Inhalation and topical use of a formulation containing cyclodextrin, quercetin and zinc, to mitigate infection by enveloped viruses, such as hiv and sars-cov-2

Abstract

The invention provides the use of a formulation containing cyclodextrine, quercetin and zinc at appropriate concentrations to mitigate infections by enveloped viruses, such as COVID-19 virus (SARS-CoV-2), influenza and HIV. While the different forms of cyclodextrin prevent the entry of coated viruses into host cells by extracting and sequestering cholesterol molecules at the virus envelope and at the host cell plasma membrane, the natural plant-based ionophore quercetin in the formulation enables cellular entry of zinc, inhibiting viral replication by altering polymerase activity in the host cell. SUBSTANCE: This formulation is adapted for both surface use and introduction to a subject by dispersal, utilizing the known methods of measured nasal sprays or inhalers, wet wipes and medicated masks. The formulation is introduced in the form of an aqueous phosphate buffered saline pH 7.5 solution, containing 0.01% benzylkonium chloride as preservative and different concentrations of the active ingredients: 1-5% cyclodextrin; the flavonoid quercetin, a naturally occurring zinc ionophore at a concentration of 8 μg/ml; and 1 mg/ml zinc chloride. Depending on requirement, pH 2.5 citrate buffered aqueous will also be used, where the low pH serves as a preservative and a solvent for cyclodextrin. The active ingredient cyclodextrin (CD): is currently being used as an excipient in pharmaceutical products including in nasal sprays. The U.S. Food and Drug Administration (FDA) has approved the use of CDs since 2001. CDs were first employed in the the food industry in the 1970s, and since they have been used as food additives for carrying food-related lipophiles such as vitamins, aromas and colorants. The first pharmaceutical patent related to CDs and pharmaceutical applicability, was made in 1953 to serve as a complexing agents. Pharmaceutical products containing CDs comprise nasal spray, oral solutions, solid dosage forms, ocular and dermal formulations, suppositories, and parenteral solutions. Currently, more than 40 pharmaceutical products containing CDs are available in the market worldwide, and the vast majority of them utilize βCD and its derivatives having higher water solubility such as HPβCD, MβCD, and SBEβCD. Most of the βCD are also approved by the European Medical Agency for all human administration pathways. The active ingredients zinc and quercetin: Zinc is an essential trace element supporting growth, development and immune health. Zinc is also known to protect against viruses by inhibiting RNA binding, RNA synthesis, viral polyprotein cleavage, viral replication, and viral protease enzyme inactivation. Zinc however, needs to enter the host cell to protect against the virus. Quercetin, a naturally occurring plant-based over the counter zinc ionophore, enables the cellular entry of zinc to protect host cells against the virus. Furthermore, quercetin has shown therapeutic effects against influenza virus. Additionally, in silico modelling of the interactions between the SARS-CoV-2 viral spike protein and the epithelial cell angiotensin converting enzyme-2 (ACE2) protein, has identified quercetin from a database of 8,000 small molecule candidates of known drugs, metabolites, and natural products, as one of the top 5 most potent compounds for binding to the interface site, and disrupt initiation of viral infection.

Dependencies are inferred from the claim text.