Natural therapeutics against SARS CoV2: the potentiality and challenges

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Review Articles | Published:

Print ISSN : 0970-4078.
Online ISSN : 2229-4473.
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Doi: 10.1007/s42535-022-00401-7
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Keywords: Covid-19, Natural medicine, Nutraceuticals, Plant metabolites, Therapeutics


The incidence of the COVID-19 pandemic completely reoriented global socio-economic parameters and human civilization have experienced the worst situation in the recent past. The rapid mutation rates in viruses have continuously been creating emerging variants of concerns (VOCs) which devastated different parts of the world with subsequent waves of infection. Although, series of antiviral drugs and vaccines were formulated but cent percent effectiveness of these drugs is still awaited. Many of these drugs have different side effects which necessitate proper trial before release. Plants are the storehouse of antimicrobial metabolites which have also long been utilized as traditional medicines against different viral infections. Although, proper mechanism of action of these traditional medicines are unknown, they may be a potential source of effective anti-COVID drug for future implications. Advanced bioinformatic applications have opened up a new arena in predicting these repurposed drugs as a potential COVID mitigator. The present review summarizes brief accounts of the corona virus with their possible entry mechanism. This study also tries to classify different possible anti COVID-19 plant-derived metabolites based on their probable mode of action. This review will surely provide useful information on repurposed drugs to combat COVID-19 in this critical situation.


Alhazmi HA, Najmi A, Javed SA, Sultana S, Al Bratty M, Makeen HA, Meraya AM, Ahsan W, Mohan S, Taha MM, Khalid A (2021) Medicinal plants and isolated molecules demonstrating immunomodulation activity as potential alternative therapies for viral diseases including COVID-19. Front Immunol 12:637553.

Andrade BS, Ghosh P, Barh D, Tiwari S, Silva RJS, de Assis Soares WR, Melo TS, Freitas AS, González-Grande P, Palmeira LS, Alcantara LCJ (2020) Computational screening for potential drug candidates against the SARS-CoV-2 main protease. F1000 Res 9:514.

Azim KF, Ahmed SR, Banik A, Khan MMR, Deb A, Somana SR (2020) Screening and druggability analysis of some plant metabolites against SARS-CoV-2: an integrative computational approach. Inf Med Unlocked 20:100367.

Bhar A (2021) Is it possible to ensure COVID19 vaccine supply by using plants? Nucleus 64:137–141.

Bleasel MD, Peterson GM (2020) Emetine, ipecac, ipecac alkaloids and analogues as potential antiviral agents for coronaviruses. Pharmaceuticals 13:51.

Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, van der Meer F, Kallio K, Kaya T, Anastasina M, Smura T (2020) Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 370:856–860.

Daly JL, Simonetti B, Klein K, Chen KE, Williamson MK, Antón-Plágaro C, Shoemark DK, Simón-Gracia L, Bauer M, Hollandi R, Greber UF (2020) Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 370:861–865.

Das SK, Mahanta S, Tanti B, Tag H, Hui PK (2022) Identification of phytocompounds from Houttuynia cordata Thunb. as potential inhibitors for SARS-CoV-2 replication proteins through GC–MS/LC–MS characterization, molecular docking and molecular dynamics simulation. Mol Divers 7:1–24.

Ekor M (2014) The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 4:177.

El-Demerdash A, Metwaly AM, Hassan A, El-Aziz A, Mohamed T, Elkaeed EB, Eissa IH, Arafa RK, Stockand JD (2021) Comprehensive virtual screening of the antiviral potentialities of marine polycyclic guanidine alkaloids against SARS-CoV-2 (COVID-19). Biomolecules 11:460.

Enmozhi SK, Raja K, Sebastine I, Joseph J (2021) Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in-silico approach. J Biomol Struct Dyn 39:3092–3098.

Ghoran SH, El-Shazly M, Sekeroglu N, Kijjoa A (2021) Natural products from medicinal plants with anti-human coronavirus activities. Molecules 26:1754.

Gogoi B, Chowdhury P, Goswami N, Gogoi N, Naiya T, Chetia P, Mahanta S, Chetia D, Tanti B, Borah P, Handique PJ (2021) Identification of potential plant-based inhibitor against viral proteases of SARS-CoV-2 through molecular docking, MM-PBSA binding energy calculations and molecular dynamics simulation. Mol Divers 25:1963–1977.

Hatmal MMM, Alshaer W, Al-Hatamleh MA, Hatmal M, Smadi O, Taha MO, Oweida AJ, Boer JC, Mohamud R, Plebanski M (2020) Comprehensive structural and molecular comparison of spike proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, and their interactions with ACE2. Cells 9:2638.

Helmy YA, Fawzy M, Elaswad A, Sobieh A, Kenney SP, Shehata AA (2020) The COVID-19 pandemic: a comprehensive review of taxonomy, genetics, epidemiology, diagnosis, treatment, and control. J Clin Med 9:1225.

Henss L, Auste A, Schürmann C, Schmidt C, von Rhein C, Mühlebach MD, Schnierle BS (2021) The green tea catechin epigallocatechin gallate inhibits SARS-CoV-2 infection. J Gen Virol 102:001574.

Huang Y, Yang C, Xu XF, Xu W, Liu SW (2020) Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 41:1141–1149.

Jain S (2021) Diet and nutrition recommendations during the COVID-19 pandemic. IP J Nutri Metab Health Sci 3:114–118.

Javed H, Meeran MFN, Jha NK, Ojha S (2020) Carvacrol, a plant metabolite targeting viral protease (Mpro) and ACE2 in host cells can be a possible candidate for COVID-19. Front Plant Sci 11:601335.

Jomhori M, Mosaddeghi H (2021) Molecular modeling of natural and synthesized inhibitors against SARS-CoV-2 spike glycoprotein. Res Biomed Eng.

Keyaerts E, Vijgen L, Pannecouque C, Van Damme E, Peumans W, Egberink H, Balzarini J, Van Ranst M (2007) Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle. Antiviral Res 75:179–187.

Lawal IO, Omogbene TO (2021) Nigerian polyherbal-based hydrotherapy: a panacea to infectious diseases. Herba Pol 67:65–79.

Lawal IO, Olufade II, Rafiu BO, Aremu AO (2020) Ethnobotanical survey of plants used for treating cough associated with respiratory conditions in Ede South local government area of Osun State, Nigeria. Plants 9:647.

Lee H, Lei H, Santarsiero BD, Gatuz JL, Cao S, Rice AJ, Patel K, Szypulinski MZ, Ojeda I, Ghosh AK, Johnson ME (2015) Inhibitor recognition specificity of MERS-CoV papain-like protease may differ from that of SARS-CoV. ACS Chem Biol 10:1456–1465.

Li F (2016) Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol 3:237–261.

Li Z, Li X, Huang YY, Wu Y, Liu R, Zhou L, Lin Y, Wu D, Zhang L, Liu H, Xu X (2020) Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs. Proc Natl Acad Sci 117:27381–27387.

Lin M, Wynne J, Lei Y, Wang T, Curran WJ, Liu T, Yang X (2021) Artificial intelligence in tumor subregion analysis based on medical imaging: a review. J Appl Clin Med Phys 22:10–26.

Liu X, Raghuvanshi R, Ceylan FD, Bolling BW (2020) Quercetin and its metabolites inhibit recombinant human angiotensin-converting enzyme 2 (ACE2) activity. J Agric Food Chem 68:13982–13989.

Luan J, Lu Y, Jin X, Zhang L (2020) Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection. Biochem Biophys Res Commun 526:165–169.

Lucas K, Fröhlich-Nowoisky J, Oppitz N, Ackermann M (2021) Cinnamon and hop extracts as potential immunomodulators for severe COVID-19 cases. Front Plant Sci 12:263.

Manoharan Y, Haridas V, Vasanthakumar KC, Muthu S, Thavoorullah FF, Shetty P (2020) Curcumin: a wonder drug as a preventive measure for COVID19 management. Ind J Clin Biochem 35:373–375.

Matsuura HN, Fett-Neto AG (2015) Plant alkaloids: main features, toxicity, and mechanisms of action. Plant Toxins 2:1–15.

Maurya S, Sangwan NS (2020) Profiling of essential oil constituents in Ocimum species. Proc Natl Acad Sci India Sect B Biol Sci 90:577–583.

Mpiana PT, Tshibangu DS, Kilembe JT, Gbolo BZ, Mwanangombo DT, Inkoto CL, Lengbiye EM, Mbadiko CM, Matondo A, Bongo GN, Tshilanda DD (2020) Identification of potential inhibitors of SARS-CoV-2 main protease from Aloe vera compounds: a molecular docking study. Chem Phys Lett 754:137751.

Muchtaridi M, Fauzi M, Khairul Ikram NK, MohdGazzali A, Wahab HA (2020) Natural flavonoids as potential angiotensin-converting enzyme 2 inhibitors for anti-SARS-CoV-2. Molecules 25:3980.

Noor H, Ikram A, Rathinavel T, Kumarasamy S, Nasir Iqbal M, Bashir Z (2021) Immunomodulatory and anti-cytokine therapeutic potential of curcumin and its derivatives for treating COVID-19—a computational modeling. J Biomol Struct Dyn 9:1–16.

Özçelik B, Kartal M, Orhan I (2011) Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids. Pharm Biol 49:396–402.

Parvez MSA, Azim KF, Imran AS, Raihan T, Begum A, Shammi TS, Howlader S, Bhuiyan FR, Hasan M (2020) Virtual screening of plant metabolites against main protease, RNA-dependent RNA polymerase and Spike protein of SARS-CoV-2: therapeutics option of COVID-19. arXiv preprint arXiv:2005.11254

Paul D, Mahanta S, Tag H, Das SK, Das Gupta D, Tanti B, Ananthan R, Das R, Jambhulkar S, Hui PK (2021) Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK-HER2 and VEGFR2 receptors, by in silico approach. Mol Divers 23:1–23.

Peng J, Zheng TT, Li X, Liang Y, Wang LJ, Huang YC, Xiao HT (2019) Plant-derived alkaloids: the promising disease-modifying agents for inflammatory bowel disease. Front Pharmacol 10:351.

Puttaswamy H, Gowtham HG, Ojha MD, Yadav A, Choudhir G, Raguraman V, Kongkham B, Selvaraju K, Shareef S, Gehlot P, Ahamed F (2020) In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis. Sci Rep 10:1–24.

Sampangi-Ramaiah MH, Vishwakarma R, Shaanker RU (2020) Molecular docking analysis of selected natural products from plants for inhibition of SARS-CoV-2 main protease. Curr Sci 118:1087–1092

Senthil Kumar KJ, Gokila Vani M, Wang CS, Chen CC, Chen YC, Lu LP, Huang CH, Lai CS, Wang SY (2020) Geranium and lemon essential oils and their active compounds downregulate angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike receptor-binding domain, in epithelial cells. Plants 9:770.

Sheehan SA, Hamilton KL, Retzbach EP, Balachandran P, Krishnan H, Leone P, Lopez-Gonzalez M, Suryavanshi S, Kumar P, Russo R, Goldberg GS (2021) Evidence that Maackiaamurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells with potential to inhibit SARS-CoV-2 infection and COVID-19 disease progression. Exp Cell Res 403:112594.

Sinha N, Balayla G (2020) Hydroxychloroquine and Covid-19. Postgrad Med J 96:550–555.

Tallei TE, Tumilaar SG, Niode NJ, Kepel BJ, Idroes R, Effendi Y, Sakib SA, Emran TB (2020) Potential of plant bioactive compounds as SARS-CoV-2 main protease (Mpro) and spike (S) glycoprotein inhibitors: a molecular docking study. Scientifica.

Thimmulappa RK, Kumar MNK, Shivamallu C, Subramaniam KT, Radhakrishnan A, Suresh B, Kuppusamy G (2021) Antiviral and immunomodulatory activity of curcumin: a case for prophylactic therapy for COVID-19. Heliyon.

Tito A, Colantuono A, Pirone L, Pedone E, Intartaglia D, Giamundo G, Conte I, Vitaglione P, Apone F (2021) Pomegranate peel extract as an inhibitor of SARS-CoV-2 spike binding to human ACE2 receptor (in vitro): a promising source of novel antiviral drugs. Front Chem 9:638187.

Troost B, Mulder LM, Diosa-Toro M, van de Pol D, Rodenhuis-Zybert IA, Smit JM (2020) Tomatidine, a natural steroidal alkaloid shows antiviral activity towards chikungunya virus in vitro. Sci Rep 10:1–12.

Ullrich S, Nitsche C (2020) The SARS-CoV-2 main protease as drug target. Bioorg Med Chem Lett 30:127377.

van Oosterhout C, Hall N, Ly H, Tyler KM (2021) COVID-19 evolution during the pandemic—implications of new SARS-CoV-2 variants on disease control and public health policies. Virulence 12:2013–2016.

Wang K, Chen W, Zhang Z, Deng Y, Lian JQ, Du P, Wei D, Zhang Y, Sun XX, Gong L, Yang X (2020a) CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal Transduct Target Ther 5:1–10.

Wang T, Du Z, Zhu F, Cao Z, An Y, Gao Y, Jiang B (2020b) Comorbidities and multi-organ injuries in the treatment of COVID-19. Lancet 395:e52.

Warowicka A, Nawrot R, Goździcka-Józefiak A (2020) Antiviral activity of berberine. Arch Virol 165:1935–1945.

Wielgat P, Rogowski K, Godlewska K, Car H (2020) Coronaviruses: is sialic acid a gate to the eye of cytokine storm? From the entry to the effects. Cells 9:1963.

Wink M (2020) Potential of DNA intercalating alkaloids and other plant secondary metabolites against SARS-CoV-2 causing COVID-19. Diversity 12:175.

Xu J, Xu Z, Zheng W (2017) A review of the antiviral role of green tea catechins. Molecules 22:1337.

Yang Y (2020) Use of herbal drugs to treat Covid-19 should be with caution. Lancet 395:1689–1690.

Yo EC, Kadharusman MM, Karman AP, Louisa M, Arozal W (2021) Potential pharmacological options and new avenues using inhaled curcumin nanoformulations for treatment of post-COVID-19 fibrosis. Syst Rev Pharm 12:1119–1128

Zhang DH, Wu KL, Zhang X, Deng SQ, Peng B (2020) In silico screening of Chinese herbal medicines with the potential to directly inhibit novel coronavirus. J Integr Med 18:152–158.

Zotchev SB (2013) Alkaloids from marine bacteria. Adv Bot Res 68:301–333.



The authors express sincere thanks to respected Editor of the journal and anonymous reviewers for suggestions to improve the quality of the manuscript.

Author Information

Bhar Anirban
Post Graduate Department of Botany, Ramakrishna Mission Vivekananda Centenary College, Kolkata, India
Jain Akansha
Division of Plant Biology, Bose Institute, Kolkata, India

Das Sampa
Division of Plant Biology, Bose Institute, Kolkata, India