Pineapple, tea tree oil, Ginkgo biloba ‘cure’ for COVID-19

•Natural products in fruit peels have significant benefits for human health, researchers find
Scientists have demonstrated how extracts of pineapple, tea tree oil and Ginkgo biloba could be used to prevent and treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19.

In a recent study posted to the bioRxiv preprint server, scientists demonstrated that the pineapple-derived jacalin-related lectin (AcmJRL/AnLec) could be an anti- SARS-CoV-2 agent.

With approximately 529 million global SARS-CoV-2 cases identified to date, the current COVID-19 pandemic has emerged as one of the substantially challenging global health risks. Complementary to COVID-19 vaccines, innovative medications have been the topic of studies and development. SARS-CoV-2’s highly glycosylated spike (S) protein is a primary focus for antiviral medicines since it aids in infection.

The AcmJRL is found in substantial amounts in the drug bromelain and is known to attach mannosides. Further, an Ananas comosus (pineapple) stem extract, bromelain, is an authorised fibrinolytic, anti-inflammatory, and anti-edematous agent used to treat trauma-triggered swelling.

In the present work, the scientists ascribed the ligand selectivity of AcmJRL using glycan array assessment, characterized its contact with carbohydrates, and confirmed high-mannose glycans as AcmJRL’s favored ligands. The AcmJRL’s ligand selectivity was elucidated using two glycan arrays, Semiotik and Consortium for Functional Glycomics (CFG) glycan arrays. In addition, the engagement of AcmJRL with carbohydrates was evaluated in a competitive binding assessment. The authors evaluated the attachment of AcmJRL to recombinantly generated S protein and its derived receptor-binding domain (RBD) because the SARS-CoV-2 S protein was found previously to include a large proportion of high-mannose N-glycans.

The mannophilic lectin AcmJRL was extracted using affinity chromatography from a mannosylated stationary phase containing bromelain based on Azarkan et al. documented method. Before purification, bromelain’s soluble protein portion was derived by aqueous extraction in the context of S-methyl methanethiosulfonate to suppress the high proteolytic function of bromelain. Mass spectrometry (MS) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to validate the identity of the extracted protein. The team also employed dynamic light scattering (DLS) to calculate AcmJRL’s hydrodynamic diameter in the buffered solution.

The study results reported that AcmJRL possesses carbohydrates such as glucooligosaccharides and glucose, which could react with primary protein amines to generate Schiff-bases, followed by a permanent Amadori rearrangement to a stable alpha-amino ketone matching to advanced glycation end-products. An increase in mass (162 Da) was seen in the MS spectra following this glycation. The existence of two +324 Da and +162 Da signals indicates that this interaction occurred two times on a maltose disaccharide reacted or the protein.

The authors discovered that the low µM attaching of AcmJRL and SARS-CoV-2 S protein was carbohydrate-reliant and might be hindered by the addition of mannotriose. Furthermore, AcmJRL decreased the S RBD’s tight binding affinity for the human angiotensin-converting enzyme 2 (ACE2) receptor. As a result, bromelain and its component AcmJRL could be used as a new antiviral medication to neutralize SARS-CoV-2 after viral exposure.

The researchers concluded: “Overall, in the present study, the researchers illustrated that the AcmJRL attaches the SARS-CoV-2 S protein in a carbohydrate-dependent manner with a low micromolar Kd, implying that it might be a robust SARS-CoV-2 neutralizing proxy.”

Also, in a recent study published in the journal Molecules, researchers assessed the probable efficacy of tea tree oil (TTO) as a natural disinfectant against SARS-CoV-2 using the human coronavirus OC43 (HCoV-OC43) and feline coronavirus (FCoVII) as surrogate models.

SARS-CoV-2 can be transmitted in air or by contact with contaminated surfaces; therefore, effective disinfectants are essential to minimize exposure to SARS-CoV-2. Melaleuca alternifolia or TTO has been reported to have antiviral, antibacterial, and antifungal properties. It has been proposed that TTO can inhibit SARS-CoV-2 entry and influence the structural dynamics of the SARS-CoV-2 membrane and envelope constituents.

In the present study, researchers evaluated whether TTO could be potentially used as an effective disinfectant to limit SARS-CoV-2 contamination by assessing TTO efficacy using FCoVII and HCoV-OC43 as surrogate models.

The researchers concluded: “Overall, the study findings showed that TTO could be a potential disinfectant to limit SARS-CoV-2 transmission, based on TTO virucidal activity against FCoVII and HCoV-OC43 and alterations in the physical properties and structural organisation of the SARS-CoV-2 envelope.”

Also, in a recent study published in the journal Archiv der Pharmazie, researchers explored the effectiveness of Ginkgo biloba L. folium extract (EGb) in the management of coronavirus disease 2019 (COVID-19) severity.

COVID-19 is associated with several inflammatory disorders as well as the manifestation of oxidative stress in severe cases. Therefore, the development of therapeutic approaches against SARS-CoV-2 that target inflammation and oxidation can help alleviate COVID-19 complications.

Various studies have highlighted the broad‐spectrum antiviral activity of EGb and its impact on viral life cycle stages, such as viral binding, viral entry, expression of proteins, as well as assembly and release of proteins. This antiviral activity is mainly observed under the cytotoxic threshold. EGb is also known to have an inhibitory effect against influenza A and B viruses via disruption of the hemagglutinin (HA) to the host cells.

In the present study, the team noted that the transmissibility of the influenza A virus depends on the interactions between HA and neuraminidase (NA) with sialic acid present in the cell surface receptor. Ginkgetin, a natural biflavone isolated from GB, can effectively block the sialidase activity of the influenza virus, thus preventing viral adsorption on the host’s cell surface. Furthermore, EGb has been found to have a substantial antiviral effect against the H3N2 influenza virus as well as the hepatitis B virus.

The antiviral effect of GB is reported to be due to the disruption of viral fusion and the protective effect induced by GB on the host cells by improving its stability and reducing its permeability. Furthermore, studies showed that isorhamnetin, a flavonoid present in EGb, can inhibit NA and HA found in the H1N1 virus. This flavonoid also reduced autophagy induced by a viral infection, production of reactive oxygen species, and the phosphorylation of mitogen-activated protein kinase.

EGb and its components have also displayed anti-inflammatory effects via the inhibition of proinflammatory cytokines and the activation of anti-inflammatory cytokines. Various studies have noted that biflavones present in EGb, such as ginkgetin, significantly reduce the abnormal expression of Akt and p38 pathways in the basal epithelial cells. Biflavones also suppressed the expression of messenger ribonucleic acid (mRNA) of respiratory tract mucin, which could lead to mucociliary clearance failure.

EGb was also found to reduce the inflammation of the airway in asthmatic patients by decreasing the infiltration of the inflammatory cells, such as lymphocytes and eosinophils. It also suppressed the activity of protein kinase alpha (PKC‐α) of lymphocytes, thus preventing the secretion of interleukin 5 (IL-5) in the epithelial cells of the respiratory system. Additionally, a diterpene trilactone of GB called ginkgolide B also reduced the inflammatory reactions incident in the airway of patients who have asthma by reducing the secretion of platelet-activating factor (PAF).

The researchers concluded: “Overall, the study findings showed that GB preparations could serve as effective potential candidates in the management of COVID-19 and its disease severity. The researchers believe that further clinical trial studies could verify the effectiveness of EGb against COVID-19 disease progression.”

Meanwhile, a recent study published in Current Issues in Molecular Biology reviewed the potential biological applications of fruit peel extracts.

The European Union (EU) produces around 89 million tons of food waste yearly. The processing of fruits and vegetables alone results in 25 per cent to 30 per cent wastage of the total product. Although regarded as common waste products, seeds, rinds, and peels contain bioactive molecules like enzymes, oils, carotenoids, vitamins, and polyphenols.

Fruit and vegetable wastes consist of secondary metabolites that have been explored for phenolics, dietary fibers, and other bioactive compounds. Research suggests that essential nutrients and phytochemicals are abundant in fruit peels and seeds. For instance, the skin of grapes, lemons, avocados, and seeds of mangoes and jackfruits contain 15 per cent higher phenolics than the pulp.

In the present review, researchers discussed the biological compounds present in fruit peel extracts and their potential applications. Citrus peels contain bioactive compounds and have been conventionally used in some regions to treat cough, muscle pain, digestive problems, and skin inflammation. The peels of Citrus unshiu and C. reticulata are used as crude drugs in Japan as ‘Chimpi.’

Several coumarins have been isolated from the fruit peels of C. hystrix. Some coumarins (isoimperatorin, bergomottin, and oxypeucedanin) inhibit butyrylcholinesterase at varying half-maximal inhibitory concentrations (IC50). Other coumarins (example, oxypeucedanin hydrate) from the same plant have been implicated in the inhibition of inducible nitric oxide synthase (iNOS) synthesis in mouse RAW264.7 cells.

Fruit peels of Elaeagnus rhamnoides contain quinone(s), musizin, caulilexin C, and nor-sesquiterpene. Nor-sesquiterpene has been demonstrated to exert antiviral activity on herpes simplex virus 2 (HSV-2) in a virus reduction yield assay. Musizin, a derivative of naphthalene, was also found to be anti-HSV-2, albeit it was less potent. Pomegranate peels consist of punicagranine, a pyrrolizine alkaloid with anti-inflammatory effects. Besides, this alkaloid is non-cytotoxic to RAW264.7 cells. The polyphenol-rich fraction of Annona crassiflora fruit peels has antioxidant effects that can have potential clinical applications in diabetes treatment.

Steroidal alkaloids such as solamargine, solasodine, and solasonine have been detected in the fruit peels of Solanum melongena, which were cytotoxic to cancer cell lines such as HCT116, HepG2, HEp2, HeLa, and MCF7. Carbazole alkaloids such as claulansine K, claulansine J, carbazole-3-carboxylic acid, etc., were found in Clausena lansium peels. Claulansine K and clausenamide have been reported to inhibit α-glucosidase, whereas claulansine J showed moderate antibacterial effect against Streptococcus aureus.

Ataluntum present in Atalantia monophylla fruit peels was a potent cytotoxic compound for cholangiocarcinoma cells, with a 4.7-fold greater activity than the standard ellipticine. Other benzoyl tyramines from A. monophylla displayed cytotoxicity towards HeLa, HCT116, and MCF-7 cell lines. One study extracted flavones from Wisteria floribunda fruit peels and found several promising candidates for the inhibition of platelet-derived growth factor (PDGF)-induced proliferation of vascular smooth muscle cells (VSMCs).

Hesperidin present in C. sinensis and C. reticulata reportedly showed potent anti-inflammatory, antimicrobial, anti-carcinogenic, and antioxidant effects. Besides, hesperidin has also been used as a supplemental dietary product since its deficiency leads to weakness, aches, and nocturnal leg cramps. Polymethoxy flavones from the peels of Japanese citrus fruit, ‘hebesu,’ showed potent anti-neuro-inflammatory effects by inhibiting the expression of interleukin (IL)-1β.

Nobiletin is found in the fruit peels of several Citrus spp. and research has shown its anti-antioxidant, anti-inflammatory, and anti-tumor activity. Another study reported the inhibition of nuclear factor kappa -B (NF-κB) by nobiletin in mice models. Furthermore, in vivo studies reported the protective effects of nobiletin against different cancers.

Lignans such as syringaresinol and (–)-pinoresinol extracted from W. floribunda fruit peels inhibited PDGF-induced VSMC proliferation. Sesamin and sesamolin in the fruit peels of Strychnos nuxblanda demonstrated inhibition of α-glucosidase. Besides, W. floribunda fruit peels contain steroids like β-sitosterol and β-sitosterol glucopyranoside that inhibit VSMC proliferation. Pepstatin A, a peptide in the pomegranate peels, is an inhibitor of aspartic proteases.

Various countries have directed food industries to ensure low food wastage. As such, bioactive compounds like antimicrobials and antioxidants have been introduced as feasible solutions to enhance the shelf life of food products. A range of natural products present in fruit peels has antimicrobial, cytotoxic, and antioxidant properties. Using fruit peels, as sources of biologically active molecules, could be viable in preventing spoilage bacteria (Pseudomonas) and food poisoning caused by Staphylococcus aureus.

Edible coatings are thin layers on food surfaces that improve shelf life and help retain food characteristics and functionality. One research team synthesised an apple peel-based coating for beef patties. They revealed that the application of the edible film inhibited lipid oxidation and suppressed the growth of tested microbes.

Mounting evidence indicates the improvement of the shelf life of different food products (cupcakes, shrimps, strawberries, and tofu) by coating them with edible films derived from fruit peels. Interestingly, some studies have noted that adding powdered fruit peels to probiotic yogurts enhanced the growth of Lactobacillus spp.

The researchers wrote: Fruit peels, which represent a significant portion of industrial food by-products, have not been utilised as valuable resources. The authors of this study have described numerous biological compounds in fruit peels and reported their potential applications. Although generally considered an unhealthy and undesired by-product, the wide range of natural products in fruit peels, including peptides, steroids, alkaloids, and flavones, among others, could have significant benefits for human health.