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Bioflavonoid Spray Efficacy Against Respiratory Viruses

July 9, 2021
by Zeeshan Sheikh, Dip.Dh, BDS, MSc, PhD; Henriette Lerner, DMD, DICOI


COVID-19 has raised new concerns about respiratory viral infections (RVI). This virus can reproduce within the cells that line the human respiratory tract and the resulting infections cause respiratory issues and may infect multiple other sites. At this time, there are more than 200 known viral strains that cause respiratory infection, including the coronavirus, influenza virus, and human rhinovirus. Other viruses of interest include parainfluenza viruses, metapneumovirus, adenovirus, respiratory syncytial virus (RSV) and human enteroviruses (HEV).1

Coronavirus can cause symptoms ranging from the common cold to worldwide pandemics. Influenza viruses are categorized into types:

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A/B cause seasonal epidemics (flu)
A is also implicated with seasonal pandemics
C/D are generally mild and do not affect humans

Each category has multiple subtypes. Rhinovirus has 3 main species including A/B/C with more than 160 viral types causing the common cold.2-4

Respiratory viruses: exposure, adhesion, replication, and infection
Key Respiratory Viruses are transmitted via aerosols, respiratory droplets, and fomites. Factors known to increase the risk of infection include: proximity, ventilation, surface contact, and time of exposure. Thus, gathering areas without adequate ventilation, where distancing is not possible, increase infection risk. These include workplaces, grocery stores, shopping malls, restaurants, indoor gyms, schools, and airplanes. Indoor activities with significant aerosolization increase risk, and while outdoor activities offer ventilation, physical distancing is not always possible.

In the event of an exposure, the respiratory viruses must come in contact with oral or nasal mucosa of a new host to pose a risk of infection. While the mucosal epithelium offers a partial physical and innate immune barrier against viral infection, the virus can still attach and infect the individual.5 It is extremely important to emphasize that for an infection to occur, the respiratory viruses must gain access to the mucosa, attach, internalize, and replicate within the host.

A novel protection strategy is to break the chain of infection by neutralizing the virus prior to adhesion and penetration of the host cell, either by a virus-encapsulating barrier, and/or via direct neutralization. Both ultimately prevent infection and disease.

Prevention of respiratory virus infection
The current challenge is two-fold: to reduce risk for COVID-19 and to develop multiple strategies that reduce the risk associated with new viruses with the potential to cause another pandemic crisis. COVID-19 occurred a full 100 years after the Spanish Flu (H1N1), but the next worldwide pandemic may present sooner. Current approaches for minimizing transmission are based on three common strategies:

  • Routine and widespread use of personal protection equipment (PPE), including masks, to create a physical barrier to transmission.6
  • Frequent and thorough disinfection of hands, surfaces and fomites to mechanically remove and chemically inactivate shed virus particles and prevent their translocation to new hosts.7
  • Delivery of aerosolized therapeutics to the mucosal microenvironment to dampen an aggressive immune response in respiratory infections, thereby improving clinical outcomes.8

It is very desirable to prevent viruses that have entered the human body via the nasal and oral passages from gaining access to the mucosal layers, adhering, and causing infection. One practical
approach is an oral spray that targets the mucosa in the mouth and throat to create an additional barrier that protects the host from viruses. The ideal spray must be safe and use Generally Recognized as Safe ingredients (GRAS) and have a pleasant taste and sensation. Additionally, it must be easy to use, acceptable for all ages, and must provide rapid onset to target specific situations. Further desirable properties include: vegetarian compatibility, sustainability, non-GMO sourcing, and no banned substance ingredients.

Flavobac and mucosal viral barriers
Flavobac is a plant-based, patented combination of specific water-soluble bioflavonoid molecules with known anti-microbial and anti-viral activity.9 The pharmacological effects of Flavonoids are linked to their antioxidant and free-radical scavenging activity in addition to their interaction with enzymes, adenosine receptors and bio-membranes.10 Flavonoids have also been shown to possess anti-viral activity against influenza viruses HSV-1, HSV-2 and the rotavirus.9

There are several products designed to assist in preventing the onset of infection caused by rhinovirus/coronavirus/influenza virus by creating a physical barrier to viral and bacterial adhesion at the nasal and throat mucosal membranes. Oral Science International (Brossard, QC) has a unique formulation, Cold & Flu GuardTM, (Fig. 1) that unites bioflavonoids with the mucosal barrier. Glycerin and hyaluronic acid components form a barrier/film over the mucous membrane, and act as a delivery method for the bioflavonoids and menthol.

Fig. 1

Cold & Flu Guard combines bioflavonoids with an effective mucosal barrier.

Cold & Flu Guard combines bioflavonoids with an effective mucosal barrier.

Flavobac Efficacy vs Respiratory Viruses
In vitro efficacy studies of Flavobac aqueous solutions have demonstrated concentration-dependent activity against a range of bacterial, fungal and protozoal pathogens.11 Antiviral studies have confirmed activity against various viruses.12-14 Retroscreen Virology Laboratories (now hVIVO, London, United Kingdom) and Biobest Laboratories (Edinburgh, United Kingdom) have independently demonstrated that Flavobac formulations are efficacious in the inactivation of two different subtypes of Influenza A: H5N1 (Bird Flu) and H1N1 (Swine Flu).13,15 In 2004, Retroscreen Virology Ltd., Barts and The London Queen Mary’s School of Medicine and Dentistry, evaluated the viricidal activity of Flavobac against Urbani SARS virus, Influenza A virus, Human Rhinovirus and HIV. The results demonstrated significant viricidal activity against all the viruses at all concentrations and time-points.14

The first anti-SARS-CoV-2 evaluation of an oral spray formulation containing Flavobac as the sole active ingredient (developed specifically for routine intranasal or intraoral use) was Reported in March 2021 by the Institute for Antiviral Research (IAR) at Utah State University (Logan, UT) [*data pending publication]. The IAR employs recognized scientists to identify antiviral agents and vaccines against a wide range of human pathogenic viruses and has participated in the pre-clinical development of numerous FDA-approved antiviral compounds.

Test compounds: Nasal antiseptic
solutions and oral rinse antiseptic solutions (Fig. 2) consisting of aqueous Flavobac BCL concentrate as the sole active ingredient and OSI2021003 oropharyngeal spray solution and other natural ingredients were supplied by Oral Science International (Brossard, Canada).

Fig. 2

Nasal antiseptic spray solutions and oral antiseptic spray solutions.

Nasal antiseptic spray solutions and oral antiseptic spray solutions.

Results: Flavobac aqueous solution reduced SARS-CoV-2 titer below the limits of detection at all concentrations tested. (Table 1) These results generate dose optimization and guide product dosage and concentrations.

Table 1

After incubation with Flavobac commercial solutions OSI-20210203A and OSI-20210203B, SARS-CoV-2 virus titers and LRV were reduced below the limits of detection (LRV>3.0) (Table 2). Each Flavobac containing solution evaluated was effective at reducing >3 log10 CCID50 infectious virus, from 4.7 log10 CCID50/0.1 mL to 1.7 log10 CCID50/0.1 mL or less. (Table 2) This represents a >99.9% efficacy of viral reduction.

Table 2

Relevance
The challenge in developing oral and nasal sprays is to create effective topical preparations that are safe and have the required efficacy against respiratory viruses. Ethanol >70%, for example, is known to be an effective viricidal agent but cannot be used safely in the nose. Flavobac solutions and formulations have been shown to be effective against a variety of viral strains and are non-toxic (GRAS status in the USA via the FDA).

Given their efficacy and safety profile, Flavobac oral and nasal spray products such as Cold & Flu GuardTM and Flavobac Health GuardTM, can be considered as a supplementary layer of protection in addition to face masks in combatting respiratory viruses. (Fig. 3) This is particularly beneficial and important for:

  • High aerosolization situations
  • Individuals at higher risk of respiratory viral complications
  • Those not yet vaccinated
  • Children
  • Everyone gathering where appropriate distancing is not possible.

Fig. 3

Nasal and oral sprays function as supplementary layers of protection (in addition to face masks) to short circuit cold and flu viruses.

Nasal and oral sprays function as supplementary layers of protection (in addition to face masks) to short circuit cold and flu viruses.

Oral Health welcomes this original article.

Resources

https://www.cdc.gov/coronavirus/types.html
https://www.cdc.gov/flu/about/viruses/types.htm
https://www.lung.org/

* Pending publication: Efficacy of FLAVOBAC Nasal and Oral Preparations Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), A. Barbour, M. Mendenhall, G. Darlington MD, M. Glogauer (Pending Publication in medRxiv).

References

  1. Mäkelä, M.J., et al., Viruses and bacteria in the etiology of the common cold. 1998. 36(2): 539-542.
  2. Couch, R.B.J.e.L., Rhinoviruses. 2001.
  3. Peiris, J.J.M.m., Coronaviruses. 2012: 587.
  4. Zhang, Y., et al., New understanding of the damage of SARS-CoV-2 infection outside the respiratory system. 2020: 110195.
  5. Gwaltney Jr, J.M.J.T.A.j.o.m., Clinical significance and pathogenesis of viral respiratory infections. 2002. 112(6): 13-18.
  6. Organization, W.H., Rational use of personal protective equipment (PPE) for coronavirus disease (COVID-19): interim guidance, 19 March 2020. 2020, World Health Organization.
  7. Cohen, M.S. and L. Corey, Combination prevention for COVID-19. 2020, American Association for the Advancement of Science.
  8. Oslund, K.L. and N.J.F.v. Baumgarth, Influenza-induced innate immunity: regulators of viral replication, respiratory tract pathology & adaptive immunity. 2011. 6(8): 951-962.
  9. Bylka, W., I. Matlawska, and N.J.J. Pilewski, Natural flavonoids as antimicrobial agents. 2004. 7(2): 24-31.
  10. Harborne, J.B. and C.A.J.P. Williams, Advances in flavonoid research since 1992. 2000. 55(6): 481-504.
  11. Hooper, S.J., et al., Antimicrobial activity of Citrox® bioflavonoid preparations against oral microorganisms. 2011. 210(1): E22-E22.
  12. Lalani, S. and C.L.J.V. Poh, Flavonoids as antiviral agents for Enterovirus A71 (EV-A71). 2020. 12(2): 184.
  13. Reis, A.C.C., et al., Anti-Zika virus activity and chemical characterization by ultra-high performance liquid chromatography (UPLC-DAD-UV-MS) of ethanol extracts in Tecoma species. 2020. 20(1): 1-15.
  14. Zou, M., et al., Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection. 2020. 177:
    113962.
  15. Carrouel, F., et al., Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2. 2020: 0022034520967933.

About the Authors

Dr. Sheikh trained as a dental clinician and a biomaterial scientist, has earned BDS, MSc and PhD degrees at Baqai Dental College, Queen Mary, University of London and McGill, and completed two Post-Doctoral Fellowships, University of Toronto and Mt. Sinai Hospital. A Periodontics & Implant Surgery Resident at Dalhousie, his research focuses on developing novel bone grafting biomaterial options and maxillofacial regenerative applications.

Dr. Henriette Lerner, graduate of Temeschburg University (DMD) and Carol Davila University, (Postgrad. Prog. in Oral Surgery) is Director, HL Dental Clinic & Academy in Baden-Baden, Germany, and Tutor in the Esthetic Dentistry Master Program at Johann Wolfgang Goethe University, Frankfurt-am-Main.


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