Bee Venom—A Potential Complementary Medicine Candidate for SARS-CoV-2 Infections

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by severe cytokine storm syndrome following inflammation. SARS-CoV-2 directly interacts with angiotensin-converting enzyme 2 (ACE-2) receptors in the human body. Complementary therapies that impact on expression of IgE and IgG antibodies, including administration of bee venom (BV), have efficacy in the management of arthritis, and Parkinson's disease. A recent epidemiological study in China showed that local beekeepers have a level of immunity against SARS-CoV-2 with and without previous exposure to virus. BV anti-inflammatory properties are associated with melittin and phospholipase A2 (PLA2), both of which show activity against enveloped and non-enveloped viruses, including H1N1 and HIV, with activity mediated through antagonist activity against interleukin-6 (IL-6), IL-8, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). Melittin is associated with the underexpression of proinflammatory cytokines, including nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinases (ERK1/2), and protein kinase Akt. BV therapy also involves group III secretory phospholipase A2 in the management of respiratory and neurological diseases. BV activation of the cellular and humoral immune systems should be explored for the application of complementary medicine for the management of SARS-CoV-2 infections. BV “vaccination” is used to immunize against cytomegalovirus and can suppress metastases through the PLA2 and phosphatidylinositol-(3,4)-bisphosphate pathways. That BV shows efficacy for HIV and H1NI offers opportunity as a candidate for complementary therapy for protection against SARS-CoV-2.

Cardiac biomarkers, cardiac injury, and comorbidities associated with severe illness and mortality in coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

“…There have been studies showing that the heart is susceptible to SARS‐Cov‐2 infections 89 . A further mechanism for explanations involves a cytokine storm, which is described as an excessive immune response towards SARS‐CoV‐2 infection 90,91 . Cytokines are essential to infection control, but when the immune system is deregulated including the imbalanced response of type 1 and type 2 T helper cells, a cytokine storm will be observed, resulting in an excessively elevated level of cytokines, such as C‐reactive protein interleukin 8 (IL‐8), IL‐10, procalcitonin, IL‐1b, and tumor necrosis factor‐α particularly IL‐6 coupled with tissue damage and multiple organ dysfunctions 92 …”

Gramicidin S and Melittin - Potential anti-viral therapeutic peptides to treat SARS-CoV-2 infection

“…Bee venom (BV) has immunosuppressive activity and is generally used in contemporary medicine to treat Multiple Sclerosis, Parkinson's disease, and arthritis. Bee venom activates foxP3-expressing cells, CD25 and CD4+ T cells, and thus modulates the IgE antibody ratio, resulting in a variety of allergic reactions to antigens [26]. This immunosuppressive activity was observed in Wuhan beekeepers against COVID-19 [26].Melittin is the main component of bee venom, and it active against both enveloped and non-enveloped viruses by activating the Toll-like receptors (TLRs) pathway, which reduces inflammatory cytokines like nuclear factor-kappa B (NF-kB), extracellular signal-regulated kinases (ERK1/2), and protein kinase Akt [26].…”

Repurposing of Sitagliptin- Melittin Optimized Nanoformula against SARS-CoV-2; Antiviral Screening and Molecular Docking Studies

“…In addition, the distinction between FOXP3-expressing cells in CD4 T cells and mature CD4 thymocytes was significantly enhanced by bee venom [ 34 ]. Notably, bee venom has been suggested to induce human regulatory T cell differentiation, which plays a prominent role in the immune response to SARS-CoV infection [ 34 , 35 ]. Further research is needed to explain whether or not the bee venom and its components can be utilized as a SARS-CoV-2 antiviral agent or as a COVID-19 immune system activator [ 35 ].…”

“…Notably, bee venom has been suggested to induce human regulatory T cell differentiation, which plays a prominent role in the immune response to SARS-CoV infection [ 34 , 35 ]. Further research is needed to explain whether or not the bee venom and its components can be utilized as a SARS-CoV-2 antiviral agent or as a COVID-19 immune system activator [ 35 ]. As a matter of fact, chemical strategies such as conjugation with polyethylene glycol (PEGylation), truncation, and peptide synthesis with dextrogenous (d-)amino acids may be able to minimize the toxicity of MEL [ 36 , 37 ].…”