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Journal of Pharmacognosy and Phytochemistry 2020; 9(3): 1221-1223
E-ISSN: 2278-4136
P-ISSN: 2349-8234
www.phytojournal.com
JPP 2020; 9(3): 1221-1223
Received: 12-03-2020
Accepted: 16-04-2020
Ritav Viralbhai Brahmbhatt
1. M.Pharm Herbal Drug
Technology (HDT), The
Maharaja Sayajirao University
(MSU), Vadodara(D),
Gujarat(S), India
2. The Himalaya Drug Company
Associate-Product
Management Team,
Bengaluru, Karnataka, India
Corresponding Author:
Ritav Viralbhai Brahmbhatt
1. M.Pharm Herbal Drug
Technology (HDT), The
Maharaja Sayajirao University
(MSU), Vadodara(D),
Gujarat(S), India
2. The Himalaya Drug Company
Associate-Product
Management Team,
Bengaluru, Karnataka, India
Herbal medicines in management and prevention
of COVID-19
Ritav Viralbhai Brahmbhatt
DOI: https://doi.org/10.22271/phyto.2020.v9.i3t.11460
Abstract
Traditional herbal medicines are widely accepted in the world. Certain countries and WHO have research
investment in traditional herbal medicines. COVID-19 came as a major Health care challenge for human
in 2019. 480 deaths have been recorded till 18th of April 2020 in India. No pharmaceutical products have
yet been shown to be safe and effective for the treatment of COVID-19. Major 3 types of targets of
COVID-19 were identified by researches, which are as follow 1) Inhibit coronavirus at structural level,
2) Inhibit coronavirus RNA synthesis and replication and 3) Inhibit virulence factor of Coronavirus.
Certain Herbal medicines like Tribulus terrestris, Withania somnifera, Curcuma longa, Ocimum
sanctum, Phyllanthus emblica have potent Anti-COVID properties.
Keywords: Traditional herbal medicine, COVID-19, Structural levels, RNA synthesis, Tribulus
terrestris, Withania somnifera, Curcuma longa, Ocimum sanctum, Phyllanthus emblica
1. Introduction
Traditional herbal medicines are getting significant attention in global health debates. India,
United States of America (USA), China, Nigeria and World Health Organization - WHO have
all made substantial research investments in traditional herbal medicines [1].
Herbal medicine finds itself in a race to develop new medicines, with fewer or no adverse
effects, for therapeutic and preventive application in illnesses [2].
As per the Ministry of Health and Family welfare, Government of India, their are 11, 906
Active Cases of COVID-19. 480 deaths has been reported, 1991 patients were discharged till
18th April 2020 [3].
But Still, no pharmaceutical products have yet been shown to be safe and effective for the
treatment of COVID-19. However, a number of medicines have been suggested as potential
investigational therapies, many of which are now being or will soon be studied in clinical
trials, including the SOLIDARITY trial co-sponsored by WHO and participating countries [4].
1.1 Targets of COVID-19
Table 1: Enlist the major targets of COVID-19
Sr No.
Major Targets of COVID-19
#
Inhibit SARS-CoV-2 RNA synthesis and
replication
Inhibit SARS-CoV-
2 at structural level
Inhibit virulence factor
of SARS-CoV-2
1
Papain-like protease (PLpro)
Spike Protein
Nsp1
2
3C-like main protease (3CLpro)
E protein Or N protein
Nsp3c
3
RNA-dependent RNA polymerase (RdRp)
-
ORF7
4
Helicase
-
-
1.2 Major 3 types of targets of COVID-19 are
1. Inhibit coronavirus at structural level
2. Inhibit coronavirus RNA synthesis and replication
3. Inhibit virulence factor of Coronavirus [5].
2. Effective Herbal Plants in COVID-19
Certain natural products from Indian natural medicines, bind to the active sites of COVID-19
proteases, hence are likely to hinder viral replication [6].
2.1 Tribulus terrestris
Tribulus terrestris fruits are well known for their usage in pharmaceutical preparations and
food supplements. The methanol extract of T. terrestris fruits showed potent inhibition against
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Journal of Pharmacognosy and Phytochemistry http://www.phytojournal.com
papain-like protease (PLpro), an essential proteolylic enzyme
for protection to pathogenic virus and bacteria.
Major bioactive compounds, are six cinnamic amides and
ferulic acid, were showing inhibition of Papain-like proteinase
(PLpro), which is major protein target of COVID-19 [7].
2.2 Withania somnifera
Withania somnifera contains variety of phytoconstituents like
Withanolide A & B, Withaferin A, Withanone, Withanosides
[6].
WSG (Withania somnifera glycoprotein) isolated from
Withania somnifera root tubers revealed (protease inhibitor)
antimicrobial activity against few bacterial and
phytopathogenic virus [9].
Withania somnifera would be an effective agent in the
management of COVID-19 through modulation of host Th-
1/Th-2 immunity. WS may be beneficial in inducing anti-viral
immunity (owing to increased IFN-gamma responses) and
optimum anti-inflammatory activities (down-regulation of IL-
1, IL-6, TNF-alpha and other inflammatory mediators), which
are the key targets relevant to COVID-19 [10].
As per the recent Molecular Docking Studies, Withanolide D,
Withaferin A, as most appropriate inhibitors against 3C-like
main protease (3CLpro), which can be further explored to test
against Coronavirus (COVID-19) in pre-clinical and clinical
settings [11].
Withanolide-B, Withanone and Withaferin-A, major
phytochemicals of Withania somnifera have predicted binding
energy lower than the pharmacological inhibitor, N3
The binding of these phytochemicals with main protease may
slow down the cleavage of PPs to releases NSPs and decrease
the process of viral replication and transcription [12].
2.3 Curcuma longa
Curcuma longa contain demethoxycurcumin, curcumin,
Diacetylcurcumin [13], as a major phytoconstituents, which are
the most recommended compounds found in medicinal plants
that may act as potential inhibitors of COVID-19 Main
Protein (Mpro) [14].
Curcumin is strongly bind to 3CL-protease of COVID19 in
comparison to the antimalaric drugs and promote important
structural changes in this viral protease, inducing folding of
the enzyme [15].
Diacetylcurcumin present in Curcuma longa have been found
as more effective on COVID-19 (Mpro) than Nelfinavir [16].
From the recent Docking studies, it can be concluded that
Binding energy of Curcumin (-38.84 kcal/mol) had greater
than hydroxychloroquine (HCQ) (-35.87 kcal/mol) in case of
S1 receptor binding domain. Therefor, Curcumin could be
used as combination therapy along with hydroxychloroquine
for disrupting the stability of SARS-CoV2 receptor proteins
[17].
Curcumin and HCQ interact with the C-terminal of S1
domain with binding energies of -7.1 and -5.6 Kcal/mol [18].
2.4 Ocimum sanctum
Ocimum sanctum extract can be included as a preventive
measure against COVID-19 due to its potential to inhibit
replication of COVID-19 supported with its immune-
modulatory feature and ACE II blocking properties. Ocimum
sanctum containing, Tulsinol (A, B, C, D, E, F, G) and
dihydrodieuginol-B inhibit SARS Coronavirus Main Protease
and Papain-like Protease [19].
Ocimum sanctum is being used in the management of pain,
diarrhea, cough and fever, which are the common symptoms
of COVID-19 [20].
Ocimum sanctum boosts the immunity of the body and helps
to defense the threatening virus and bacteria [21].
2.5 Phyllanthus emblica
Phyllanthus emblica also have immunomodulatory properties,
and may have the potential to bolster health and immunity of
the community in the fight against SARS-CoV-2 infection [10].
Phyllaemblicin-B and phyllaemblinol from Phyllanthus
emblica showed high binding affinity to helicase protein,
which is one of the major targets of COVID-19.
Phyllaemblicin G7 from Phyllanthus emblica exhibited high
binding affinity to the Spike Protein of COVID-19 [5].
The antioxidative and anti-inflammatory properties of
Phyllanthus emblica are the key to its therapeutic effect [22].
Table 2: Herbal medicines and its effective targets against COVID-19
Sr. no
Effective Targets of COVID-19
Ref.
1
Papain-like protease (PLpro)
(7)
2
3C-like Main protease (3CLpro)
(11)
3
3C-like Main protease (3CLpro)
(15)
4
Main Protease and Papain-like Protease.
(19)
5
Helicase protein and Spike Protein
(5)
Conclusion
Novel evidence based approach of Herbal medicine plays
preventive role in the COVID-19 pandemic. Naturally
occurring plants are source of wide variety of
Phytoconstituents. Tribulus terrestris, Withania somnifera,
Curcuma longa, Ocimum sanctum, Phyllanthus emblica are
primarily observed as effective against COVID-19. Moreover,
In-vitro and In-vivo studies require to-identify efficacy of
Herbal medicine. However, Combination therapies of
Allopathy and Herbal medicines lead towards the Best
treatment options. Still many unknown Herbals medicines are
waiting for their Identification and Purification and
pharmaceutical evaluation.
References
1. WHO | Herbal medicine research and global health: an
ethical analysis
https://www.who.int/bulletin/volumes/86/8/07-
042820/en/
2. HW. Pure and Applied Chemistry Natural products
chemistry and phytomedicine in the 21st century: New
developments and challenges. Pure and Applied
Chemistry, 2009, 77(1).
3. MoHFW Home. Retrieved 18 April, 2020, from
https://www.mohfw.gov.in/
4. World Health Organization. Monitored emergency use of
unregistered and experimental interventions (MEURI),
http://www.who.int/ethics/publications/infectious-
disease-outbreaks/en/
~ 1223 ~
Journal of Pharmacognosy and Phytochemistry http://www.phytojournal.com
5. Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y.
Analysis of therapeutic targets for SARS-CoV-2 and
discovery of potential drugs by computational methods,
2020.
6. Hastantram M, Ramaiah S. Molecular docking analysis
of selected natural products from plants for inhibition of
SARS-CoV-2 main protease. CURRENT Science.
2020; 118(7):1087-1092. Doi: 10.18520/cs/v118/i7/1087-
1092
7. Song YH, Kim DW, Curtis-Long MJ et al. Papain-like
protease (PLpro) inhibitory effects of cinnamic amides
from Tribulus terrestris fruits. Biol Pharm Bull. 2014;
37(6):10211028. doi:10.1248/bpb.b14-00026
8. Dwivedi D, Thanwar M. study of phytochemical active
compounds in extract of Withania somnifera. Rasāyan
Journal. 2015; 8(4):522-526.
9. Mahesh B. 'Antimicrobial Activity of Some Important
Medicinal Plant Against Plant and Human
Pathogens', World Journal of Agricultural
Sciences, 4:839-843
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1
.441.9036&rep=rep1&type=pdf (Accessed: 4th
september 2008).
10. Patwardhan B, Chavan-Gautam P, Gautam M, Tillu G,
Chopra A. Ayurveda rasayana in prophylaxis of COVID-
19, Current Science. 2020; 118:1-3.
11. Chandel V, Raj S, Rathi B. In silico Identification of
Potent COVID-19 Main Protease Inhibitors from FDA
Approved Antiviral Compounds and Active
Phytochemicals through Molecular Docking: A Drug
Repurposing Approach. Preprint, 1. DOI:
10.20944/preprints202003.0349.v1
12. Maurya D, Sharma D. Evaluation of Traditional
Ayurvedic Preparation for Prevention and Management
of the Novel Coronavirus (SARS-CoV-2) Using
Molecular Docking Approach. ChemRxiv. Preprint.
https://doi.org/10.26434/chemrxiv.12110214.v1
13. Dosoky N, Setzer W. Chemical Composition and
Biological Activities of Essential Oils of Curcuma
Species. Nutrients. 2018; 10:1196.
14. Khaerunnisa S, Kurniawan H. Potential Inhibitor of
COVID-19 Main Protease (Mpro) from Several
Medicinal Plant Compounds by Molecular Docking
Study, 2020.
http://www.lavierebelle.org/IMG/pdf/2020_potential_inh
ibitor_of_covid-
19_main_protease_from_several_medicinal_plant_comp
ounds.pdf
15. Gonzalez-Paz LA, Lossada CA, Moncayo LS.
Theoretical Molecular Docking Study of the Structural
Disruption of the Viral 3CL-Protease of COVID19
Induced by Binding of Capsaicin, Piperine and Curcumin
Part 1: A Comparative Study with Chloroquine and
Hydrochloroquine Two Anti-malaric Drugs. Research
Square; 2020. DOI: 10.21203/rs.3.rs-21206/v1.
16. Adem S, Eyupoglu V, Sarfraz I, Rasul A, Ali M.
Identification of Potent COVID-19 Main Protease (Mpro)
Inhibitors from Natural Polyphenols: An in Silico
Strategy Unveils a Hope against Corona. Preprints, 2020.
(doi: 10.20944/preprints202003.0333.v1).
17. Srivastava A, Singh D. Destabilizing the Structural
Integrity of SARS-CoV2 Receptor Proteins by Curcumin
Along with Hydroxychloroquine: An Insilco Approach
for a Combination Therapy. Chem Rxiv. Preprint.
https://doi.org/10.26434/chemrxiv.12090438.v1
18. Rane J, Chatterjee A. Targeting SARS-CoV-2 Spike
Protein of COVID-19 with Naturally Occurring
Phytochemicals: An in Silco Study for Drug
Development. Chemrxiv, 2020.
19. Varshney K, Varshney M, Nath B. Molecular Modeling
of Isolated Phytochemicals from Ocimum sanctum
Towards Exploring Potential Inhibitors of SARS
Coronavirus Main Protease and Papain-Like Protease to
Treat COVID-19 (March 14, 2020). Available at
SSRN: https://ssrn.com/abstract=3554371
20. Goothy S, Goothy S, Choudhary A, Potey G,
Chakraborty H, Kumar A et al. Ayurveda’s Holistic
Lifestyle Approach for the Management of Coronavirus
disease (COVID-19): Possible Role of
Tulsi. International Journal of Research in
Pharmaceutical Sciences. 11, SPL1 (Mar. 2020), 16-18.
DOI: https://doi.org/10.26452/ijrps.v11iSPL1.1976
21. Mondal S, Varma S, Bamola VD, Naik SN, Mirdha BR,
Padhi MM et al. Double-blinded randomized controlled
trial for immunomodulatory effects of Tulsi (Ocimum
sanctum Linn.) leaf extract on healthy volunteers, Journal
of Ethnopharmacology. 2011; 136(3):452456.
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