Plant Extracts and SARS-CoV-2: Research and Applications
Abstract
:1. Origin and Evolution of Pathogenic Coronaviruses
2. Morphology and Infection Route of Coronavirus
3. Antiviral Therapies and Vaccine Strategies
Rug Name | Main Function | Permission Sought | Reference |
---|---|---|---|
Veklury® (remdesivir) | After conversion to remdesivir monophosphate, this compound stalls viral RNA-polymerase | EU and US | [16] |
Olumiant® (baricitinib) | This tyrosine kinase regulates the immune response of the body, avoiding a cytokine storm | EU and US | [17] |
Kineret® (anakinra) | This recombinant interleukin (IL)-1 receptor antagonist helps control the hyperinflammatory syndrome of COVID-19 | EU | [18] |
RoActemra® Actemra® (tocilizumab) | Recombinant humanized monoclonal antibody that prevents the binding of IL-6 to its receptor, inhibiting the inflammatory cascade | EU and FDA | [19] |
Bamlanivimab and etesevimab | Neutralizing monoclonal antibodies that target the spike glycoprotein of the virus rendering it impossible to enter the host cell | EU and US | [20] |
Regdanvimab | Monoclonal antibodies which also reduce viral entry in host cells | EU | [21] |
REGN-COV-2® Casirivimab/imdevimab | Monoclonal antibodies that also target the spike glycoprotein | US | [22] |
Sotrovimab® (VIR-7831) | Monoclonal antibodies that reduce viral entry into host cells and help clear infected cells | EU and US | [23] |
4. Plant Metabolites: Debunking Misconceptions
5. Antiviral Activity of Natural Sources
Phenolic Compounds/Class | Type of Compound/Extract | Extraction Methods | Virus | Reference |
---|---|---|---|---|
Phenolic glucosides | Ethanol extract from the leaves of the poplar tree cultivar Beaupré (Populus trichocarpa) | Ethanol extraction of the hot water-soluble portion followed by polyamide chromatography employing step-gradient elution with water and dilutions of ethanol | Poliomyelitis virusSemliki forest virus | [46] |
p-Quinone monooximes derived from 3-methoxyphenol - 8-hydroxyquinoline | Synthetic aromatic nitro compounds | Extract washed with brine, dried over magnesium sulfate and filtered. Filtrate evaporated to dryness under reduced pressure. i-AmNO2 added to a stirred solution of a phenol in DMF in the presence of K2CO3 at 0 °C under argon. Recrystallization of the crude product from an appropriate solvent gave a p-quinone monooxime | Herpes simplex virus type 1 (HSV-1) | [51] |
Alkyl-esters of gallic acid 3,4,5-trihydroxy derivatives of gallic acid 3,4,5-trimethoxy derivatives of gallic acid Catechin Epicatechin Quercetin Epigalocatechin | Commercial standard and lab synthesis | - | Rabies virus | [47] |
Apigenin Naringin Atropine Genistein Gallic acid Chlorogenic acid Quinic acid | Commercial standard | Compounds dissolved in dimethyl sulfoxide to prepare a final concentration of 256 μg/mL | Herpes simplex virus type 1 (HSV-1) Parainfluenza virus type 3 (PI-3) | [49] |
Apigenin Acacetin 7-O-[4′′′-O-acetyl-β-d-apiofuransyl-(1→3)]-β-d-xylopyranoside | Origanum vulgare L. plant extracted with 95% (v/v) ethanol | Air-dried plants percolated with 95% ethanol solution. Ethanol extract concentrated in vacuum to yield a residue, which was suspended in water and partitioned with petroleum ether and ethyl acetate, respectively | Herpes simplex virus type 1 (HSV-1) Respiratory syncytial virus (RSV) | [50] |
Kaempferol Kaempferol-7-O-glucoside | Hydromethanolic extracts (98%) from Securigera securidaca seeds | Dried seeds extracted methanol (98%) at 40 °C. The methanol extract was eluted with n-hexane: acetone and then with 100% methanol | HIV-1 | [48] |
Quercetin Kaempferol-3-O-(6″-O-E-p-coumaroyl)-β-d-glucopyranoside Mangiferin | Bombax ceiba L. Flowers extracted with 95% (v/v) ethanol | Extraction by reflux with 95% ethanol | Respiratory syncytial virus (RSV) | [52] |
Xanthopurpurin (1,3-dihydroxy-9,10-anthracenedione) Vanillic acid (4-hydroxy-3-methoxybenzoic acid) | Aqueous extract from Rubia cordifolia L. aerial parts | Plant aerial parts boiled in distilled water for 1 h, the aqueous solution collected and the residual part re-extracted several times | Rotavirus | [47] |
Catechin Gallic acid | Commercial standards | - | H1N1 Influenza virus | [55] |
Gallic acid Ellagic acid | Aqueous and organic-solvent extracts of Rhodiola rosea L. plant | Extracts dried in vacuum at 50 °C and dissolved in DMSO | Ebola virus | [1] |
Quercetin 3-glucoside | Hydromethanolic (70% methanol) and methanol (100%) extracts from Dianthus superbus L. leaves | Dried leaves extracted using 70% and 100% methanol | H1N1 Influenza | [53] |
Hibiscus acid Protocatechuic acid | Acidic hibiscus tea extract | Hibiscus tea powder soaked in ultrapure water at 24 °C for 24 h, repeating the process several times | H1N1 Influenza virus | [54] |
Phenolic Compounds/Class | Type of Extract | Extraction Methods | Concentration | Reference |
---|---|---|---|---|
Tetra-O-galloyl-beta-D-glucose (TGG) Luteolin | Hydroethanolic extract | Herbs extracted by maceration with 85% ethanol at room temperature for 2 weeks | 4.5 µM 83.4 µM | [59] |
Aloe emodin Hesperetin | Aqueous extract from Isatis indigotica roots | Plant roots extracted twice with 10 volumes of distilled boiling water for 1 h | 132 μM, 366 μM and 911.592 μM 60 μM, 8.3 μM and 2718 μM | [60] |
Saikosaponins (A, B2, C and D) | Commercial standards | Saikosaponins dissolved in DMSO and further diluted with RPMI 1640 medium | 25 µmmol | [70] |
A. emodin | Aqueous extract of the root tuber from Rheum officinale Baill. and Polygonum multiflorum Thunb. | Deionized water | IC50 values ranged from 1 to 10 μg/mL. | [61] |
Flavonoids from a Chinese multiherb remedy constituted by Herba Houttuyniae, Flos Chrysanthemi Indici, Herba Artemisiae Scopariae, Herba Eupatorii and Fructus Tsaoko | Hydroethanolic extract | Herb mixture extracted with 95% EtOH at room temperature | From the nine flavonoids with inhibitory effects, luteolin was the most potent with a CH50 (50% inhibitory concentration) of 0.19 mM | [71] |
n.a. | Hydroethanolic extracts of Rheum palmatum L. (ethanol (75%)) | Petroleum ether and chloroform, and ethyl acetate | Among the extracts, RH121 has the highest activity, with an IC50 of 13.76 μg/mL | [67] |
Tanshinones | Hydroethanolic extract (95%) of the dried roots of Salvia miltiorrhiza Bunge | The crude extract was filtered and evaporated under reduced pressure. The obtained residue was suspended with distilled water | IC50 value of 0.7µM | [65] |
Phlorotannins | Ethanol extract of brown alga Ecklonia cava Kjellman | Ethanol at room temperature | Of the nine phlorotannins tested, two eckol groups with a diphenyl ether linked dieckol showed the most potent SARS-CoV 3CLpro trans/cis-cleavage inhibitory effects; IC50 = 2.7 and 68.1 μM, respectively) | [62] |
Flavonoids (bavachinin, neobavaisoflavone, isobavachalcone, 4′-O-methylbavachalcone, psoralidin and corylifol A) | Fractionation of hydroethanolic extract from the seeds of Psoralea corylifolia L. | Ethanol, water and n-hexane | IC50 ranging between 4.2 and 38.4 µM | [68] |
Juglanin Kaempferol-3-O-α-rhamnopyranosyl(1→2) [α-rhamnopyranosyl(1→6)]-β-glucopyranoside | Kaempferol acylated glucosides were previously isolated from polar extracts from the leaves of the plant Quercus ilex L.; the kaempferol triglycoside was an isolate from Viola odorata L (decoction and infusion) | Cyclohexane, Et2O, MeOH and MeOH–H2O | The most effective one was the glycoside juglanin with an IC50 of 2.3 µM | [69,72] |
Alkylated chalcones | Hydroethanolic extract from the leaves of Angelica keiskei Ito | 95% ethanol for a week at room temperature | IC50 values of 11.4 (3CLpro) and 1.2 µM (PLpro) | [63] |
Broussochalcone B, Broussochalcone A, 4-hydroxyisolonchocarpin, Papyriflavonol A, 3′-(3-methylbut-2-enyl)-3′,4,7-trihydroxyflavane, Kazinol A, Kazinol B, Broussoflavan A, Kazinol F, Kazinol J | Ethanolic extracts from the roots of Broussonetia papyrifera (L.) Vent. | Ethanol at room temperature and evaporated using a rotary evaporator at temperatures below 45 °C to obtain the total extract. | Papyriflavonol A was the most potent inhibitor of PLpro with an IC50 of 3.7 μM. | [64] |
Epicatechin 5-O-beta-D-glucopyranoside-3-benzoate Neohesperidin Kaempferol-3,7-O-dirhamnoside (Kaempferitrin) Quercetin-3-O-neohesperidoside Oleic acid 3,4,5-Trimethoxyphenol Epicatechin Oxypeucedanin hydrate 3-Feruloylquinic acid Eriodictyol Apigenin Luteolin C-Methyl flavone β-amyrin Isovitexin-2″-O-rhamnoside | Methanolic extracts from Fragaria ananassa Duch. | 80% methanol at room temperature. | Strawberry methanolic extract showed the highest antiviral activity against SARS-CoV-2 with an IC50 value to 0.0062 µg/mL | [2] |
Sinapic acid | Ethanolic extract of broccoli (obtained from a local market) | 95% ethanol | Potent SARS CoV-2 inhibition with a half-maximal inhibitory concentration (IC50) value of 2.69 µg/mL | [73] |
Derivatives of luteolin, kaempferol, apigenin, isorhamnetin, myricetin, chrysoeriol, biochanin, isookanin and scutellarein | V. vinifera (var. Paulsen 1103) leaf extract | 75% (v/v) methanol/0.05% (v/v) trifluoroacetic acid | Leaf extract was able to inhibit both HSV-1 and SARS-CoV-2 replication in the early stages of infection by directly blocking the proteins enriched on the viral surface, at a very low concentration of 10 µg/mL | [74] |
TFC of sampled wild S. nigra was 9.57 ± 0.65 mg RE g−1 DW of plant material for berry extracts and 77.59 ± 10.23 mg RE g−1 DW of plant material for flower extracts. TPC of sampled wild S. nigra was 41.31 ± 9.44 mg gallic acid equivalent (GAE) g−1 DW for berry extracts and 451.72 ± 25.31 mg GAE g−1 DW for flower extracts | Ethanolic Extract of Sambucus nigra L. berry and flowers | 80 % ethanol at 60 °C | Concentration-dependent inhibition of ACE2-SARS-CoV2 S-protein RBD binding was demonstrated in vitro for elderberry fruits and flowers extracts (IC50 of 1.66 mg DW ml−1 and 0.532 mg DW ml−1, respectively) | [75] |
Caffeic acid, caftaric acid, chlorogenic acid, cichoric acid, cynarin, echinacoside | Echinacea purpurea (echinaforce) | 65% ethanol | 50 µg/mL inactivation of SARS-CoV1 and 2 | [76] |
Glyzyrrhizin | Glycyrrhiza glabra | Acquired compound | 300 mg/L | [77] |
Baicalein | Scutellaria baicalensis | 70% ethanol (crude extract of plant) and commercial baicalein | IC50 8.52 µg/mL (crude extract) and 0.39 µg/mL (baicalein) | [78] |
Epigallocatechin, genistein, sulforaphane, chlorogenic acid, resveratrol and quercetin | - | Acquired compounds | IC50—33.9 µg/mL (epigallocatechin) | [79] |
Whole plant extract | Taraxacum officinale | Aqueous extractions for 1 h | EC50—14.9 mg/mL | [80] |
6. Coronavirus Inhibition Assays
7. Future and Trends
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Vaccine | Type | Manufacturer | Approval |
---|---|---|---|
Approved | |||
Comirnaty | mRNA | Pfizer-BioNTech | EU and US |
Spikevax (former Moderna) | mRNA | Moderna | EU and US |
Vaxzevria (former AstraZeneca) | Modified adenovirus | AstraZeneca | EU |
Janssen | Modified adenovirus | Janssen | EU and US |
Novavax | Spike glycoprotein subunit | Novavax | EU and US |
Under Rolling Review | |||
Sanofi (Vidprevtyn) | Spike glycoprotein subunit | Sanofi-GSK | Sought in EU |
HIPRA Human Health | Spike glycoprotein subunit | HIPRA | Sought in the EU |
Valneva | Inactivated coronavirus | Valneva | Sought in the EU |
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Heleno, S.A.; Carocho, M.; Reis, F.S.; Pires, T.C.S.P.; Pintado, M.; Ferreira, I.C.F.R.; Barros, L. Plant Extracts and SARS-CoV-2: Research and Applications. Life 2023, 13, 386. https://doi.org/10.3390/life13020386
Heleno SA, Carocho M, Reis FS, Pires TCSP, Pintado M, Ferreira ICFR, Barros L. Plant Extracts and SARS-CoV-2: Research and Applications. Life. 2023; 13(2):386. https://doi.org/10.3390/life13020386
Chicago/Turabian StyleHeleno, Sandrina A., Marcio Carocho, Filipa S. Reis, Tânia C. S. P. Pires, Manuela Pintado, Isabel C. F. R. Ferreira, and Lillian Barros. 2023. "Plant Extracts and SARS-CoV-2: Research and Applications" Life 13, no. 2: 386. https://doi.org/10.3390/life13020386