiley & Sons, Ltd. (Chichester, UK )
                0951-418X
                1099-1573
                29 April 2021
                : 10.1002/ptr.7131
                Affiliations
                [ 1 ] Department of Bioscience Federal University of São Paulo Santos São Paulo Brazil
                [ 2 ] Department of Immunology, Institute of Biomedical Sciences University of São Paulo São Paulo São Paulo Brazil
                [ 3 ] Center of Natural Sciences and Humanities Federal University of ABC São Paulo São Paulo Brazil
                [ 4 ] Department of Physiological Sciences Santa Casa de São Paulo School of Medical Sciences São Paulo São Paulo Brazil
                [ 5 ] Department of Biological Science Federal University of São Paulo Diadema São Paulo Brazil
                Author notes
                [*] [* ] Correspondence

                João Henrique Ghilardi Lago, Center of Natural Sciences and Humanities, Federal University of ABC, São Paulo, São Paulo, Brazil.

                Email: joao.lago@ 123456ufabc.edu.br

                Carla Maximo Prado, Department of Bioscience, Federal University of São Paulo, Santos, São Paulo, Brazil.

                Email: carla.prado@ 123456unifesp.br

                Author information
                https://orcid.org/0000-0002-1193-8374
                Article
                PTR7131
                10.1002/ptr.7131
                8242604
                33928690
                63f3cf4e-a5b6-471f-80a8-ca71a325da54
                © 2021 John Wiley & Sons Ltd.

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 11 March 2021
                : 20 January 2021
                : 06 April 2021
                Page count
                Figures: 3, Tables: 3, Pages: 19, Words: 14068
                Funding
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico , open-funder-registry 10.13039/501100003593;
                Award ID: 301354/2019‐7
                Award ID: 306278/2015‐4
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior , open-funder-registry 10.13039/501100002322;
                Award ID: financial code 001
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo , open-funder-registry 10.13039/501100001807;
                Award ID: 2018/06088‐0
                Award ID: 2018/07885‐1
                Award ID: 2020/01221‐4
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:30.06.2021

                Pharmacology & Pharmaceutical medicine
                ace2,acute lung injury,covid‐19,flavonoids,sars‐cov‐2
                Pharmacology & Pharmaceutical medicine
                ace2, acute lung injury, covid‐19, flavonoids, sars‐cov‐2

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