Review articles
doi: 10.25005/2074-0581-2022-24-1-113-122
BOTANICALS AS PROSPECTIVE AGENTS AGAINST SARS-COV-2 VIRUS

V. Dushenkov1, A. Dushenkov2

1Hostos Community College, City University of New York, Bronx, New York, US A
2School of Pharmacy and Health Sciences, Fairleigh Dickinson University, Florham Park, NJ, US A

Objective: To assess the potential role of botanicals as therapeutic agents against the SARS-CoV-2 virus.

Methods: This narrative review examined the potential role of botanicals as therapeutic agents against the SARS-CoV-2 virus based on the references limited to the English language and published up to February 2022 and retrieved from common academic search engines using multiple keywords and their combinations. The scientific names of plant species were confirmed using World Flora Online (https://wfoplantlist.org/).

Results: The role of botanicals in targeting druggable points in the virus replication cycle has been evaluated. This includes the potential role of phytochemicals and medicinal plant concoctions in preventing the virus from entering the cell. Furthermore, the agents have been shown to hinder the attachment of S protein to angiotensin-converting enzyme 2, block RNA-dependent RNA Polymerase, inhibit 3-chymotrypsin like protease, main protease, neuraminidase, and other enzymes involved in virus replication. Special attention was played to the role of botanicals as immunomodulators and adaptogens.

Conclusion: Botanicals have a high potential as prospective agents in managing viral diseases. Botanicals' mode of action(s) may be based on their direct interference with the virus's ability to enter human cells, virus replication, or their activation of the immune-modulatory and anti-inflammatory responses. In addition, the adjuvant treatments with botanicals have the potential to result in advances in symptom resolution, decrease disease burden and shorten disease duration.

Keywords: COVID-19, botanicals, herbal drugs, Ayurveda, nutraceuticals, phytochemicals, dietary supplements.

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References
  1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. NEJM. 2020;(382):727-33. Available from: https://doi.org/10.1056/NEJMoa2001017
  2. Chan YA, Zhan SH. The emergence of the spike furin cleavage site in SARSCoV-2. Molecular Biology and Evolution. 202
  3. Ruiz-Medina BE, Varela-Ramirez A, Kirken RA, Robles-Escajeda E. The SARSCoV-2 origin dilemma: Zoonotic transfer or laboratory leak? BioEssays. 2022;44(1):2100189. Available from: https://doi.org/10.1002/bies.202100189
  4. Liang G, Bushman FD. The human virome: Assembly, composition and host interactions. Nature Reviews Microbiology. 2021;19(8):514-27. Available from: https://doi.org/10.1038/s41579-021-00536-5
  5. Bai G-H, Lin S-C, Hsu Y-H, Chen S-Y. The human virome: Viral metagenomics, relations with human diseases, and therapeutic applications. Viruses. 2022;14(2):278. Available from: https://doi.org/10.3390/v14020278
  6. Souilmi Y, Lauterbur ME, Tobler R, Huber CD, Johar AS, Moradi SV, et al. An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East AsiA. Current Biology. 2021;31(16):3504-14. e9; Available from: https://doi.org/10.1016/j.cub.2021.05.067
  7. Zheng C, Shao W, Chen X, Zhang B, Wang G, Zhang W. Real-world effectiveness of COVID-19 vaccines: A literature review and meta-analysis. International Journal of Infectious Diseases. 2022;114:252-60. Available from: https://doi. org/10.1016/j.ijid.2021.11.009
  8. Sprent J, King C. COVID-19 vaccine side effects: The positives about feeling bad. Science Immunology. 2021;6(60):eabj9256. Available from: https://doi. org/10.1126/sciimmunol.abj9256
  9. Jassim SA, Naji MA. Novel antiviral agents: A medicinal plant perspective. Journal of Applied Microbiology. 2003;95(3):412-27. Available from: https://doi. org/10.1046/j.1365-2672.2003.02026.x
  10. Musarra-Pizzo M, Pennisi R, Ben-Amor I, Mandalari G, Sciortino MT. Antiviral activity exerted by natural products against human viruses. Viruses. 2021;13(5):828. Available from: https://doi.org/10.3390/v13050828
  11. Garcia S. Pandemics and traditional plant-based remedies. A historicalbotanical review in the era of COVID19. Front Plant Sci. 2020;11:571042. Available from: https://doi.org/10.3389/fpls.2020.571042
  12. Moore M, Langland J. Sarracenia purperea: A botanical extract with antipapilloma virus and oncolytic activity. Integrative Medicine. 2018;17(2):61-61.
  13. Abascal K, Yarnell E. Herbal treatments for pandemic influenza: Learning from the eclectics' experience. Alternative & Complementary Therapies. 2006;12(5):214-21. Available from: https://doi.org/10.1089/act.2006.12.214
  14. Tamiflu. Package insert.: Gilead Sciences, Inc; 2012.
  15. Tao K, Tzou PL, Nouhin J, Bonilla H, Jagannathan P, Shafer RW. SARS-CoV-2 antiviral therapy. Clinical Microbiology Reviews. 2021;34(4):e00109-21. . Available from: https://doi.org/10.1128/CMR.00109-21
  16. Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nature Reviews Molecular Cell Biology. 2022;23(1):3-20. . Available from: https://doi.org/10.1038/s41580-021-00418- x
  17. Ali S, Alam M, Khatoon F, Fatima U, Elasbali AM, Adnan M, et al. Natural products can be used in therapeutic management of COVID-19: Probable mechanistic insights. Biomedicine & Pharmacotherapy. 2022;147:112658. Available from: https://doi.org/10.1016/j.biophA. 2022.112658
  18. Españo E, Kim J, Lee K, Kim J-K. Phytochemicals for the treatment of COVID-19. Journal of Microbiology. 2021;59(11):959-77. Available from: https://doi. org/10.1007/s12275-021-1467-z
  19. Colunga Biancatelli RML, Berrill M, Catravas JD, Marik PE. Quercetin and vitamin C: An experimental, synergistic therapy for the prevention and treatment of SARS-CoV-2 related disease (COVID-19). Frontiers in Immunology. 2020;11:1451. . Available from: https://doi.org/10.3389/fimmu.2020.01451
  20. Goc A, Niedzwiecki A, Ivanov V, Ivanova S, Rath M. Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants. European Journal of Microbiology and Immunology. 2022;11(4):87-94. Available from: https://doi. org/10.1556/1886.2021.00022
  21. Zhang DH, Wu KL, Zhang X, Deng SQ, Peng B. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. Journal of Integrative Medicine. 2020;18(2):152-8. Available from: https://doi. org/10.1016/j.joim.2020.02.005
  22. Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B. 2020;10(5):766-88. Available from: https://doi.org/10.1016/j.apsb.2020.02.008
  23. Napolitano F, Xu X, Gao X. Impact of computational approaches in the fight against COVID-19: An AI guided review of 17 000 studies. Briefings in Bioinformatics. 2022;23(1):bbab456. Available from: https://doi.org/10.1093/bib/ bbab456
  24. Rolta R, Salaria D, Sharma P, Sharma B, Kumar V, Rathi B, et al. Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua inhibit spike protein of SARS-CoV-2 binding to ACE2 receptor: In silico approach. Current Pharmacology Reports. 2021;7(4):135-49. Available from: https://doi.org/10.1007/ s40495-021-00259-4
  25. Goc A, Sumera W, Rath M, Niedzwiecki A. Phenolic compounds disrupt spikemediated receptor-binding and entry of SARS-CoV-2 pseudo-virions. PLoS One. 2021;16(6):e0253489. Available from: https://doi.org/10.1371/journal. pone.0253489
  26. Xu H, Liu B, Xiao Z, Zhou M, Ge L, Jia F, et al. Computational and experimental studies reveal that thymoquinone blocks the entry of coronaviruses into in vitro cells. Infectious Diseases and Therapy. 2021;10(1):483-94. Available from: https://doi.org/10.1007/s40121-021-00400-2
  27. Koulgi S, Jani V, Uppuladinne VN M, Sonavane U, Joshi R. Natural plant products as potential inhibitors of RNA dependent RNA polymerase of Severe Acute Respiratory Syndrome Coronavirus-2. PLoS One. 2021;16(5):e0251801. Available from: https://doi.org/10.1371/journal.pone.0251801
  28. Naidu SA, Mustafa G, Clemens RA, Naidu AS. Plant-derived natural nonnucleoside analog inhibitors (NNAIs) against RNA-dependent RNA polymerase complex (nsp7/nsp8/nsp12) of SARS-CoV-2. Journal of Dietary Supplements. 2021:1-30. Available from: https://doi.org/10.1080/19390211.2021.2006387
  29. Mishra P, Sohrab S, Mishra SK. A review on the phytochemical and pharmacological properties of Hyptis suaveolens (L.) Poit. Future Journal of Pharmaceutical Sciences. 2021;7(1):1-11. Available from: https://doi. org/10.1186/s43094-021-00219-1
  30. Halder P, Pal U, Paladhi P, Dutta S, Paul P, Pal S, et al. Evaluation of potency of the selected bioactive molecules from Indian medicinal plants with MPro of SARS-CoV-2 through in silico analysis. Journal of Ayurveda and Integrative Medicine. 2022;13(2):100449. Available from: https://doi.org/10.1016/j. jaim.2021.05.003
  31. Bahun M, Jukić M, Oblak D, Kranjc L, Bajc G, Butala M, et al. Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols. Food Chemistry. 2022;373:131594. Available from: https://doi.org/10.1016/j. foodchem.2021.131594
  32. Shree P, Mishra P, Selvaraj C, Singh SK, Chaube R, Garg N, et al. Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants – Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) – a molecular docking study. Journal of Biomolecular Structure and Dynamics. 2022;40(1):190-203. Available from: https://doi.org/10.1080/07391102.2020.1810778
  33. Theisen LL, Muller CP. EPs® 7630 (Umckaloabo®), an extract from Pelargonium sidoides roots, exerts anti-influenza virus activity in vitro and in vivo. Antiviral Research. 2012;94(2):147-56. Available from: https://doi.org/10.1016/j. antiviral.2012.03.006
  34. Theisen LL, Erdelmeier CA, Spoden GA, Boukhallouk F, Sausy A, Florin L, et al. Tannins from Hamamelis virginiana bark extract: Characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus. PloS One. 2014;9(1):e88062. Available from: https://doi. org/10.1371/journal.pone.0088062
  35. Döring K, Langeder J, Duwe S, Tahir A, Grienke U, Rollinger JM, et al. Insights into the direct anti-influenza virus mode of action of Rhodiola rosea. Phytomedicine. 2022;96:153895. Available from: https://doi.org/10.1016/j. phymed.2021.153895
  36. Nguyen LC, Yang D, Nicolaescu V, Best TJ, Gula H, Saxena D, et al. Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses. Science Advances. 2022:eabi6110. Available from: https://doi.org/10.1126/sciadv.abi6110
  37. Farahani M, Niknam Z, Amirabad LM, Amiri-Dashatan N, Koushki M, Nemati M, et al. Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets. Biomedicine & Pharmacotherapy. 2022;145:112420. Available from: https://doi.org/10.1016/j.biophA. 2021.112420
  38. Pan M-H, Lai C-S, Dushenkov S, Ho C-T. Modulation of inflammatory genes by natural dietary bioactive compounds. Journal of Agricultural and Food Chemistry. 2009;57(11):4467-77. Available from: https://doi.org/10.1021/jf900612n
  39. Agarwal H, Shanmugam VK. Mechanism-based approach of medicinal plants mediated treatment of inflammatory disorders: A review. South African Journal of Botany. 2022;147:380-90. Available from: https://doi.org/10.1016/j. sajb.2022.01.018
  40. Duan X, Li Y, Xu F, Ding H. Study on the neuroprotective effects of Genistein on Alzheimer's disease. Brain and Behavior. 2021;11(5):e02100. Available from: https://doi.org/10.1002/brb3.2100
  41. Zhu J, Deng Y-Q, Wang X, Li X-F, Zhang N-N, Liu Z, et al. An artificial intelligence system reveals liquiritin inhibits SARS-CoV-2 by mimicking type I interferon. BioRxiv. 2020. Available from: https://doi.org/10.1101/2020.05.02.074021
  42. Dey M, Ripoll C, Pouleva R, Dorn R, Aranovich I, Zaurov D, et al. Plant extracts from Central Asia showing anti-inflammatory activities in gene expression assays. Phytotherapy Research. 2008;22(7):929-34. Available from: https:// doi.org/10.1002/ptr.2427
  43. Brendler T, Al-Harrasi A, Bauer R, Gafner S, Hardy ML, Heinrich M, et al. Botanical drugs and supplements affecting the immune response in the time of COVID-19: Implications for research and clinical practice. Phytotherapy Research. 2021;35(6):3013-31. Available from: https://doi.org/10.1002/ptr.7008
  44. Singh T, Nigam A, Kapila R. Analyzing the use of vedicinal herbs during the first wave and second wave of COVID-19. Proceedings of the National Academy of Sciences, India Section B: Biological Sciences. 2022:1-4. Available from: https:// doi.org/10.1007/s40011-021-01303-5
  45. Parbat AY, Malode GP, Shaikh AR, Panchale WA, Manwar JV, Bakal RL. Ethnopharmacological review of traditional medicinal plants as immunomodulator. World Journal of Biology Pharmacy and Health Sciences. 2021;6(2):043-55. Available from: https://doi.org/10.30574/ wjbphs.2021.6.2.0048
  46. Kumar D, Arya V, Kaur R, Bhat ZA, Gupta VK, Kumar V. A review of immunomodulators in the Indian traditional health care system. Journal of Microbiology, Immunology and Infection. 2012;45(3):165-84. Available from: https://doi.org/10.1016/j.jmii.2011.09.030
  47. Panossian AG, Efferth T, Shikov AN, Pozharitskaya ON, Kuchta K, Mukherjee PK, et al. Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases. Medicinal Research Reviews. 2021;41(1):630-703. Available from: https://doi.org/10.1002/ med.21743
  48. Jalali A, Dabaghian F, Akbrialiabad H, Foroughinia F, Zarshenas MM. A pharmacology-based comprehensive review on medicinal plants and phytoactive constituents possibly effective in the management of COVID-19. Phytotherapy Research. 2021;35(4):1925-38. Available from: https://doi. org/10.1002/ptr.6936
  49. Lyu M, Fan G, Xiao G, Wang T, Xu D, Gao J, et al. Traditional Chinese medicine in COVID-19. Acta Pharmaceutica Sinica B. 2021;11(11):3337-63. Available from: https://doi.org/10.1016/j.apsb.2021.09.008.

Authors' information:

Vyacheslav Dushenkov
Ph.D., Professor, Natural Sciences Department, Hostos Community College, City University of New York
Researcher ID: AAE-8520-2019
Scopus ID: 6507356097
ORCID ID: 0000-0001-5176-7461
E-mail: vdushenkov@hostos.cuny.edu

Anna Dushenkov
BSPharm., Pharm.D., BSPS, R.Ph., School of Pharmacy and Health Sciences, Fairleigh Dickinson University
ORCID ID: 0000-0001-6800-2190
Scopus ID: 57194109100
E-mail: annads@fdu.edu

Information about support in the form of grants, equipment, medications

Research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health under Award Number D43TW009672. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors did not receive financial support from manufacturers of medicines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Vyacheslav Dushenkov
Ph.D. Professor, Natural Sciences Department, Hostos Community College, City University of New York

500 Grand Concourse, Bronx, New York, USA, 10451

Tel.: +1 (718) 5184444

E-mail: vdushenkov@hostos.cuny.edu

Materials on the topic:
  1. HISTORY OF ADOLESCENT MEDICINE AS A SCIENTIFIC DISCIPLINE IN THE KYRGYZ REPUBLIC
  2. COVID-19 AND WOMEN'S REPRODUCTIVE HEALTH
  3. POPULATION HEALTH STATUS AS ONE OF THE INDICATORS OF MODERN SOCIETY DEVELOPMENT

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