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      Kakkonto, shosaikoto, Platycodon grandiflorum root, and gypsum (a Japanese original combination drug known as saikatsugekito): Pharmacological review of its activity against viral infections and respiratory inflammatory conditions and a discussion of its applications to COVID‐19

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          ABSTRACT

          Aim

          Traditional Japanese (Kampo) medicine has been used to treat viral infectious diseases. In particular, saikatsugekito (a combination drug of kakkonto, shosaikoto, Platicodon glandiflorum root, and gypsum) has been reported to be useful during the past influenza pandemic. The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has spread worldwide, causing the novel coronavirus disease (COVID‐19) to emerge as a pandemic. In this article, we conducted a literature review on the pharmacological activities of the components present in saikatsugekito against viral infection and respiratory inflammation.

          Methods

          We searched PubMed and the Cochrane Library for English articles, as well as Ichushi and J‐stage for Japanese articles. Articles published until January 1, 2000 were retrieved using the keywords ‘kakkonto’, ‘shosaikoto’, ‘Platycodon’, and ‘gypsum’. We then extracted articles on basic research investigating viral infections, inflammation, cytokine, the immune response, and lung tissue damage.

          Results

          We extracted 28 eligible articles. Kampo medicines have antiviral activities by interfering with the attachment, internalization, replication, progeny virion release, and cell‐to‐cell spreading of single‐strand RNA viruses. They also enhance the immunomodulating activities of the host, including cytokine production, regulation of multiple immune cells, and protection from lung tissue injury. Furthermore, Kampo medicine has been found to regulate body temperature and airway mucin release.

          Conclusion

          The results demonstrated that Kampo medicine has therapeutic activities against single‐strand RNA virus infections and respiratory inflammation, and may also have activities against SARS‐CoV‐2. Further research is required to investigate the activity of Kampo medicines, such as saikatsugekito, against SARS‐CoV‐2.

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          Most cited references92

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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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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                Author and article information

                Contributors
                takayama@med.tohoku.ac.jp
                Journal
                10.1002/(ISSN)2053-4515
                TKM2
                Traditional & Kampo Medicine
                Wiley Publishing Asia Pty Ltd (Melbourne )
                2053-4515
                11 October 2020
                Affiliations
                [ 1 ] Department of Kampo Medicine Tohoku University Hospital Sendai Japan
                [ 2 ] Department of Education and Support for Regional Medicine Tohoku University Hospital Sendai Japan
                [ 3 ] Department of Kampo and Integrative Medicine Tohoku University Graduate School of Medicine Sendai Japan
                [ 4 ] Department of Japanese‐Oriental (Kampo) Medicine Graduate School of Medicine, Chiba University Chiba Japan
                [ 5 ] Akashi Clinic Tokyo Japan
                Author notes
                [*] [* ] Correspondence. Shin Takayama

                Tel: +81 22 717 7587

                Fax: +81 22 717 7508

                Email: takayama@ 123456med.tohoku.ac.jp

                Article
                TKM21258
                10.1002/tkm2.1258
                7675610
                0ed5e5da-e501-47bc-99f1-27418a782ecb
                © 2020 The Authors. Traditional & Kampo Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Oriental Medicine and Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 2, Tables: 2, Pages: 13, Words: 9098
                Product
                Funding
                Funded by: Joint Research Project of Kampo medicine for COVID‐19
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.4 mode:remove_FC converted:19.11.2020

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