Prospects for the Development of Anti-Influenza Drugs Based on Medicinal Mushrooms (Review)
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pects for the Development of Anti-Influenza Drugs Based on Medicinal Mushrooms (Review) T. V. Teplyakovaa, *, T. N. Ilyichevaa, b, and N. A. Markovicha, ** a
State Research Center of Virology and Biotechnology “Vector”, Koltsovo, Novosibirsk oblast, 630559 Russia bNovosibirsk State University, Novosibirsk, 630090 Russia *e-mail: [email protected] **e-mail: [email protected] Received December 12, 2019; revised April 15, 2020; accepted April 22, 2020
Abstract—Russian and international publications on the antiviral activity of medicinal mushrooms against influenza, which have been studied in cell culture and animal models, on the presence of sialidase (neuraminidase) inhibitors and RNA polymerase inhibitors of influenza virus are considered. The activity against influenza of both aqueous extracts of higher fungi and the polysaccharides, peptidoglycans, proteins, melanin, polyphenols, and terpenoids present in them is described. It is noted that further studies of the antiviral mechanisms of these components of medicinal mushrooms, both those grown in natural conditions and those cultivated with solid-phase or submerged methods in laboratory and factory conditions, are required in order to develop drugs based on them. Keywords: medicinal mushrooms, Basidiomycota, influenza virus, neuraminidase, sialidase, RNA polymerase, inhibition, polysaccharides, melanin, terpenoids, polyphenols, cultivation DOI: 10.1134/S0003683820050142
INTRODUCTION The most effective approaches to the prevention and control of influenza are vaccination and antiviral therapy. Currently, influenza can be effectively treated with antiviral drugs, the action of which targets influenza virus (IV) proteins or an increase in the body’s defenses [1]. During the influenza season of 2018–2019 in the United States, three viral neuraminidase (NA) inhibitors were recommended for use against IV types A and B: oral oseltamivir phosphate (Tamiflu®), aerosol zanamivir (Relenza®), and intravenous peramivir (Rapivab®). The fourth drug, oral baloxavir (Xofluza®), is a cap-dependent endonuclease inhibitor that interferes with the transcription of viral RNA and blocks viral replication (https://www.cdc.gov/flu/ professionals/antivirals/summary-clinicians.htm). In Russia, arbidol in addition to NA inhibitors, gained widespread use. Since resistance to the existing anti-influenza drugs is increasing, it becomes necessary to search for new inhibitors that affect other proteins and enzymes present in IV. In this regard, new antiviral strategies that target hemagglutinin [2], RNA polymerase [3–5], NA [6, 7], nucleoprotein [8], and nonstructural protein 1 [9, 10] are considered. Anti-influenza agents that regulate cellular metabolism, as well as the signaling pathways and antiviral response of the host, are
also promising [11]. However, the use of the M2 ion channel inhibitors, amantadine and rimantadine, is not recommended, since type A IV is resistant to them, and they do not affect type B IV [12]. The development of antiviral drugs significantly lags behind the d
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