Suppression of SARS-CoV-2 Infection by Existing Kampo Formulas and Crude Constituent Drugs Used for Treatment of Common Cold Respiratory Symptoms

Overview

Journal Front Pharmacol

Date 2022 Apr 15

PMID 35422704

Authors

Masaki Kakimoto

Toshihito Nomura

Tanuza Nazmul

Hiroki Kitagawa

Keishi Kanno

Keiko Ogawa-Ochiai

Hiroki Ohge

Masanori Ito

Takemasa Sakaguchi

Affiliations

Soon will be listed here.

Abstract

Several traditional Japanese Kampo formulas are known to have inhibitory effects on infections with viruses that cause respiratory symptoms. Although some herbs and their components have been reported to suppress SARS-CoV-2 replication , it is difficult to compare effective Kampo formulas because of the different methods used in studies. Thus, we carried out experiments on the suppression of SARS-CoV-2 infection by Kampo formulas and crude drugs used for the common cold to compare their suppressive effects on virus infection. After infecting VeroE6/TMPRSS2 cells with SARS-CoV-2, lysates of the Kampo formulas and crude drugs were added, and after 24 h, the infectious titer in the medium was measured by the TCID method. Maoto was the most effective among the Kampo formulas, and Ephedrae herba was the most effective among the constituent crude drugs. However, a comparison of the suppressive effects of Ephedrae herba and Kampo formulas containing Ephedrae herba showed that the suppressive effect on virus infection did not depend on the content of Ephedrae herba. Based on the results, we believe that the use of Maoto among Kampo formulas is suitable as a countermeasure against COVID-19.

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References

Yamamotoya T, Nakatsu Y, Kanna M, Hasei S, Ohata Y, Encinas J . Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target. Sci Rep. 2021; 11(1):18581. PMC: 8448864. DOI: 10.1038/s41598-021-97972-3. View

Ho J, Chang H, Lin C, Liu C, Hsieh C, Horng J . Characterization of the anti-influenza activity of the Chinese herbal plant Paeonia lactiflora. Viruses. 2014; 6(4):1861-75. PMC: 4014724. DOI: 10.3390/v6041861. View

Kubo T, Nishimura H . Antipyretic effect of Mao-to, a Japanese herbal medicine, for treatment of type A influenza infection in children. Phytomedicine. 2006; 14(2-3):96-101. DOI: 10.1016/j.phymed.2006.09.015. View

Hsu J . Covid-19: What now for remdesivir?. BMJ. 2020; 371:m4457. DOI: 10.1136/bmj.m4457. View

Su H, Yao S, Zhao W, Li M, Liu J, Shang W . Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients. Acta Pharmacol Sin. 2020; 41(9):1167-1177. PMC: 7393338. DOI: 10.1038/s41401-020-0483-6. View

Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I . Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A. 2020; 117(13):7001-7003. PMC: 7132130. DOI: 10.1073/pnas.2002589117. View

Hu K, Guan W, Bi Y, Zhang W, Li L, Zhang B . Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: A multicenter, prospective, randomized controlled trial. Phytomedicine. 2021; 85:153242. PMC: 7229744. DOI: 10.1016/j.phymed.2020.153242. View

Nomura T, Fukushi M, Oda K, Higashiura A, Irie T, Sakaguchi T . Effects of Traditional Kampo Drugs and Their Constituent Crude Drugs on Influenza Virus Replication : Suppression of Viral Protein Synthesis by Glycyrrhizae Radix. Evid Based Complement Alternat Med. 2019; 2019:3230906. PMC: 6913311. DOI: 10.1155/2019/3230906. View

Nagai T, Kataoka E, Aoki Y, Hokari R, Kiyohara H, Yamada H . Alleviative Effects of a Kampo (a Japanese Herbal) Medicine "Maoto (Ma-Huang-Tang)" on the Early Phase of Influenza Virus Infection and Its Possible Mode of Action. Evid Based Complement Alternat Med. 2014; 2014:187036. PMC: 3978902. DOI: 10.1155/2014/187036. View

10.

Dobson J, Whitley R, Pocock S, Monto A . Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015; 385(9979):1729-1737. DOI: 10.1016/S0140-6736(14)62449-1. View

11.

Muthuri S, Venkatesan S, Myles P, Leonardi-Bee J, Al Khuwaitir T, Al Mamun A . Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med. 2014; 2(5):395-404. PMC: 6637757. DOI: 10.1016/S2213-2600(14)70041-4. View

12.

Ueda K, Kawabata R, Irie T, Nakai Y, Tohya Y, Sakaguchi T . Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses. PLoS One. 2013; 8(1):e55343. PMC: 3555825. DOI: 10.1371/journal.pone.0055343. View

13.

Odaguchi H, Hyuga S, Sekine M, Nakamori S, Takemoto H, Huang X . [The Adverse Effects of Ephedra Herb and the Safety of Ephedrine Alkaloids-free Ephedra Herb Extract (EFE)]. Yakugaku Zasshi. 2019; 139(11):1417-1425. DOI: 10.1248/yakushi.19-00122. View

14.

Hou S, Xu X, Wang Y, Yang Y . Ephedrannin B exerts anti-viral and anti-inflammatory properties in BEAS-2B cells infected with respiratory syncytial virus. J Biosci. 2020; 45. View

15.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M . Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30(3):269-271. PMC: 7054408. DOI: 10.1038/s41422-020-0282-0. View

16.

Shirayama R, Shoji M, Sriwilaijaroen N, Hiramatsu H, Suzuki Y, Kuzuhara T . Inhibition of PA endonuclease activity of influenza virus RNA polymerase by Kampo medicines. Drug Discov Ther. 2016; 10(2):109-13. DOI: 10.5582/ddt.2016.01010. View

17.

van de Sand L, Bormann M, Alt M, Schipper L, Silke Heilingloh C, Steinmann E . Glycyrrhizin Effectively Inhibits SARS-CoV-2 Replication by Inhibiting the Viral Main Protease. Viruses. 2021; 13(4). PMC: 8066091. DOI: 10.3390/v13040609. View

18.

Motoo Y, Arai I, Tsutani K . Use of Kampo diagnosis in randomized controlled trials of Kampo products in Japan: a systematic review. PLoS One. 2014; 9(8):e104422. PMC: 4132104. DOI: 10.1371/journal.pone.0104422. View

19.

Ma J, Huo X, Chen X, Zhu W, Yao M, Qiao Y . [Study on screening potential traditional Chinese medicines against 2019-nCoV based on Mpro and PLP]. Zhongguo Zhong Yao Za Zhi. 2020; 45(6):1219-1224. DOI: 10.19540/j.cnki.cjcmm.20200216.401. View

20.

Mantani N, Andoh T, Kawamata H, Terasawa K, Ochiai H . Inhibitory effect of Ephedrae herba, an oriental traditional medicine, on the growth of influenza A/PR/8 virus in MDCK cells. Antiviral Res. 2000; 44(3):193-200. DOI: 10.1016/s0166-3542(99)00067-4. View