Antiviral activity of basidial fungus Inonotus obliquus aqueous extract against SARS-CоV-2 virus (Coronaviridae: Betacoronavirus: Sarbecovirus) in vivo in BALB/c mice model
- Authors: Shipovalov A.V.1, Kudrov G.A.1, Kartashov M.Y.1, Drachkova I.A.1, Pyankov O.V.1, Omigov V.V.1, Taranov O.S.1, Teplyakova T.V.1
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Affiliations:
- State Research Center of Virology and Biotechnology “Vector” of Rospotrebnadzor
- Issue: Vol 68, No 2 (2023)
- Pages: 152-160
- Section: ORIGINAL RESEARCH
- URL: https://journals.rcsi.science/0507-4088/article/view/132627
- DOI: https://doi.org/10.36233/0507-4088-168
- EDN: https://elibrary.ru/gewqpk
- ID: 132627
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Abstract
Introduction. The COVID-19 pandemic combined with seasonal epidemics of respiratory viral diseases requires targeted antiviral prophylaxis with restorative and immunostimulant drugs. The compounds of natural origin are low-toxic, but active against several viruses at the same time. One of the most famous compounds is Inonotus obliquus aqueous extract. The fruit body of basidial fungus I. obliquus is called Chaga mushroom.
The aim of the work ‒ was to study the antiviral activity of I. obliquus aqueous extract against the SARS-CoV-2 virus in vivo.
Materials and methods. Antiviral activity of I. obliquus aqueous extract sample (#20-17) was analyzed against strain of SARS-CoV-2 Omicron ВА.5.2 virus. The experiments were carried out in BALB/c inbred mice. The SARS-CoV-2 viral load was measured using quantitative real-time PCR combined with reverse transcription. The severity of lung tissue damage was assessed by histological methods.
Results. The peak values of the viral load in murine lung tissues were determined 72 hours after intranasal inoculation at dose of 2,85 lg TCID50. The quantitative real-time PCR testing has shown a significant decrease in the viral load compared to the control group by 4,65 lg copies/ml and 5,72 lg copies/ml in the lung tissue and nasal cavity samples, respectively. Histological methods revealed that the decrease in the number and frequency of observed pathomorphological changes in murine lung tissues depended on the introduction of the compound under study.
Conclusion. The results obtained indicate the possibility of using basidial fungus Inonotus obliquus aqueous extract as a preventive agent against circulating variants of SARS-CoV-2 virus.
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##article.viewOnOriginalSite##About the authors
Andrey V. Shipovalov
State Research Center of Virology and Biotechnology “Vector” of Rospotrebnadzor
Author for correspondence.
Email: shipovalov_av@vector.nsc.ru
ORCID iD: 0000-0003-1201-8307
Researcher, Department «Collection of microorganisms»
Russian Federation, 630559, Koltsovo, Novosibirsk RegionGleb A. Kudrov
State Research Center of Virology and Biotechnology “Vector” of Rospotrebnadzor
Email: kudrov_ga@vector.nsc.ru
ORCID iD: 0000-0002-8251-7040
Junior Researcher, Department «Collection of microorganisms»
Russian Federation, 630559, Koltsovo, Novosibirsk RegionMikhail Yu. Kartashov
State Research Center of Virology and Biotechnology “Vector” of Rospotrebnadzor
Email: kartashov_myu@vector.nsc.ru
ORCID iD: 0000-0002-7857-6822
MD, Researcher, Department of Molecular Virology for Flaviviruses and Viral Hepatitis
Russian Federation, 630559, Koltsovo, Novosibirsk RegionIrina A. Drachkova
State Research Center of Virology and Biotechnology “Vector” of Rospotrebnadzor
Email: drachkova_ia@vector.nsc.ru
ORCID iD: 0000-0002-2522-1657
PhD (Biology), Researcher, Department «Collection of microorganisms»
Russian Federation, 630559, Koltsovo, Novosibirsk RegionOleg V. Pyankov
State Research Center of Virology and Biotechnology “Vector” of Rospotrebnadzor
Email: pyankov_ov@vector.nsc.ru
ORCID iD: 0000-0003-3340-8750
PhD (Biology), Head of Department «Collection of microorganisms»
Russian Federation, 630559, Koltsovo, Novosibirsk RegionVladimir V. Omigov
State Research Center of Virology and Biotechnology “Vector” of Rospotrebnadzor
Email: omigov_vv@vector.nsc.ru
ORCID iD: 0000-0002-2028-6099
MD, Leading Researcher, Department of microscopic research
Russian Federation, 630559, Koltsovo, Novosibirsk RegionOleg S. Taranov
State Research Center of Virology and Biotechnology “Vector” of Rospotrebnadzor
Email: taranov_os@vector.nsc.ru
ORCID iD: 0000-0002-6746-8092
Head of Department of microscopic research
Russian Federation, 630559, Koltsovo, Novosibirsk RegionTamara V. Teplyakova
State Research Center of Virology and Biotechnology “Vector” of Rospotrebnadzor
Email: teplyakova_tv@vector.nsc.ru
ORCID iD: 0000-0003-4754-5051
Doctor of sciences (Biology), Professor, Head of Laboratory of Mycology, Department of Biophysics and Environmental Research
Russian Federation, 630559, Koltsovo, Novosibirsk RegionReferences
- Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., et al. Novel Coronavirus Investigating and Research Team, A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020; 382(8): 727–33. https://doi.org/10.1056/NEJMoa2001017
- Zhang B., Zhou X., Qiu Y., Song Y., Feng F., Feng J., et al. Clinical characteristics of 82 death cases with COVID-19. PLoS One. 2020; 15(7): e0235458. https://doi.org/10.1371/journal.pone.0235458
- Tay M.Z., Poh C.M., Rénia L., MacAry P.A., Ng L.F.P. The trinity of COVID-19: Immunity, inflammation and intervention. Nat. Rev. Immunol. 2020; 20(6): 363–74. https://doi.org/10.1038/s41577-020-0311-8.4
- WHO. Coronavirus disease (COVID-19) dashboard; 2023. Available at: https://covid19.who.int
- Akimkin V.G., Semenenko T.A., Ugleva S.V., Dubodelov D.V., Kuzin S.N., Yatsyshina S.B., et al. COVID-19 in Russia: epidemiology and molecular genetic monitoring. Vestnik Rossiyskoy akademii meditsinskikh nauk. 2022; 77(4); 254–60. EDN: https://elibrary.ru/dozijs https://doi.org/10.15690/vramn2121 (in Russian)
- Kiseleva I.V., Larionova N.V., Grigor’eva E.P., Ksenafontov A.D., Al’ Farrukh M.A., Rudenko L.G. Salient features of circulating respiratory viruses in the pre- and pandemic influenza and COVID-19 seasons. Infektsiya i immunitet. 2021; 11(6): 1009–19. EDN: https://elibrary.ru/higkam https://doi.org/10.15789/2220-7619-SFO-1662 (in Russian)
- Bimonte S., Crispo A., Amore A., Celentano E., Cuomo A., Cascella M. Potential antiviral drugs for SARS-Cov-2 treatment: preclinical findings and ongoing clinical research. In Vivo. 2020; 34(3 Suppl.): 1597–602. https://doi.org/10.21873/invivo.11949
- Hamza A., Ghanekar S., Kumar D.S. Current trends in health-promoting potential and biomaterial applications of edible mushrooms for human wellness. Food Biosci. 2022; 51: 102290. https://doi.org/10.1016/j.fbio.2022.102290
- Teplyakova T.V., Kosogova T.A. Higher Mushrooms of Western Siberia as Promising Objects for Drug Biotechnology [Vysshie griby Zapadnoy Sibiri – perspektivnye ob”ekty dlya biotekhnologii lekarstvennykh preparatov]. Novosibirsk; 2014. (in Russian)
- Martel J., Ko Y.F., Ojcius D.M., Lu C.C., Chang C.J., Lin C.S., et al. Immunomodulatory properties of plants and mushrooms. Trends Pharmacol. Sci. 2017; 38(11): 967–81. https://doi.org/10.1016/j.tips.2017.07.006
- Lu Y., Jia Y., Xue Z., Li N., Liu J., Chen H. Recent developments in Inonotus obliquus (Chaga mushroom) polysaccharides: Isolation, structural characteristics, biological activities and application. Polymers. 2021; 13(9): 1441. https://doi.org/10.3390/polym13091441
- Pan H.H., Yu X.T., Li T., Wu H.L., Jiao C.W., Cai M.H., et al. Aqueous extract from a Chaga medicinal mushroom, Inonotus obliquus (higher basidiomycetes), prevents herpes simplex virus entry through inhibition of viral-induced membrane fusion. Int. J. Med. Mushrooms. 2013; 15(1): 29–38. https://doi.org/10.1615/intjmedmushr.v15.i1.40
- Nosik D.N., Nosik N.N., Teplyakova T.V., Lobach O.A., Kiseleva I.A., Kondrashina N.G., et al. Antiviral activity of extracts of basidiomycetes and humic compounds substances against human immunodeficiency virus (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus 1) and herpes simplex virus (Herpesviridae: Simplexvirus: Human alphaherpesvirus 1). Voprosy virusologii. 2020; 65(5): 276–83. https://doi.org/10.36233/0507-4088-2020-65-5-4 EDN: https://elibrary.ru/hfbppn (in Russian)
- Teplyakova T.V., Ilyicheva T.N., Markovich N.A. Prospects for the development of anti-influenza drugs based on medicinal mushrooms (review). Appl. Biochem. Microbiol. 2020; 56(5): 489–96. https://doi.org/10.1134/S0003683820050142 EDN: https://elibrary.ru/bggpif
- Garber A., Barnard L., Pickrell C. Review of whole plant extracts with activity against herpes simplex viruses in vitro and in vivo. J. Evid. Based. Integr. Med. 2021; 26: 2515690X20978394. https://doi.org/10.1177/2515690X20978394
- Chun S., Gopal J., Muthu M. Antioxidant activity of mushroom extracts/polysaccharides—Their antiviral properties and plausible antiCOVID-19 properties. Antioxidants. 2021; 10(12): 1899. https://doi.org/10.3390/antiox10121899
- Eid J.I., Das B., Al-Tuwaijri M.M., Basal W.T. Targeting SARS-CoV-2 with Chaga mushroom: An in silico study toward developing a natural antiviral compound. Food Sci. Nutr. 2021; 9(12): 6513–23. https://doi.org/10.1002/fsn3.2576
- Arunachalam K., Sasidharan S.P., Yang X. A concise review of mushrooms antiviral and immunomodulatory properties that may combat against COVID-19. Food Chem. Adv. 2022; 1: 100023. https://doi.org/10.1016/j.focha.2022.100023
- Teplyakova T.V., Pyankov O.V., Safatov A.S., Ovchinnikova A.S., Kosogova T.A., Skarnovich M.O., et al. Water extract of the Chaga medicinal mushroom, Inonotus obliquus (Agaricomycetes), inhibits SARS-CoV-2 replication in vero E6 and vero cell culture experiments. Int. J. Med. Mushrooms. 2022; 24(2): 23–30. https://doi.org/10.1615/IntJMedMushrooms.2021042012
- Rockx B., Kuiken T., Herfst S., Bestebroer T., Lamers M.M., Oude Munnink B.B., et al. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science. 2020; 368(6494): 1012–5. https://doi.org/10.1126/science.abb7314
- Gu H., Chen Q., Yang G., He L., Fan H., Deng Y.Q., et al. Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science. 2020; 369(6511): 1603–7. https://doi.org/10.1126/science.abc4730
- Teplyakova T.V., P’yankov O.V., Skarnovich M.O. Replication inhibitor SARS-CoV-2 based on a water extract of the fungus Inonotus obliquus. Patent RF № 2741714 C1; 2021. (in Russian)
- Reed L.J., Muench H. A simple method of estimating fifty per cent endpoints. Am. J. Hyg. 1938; 27(3): 493–7. https://doi.org/10.1093/oxfordjournals.aje.a118408
- FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units. Lab. Anim. 2014; 48(3): 178–92. https://doi.org/10.1177/0023677213516312
- Guide for the Care and Use of Laboratory Animals. Washington: National Academies Press; 2011. Available at: https://www.ncbi.nlm.nih.gov/books/NBK54050
- American Veterinary Medical Association. AVMA Guidelines for the Euthanasia of Animals: 2020 Edition. Available at: https://www.avma.org/sites/default/files/2020-02/Guidelines-on-Euthanasia-2020.pdf
- Mironov A.N., Bunatyan N.D., Vasil’ev A.N. Methodological Recommendations for the Study of the Specific Activity of Interferon Inducers [Rukovodstvo po provedeniyu doklinicheskikh issledovaniy lekarstvennykh sredstv]. Moscow: Grif & K; 2012. (in Russian)
- Razumov I.A., Kazachinskaya E.I., Puchkova L.I., Kosogova T.A., Gorbunova I.A., Loktev V.B., et al. Protective activity of aqueous extracts from higher mushrooms against herpes sipmlex virus type-2 on albino mice model. Antibiotiki i khimioterapiya. 2013; 58(9-10): 8–12. EDN: https://elibrary.ru/nfgiex (in Russian)
- Basal W.T., Elfiky A., Eid J. Chaga medicinal mushroom Inonotus obliquus (Agaricomycetes) terpenoids may interfere with SARS-CoV-2 spike protein recognition of the host cell: a molecular docking study. Int. J. Med. Mushrooms. 2021; 23(3): 1–14. https://doi.org/10.1615/IntJMedMushrooms.2021037942
- Zhou H., Møhlenberg M., Thakor J.C., Tuli H.S., Wang P., Assaraf Y.G., et al. Sensitivity to vaccines, therapeutic antibodies, and viral entry inhibitors and advances to counter the SARS-CoV-2 Omicron variant. Clin. Microbiol. Rev. 2022; 35(3): e00014–22. https://doi.org/10.1128/cmr.00014-22
- Shipovalov A.V., Kudrov G.A., Tomilov A.A., Bodnev S.A., Boldyrev N.D., Ovchinnikova A.S., et al. Susceptibility to SARS-COV-2 virus variants of concern in mouse models. Problemy osobo opasnykh infektsiy. 2022; (1): 148–55. https://doi.org/10.21055/0370-1069-2022-1-148-155 (in Russian)
- Zhang Y.N., Zhang Z.R., Zhang H.Q., Li N., Zhang Q.Y., Li X.D., et al. Different pathogenesis of SARS-CoV-2 Omicron variant in wild-type laboratory mice and hamsters. Signal Transduct. Target. Ther. 2022; 7(1): 62. https://doi.org/10.1038/s41392-022-00930-2
- Halfmann P.J., Iida S., Iwatsuki-Horimoto K., Maemura T., Kiso M., Scheaffer S.M., et al. SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters. Nature. 2022; 603(7902): 687–92. https://doi.org/10.1038/s41586-022-04441-6