Inhibition of PA endonuclease activity of influenza virus RNA polymerase by Kampo medicines

Shirayama, Riku; Shoji, Masaki; Sriwilaijaroen, Nongluk; Hiramatsu, Hiroaki; Suzuki, Yasuo; Kuzuhara, Takashi

doi:10.5582/ddt.2016.01010

Cited by 17 publications

(15 citation statements)

References 17 publications

(19 reference statements)

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“…Inhibitory activity against HRSV attachment was observed when human host cells were treated with hot water extracts of fresh ginger, which is contained in 'classical' KKT, whereas dried ginger did not have the inhibitory activity [21]. Shirayama et al reported that KKT, SST, and other Kampo formulas frequently used for the common cold had dose-dependent inhibitory activity against the polymerase acidic protein endonuclease, which is essential for the acquisition of primers for viral mRNA transcription [22].…”

Section: Kakkonto (Kkt)mentioning

confidence: 99%

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

Arita

Ono

Saito

et al. 2020

Traditional & Kampo Medicine

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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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Section: Kakkonto (Kkt)mentioning

confidence: 99%

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

Arita

Ono

Saito

et al. 2020

Traditional & Kampo Medicine

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“…This is the point of action of baloxavir marboxil, an orally administered and long-acting anti-influenza drug. This activity was inhibited by extracts of kakkonto, shosaikoto, saikokeishito, keishito, maobushisaishinto, and maoto but not by an extract of chkujountanto [22]. Two of these Kampo drugs (kakkonto and maoto) were Kampo drugs tested in the present study, and both were effective.…”

Section: Discussionmentioning

confidence: 61%

“…Polymerase acidic (PA) protein, one of the three polymerases of influenza virus that works for cap snatching and mRNA synthesis, may be the target of Glycyrrhizae radix . Shirayama et al [22] reported that PA endonuclease activity of influenza virus PA protein was inhibited by Kampo drugs in vitro . This is the point of action of baloxavir marboxil, an orally administered and long-acting anti-influenza drug.…”

Section: Discussionmentioning

confidence: 99%

Effects of Traditional Kampo Drugs and Their Constituent Crude Drugs on Influenza Virus Replication In Vitro: Suppression of Viral Protein Synthesis by Glycyrrhizae Radix

Nomura

Fukushi

Oda

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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An influenza virus epidemic is an important issue in public hygiene, and continuous development on an effective drug is required. Kampo medicine is a traditional medicine that is used clinically for treatment of various diseases in Japan and other East Asian countries. We evaluated the effects of the Kampo drugs maoto, kakkonto, senkyuchachosan, jinkokato, and bakumondoto, which are prescribed for treatment of respiratory symptoms including symptoms caused by influenza, on influenza virus replication in cultured cells. Culture media of influenza virus-infected MDCK(+) cells were tested for hemagglutination and infectivity at 24 h after the addition of Kampo drugs at various concentrations, and four of the five Kampo drugs were found to inhibit virus release to the culture media. These drugs inactivated virus infectivity not by acting on virus particles but by acting on virus-infected cells. In addition, when six crude drugs (Atractylodis lanceae rhizome, Citri unshiu pericarpium, Cnidii rhizome, Glycyrrhizae radix, Rehmanniae radix, and Saposhnikoviae radix) that constitute the effective Kampo drugs were examined, the strongest activity was found for Glycyrrhizae radix (IC50 = 0.27 mg/ml), which selectively suppressed viral protein synthesis. Since Glycyrrhizae radix is contained in many Kampo drugs, it may give anti-influenza virus activity to a broad range of Kampo drugs.

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“…Recently, several new reports related to Kampo and Chinese medicines for influenza infection have been focused on the molecular level [15,[24][25][26][27][28]. Known antivirals, such as neuraminidase inhibitors and M2 proton channel inhibitors, exert an antiviral effect by combining with the viral molecules and inhibiting their function.…”

Section: Discussionmentioning

confidence: 99%

“…The cinnamaldehyde derived from Cinnamon Bark, which is included in maoto, was reported to inhibit the growth of influenza virus through the a defect of translation [27]. Several Kampo medicines including maoto have been reported to inhibit the polymerase acidic protein of influenza A virus [24]. We previously reported, in a clinical trial, that maoto had a quick effect on influenza-related symptoms, such as fever, headache, and myalgia/arthralgia [12].…”

Section: Discussionmentioning

confidence: 99%

Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus

Masui

Nabeshima

Ajisaka

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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We previously reported in randomized controlled trials that maoto, a traditional herbal medicine, showed clinical and virological efficacy for seasonal influenza. In this study, a culturing system for influenza was used to test the effect of maoto. A549 cells in the culture were infected with influenza virus A (PR8) and followed after treatment with maoto; the virus titers in the culture supernatant, intracellular viral proteins, and viral RNA were determined. When infected cells were cultured with maoto for 24 hr, the virus titer and protein were significantly reduced compared with medium only. Other subtypes, A/H3N2, H1N1pdm, and B, were also inhibited by maoto. Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase, especially in the first 30 min. Focusing on the entry step of the influenza virus, we found that endosomal pH, regulated by vacuolar-type H+ ATPase (V-ATPase) located in the membrane, was increased when treated with maoto. We also found that uncoating of influenza viruses was also inhibited by maoto, resulting in the increase of the number of virus particles in endosomes. These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm, probably through the inhibition of V-ATPase. The present study provides evidence that supports the clinical use of maoto for the treatment of influenza.

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Inhibition of PA endonuclease activity of influenza virus RNA polymerase by Kampo medicines

Cited by 17 publications

References 17 publications

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

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

Effects of Traditional Kampo Drugs and Their Constituent Crude Drugs on Influenza Virus Replication In Vitro: Suppression of Viral Protein Synthesis by Glycyrrhizae Radix

Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus

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