Hydrogen Peroxide and Viruses

Hydrogen Peroxide and Viruses

Milton V. Marshall, PhD, DABT, RQAP-GLP, CCRP*

Significant evidence exists for the antiviral activity of hydrogen peroxide toward coronaviruses. The US
Environmental Protection Agency regulates disinfectants, and 0.5% hydrogen peroxide and other
products are registered as a disinfectant for human coronaviruses (EPA List N). Inactivation of SARS-CoV2 on surfaces can occur with a variety of biocidal agents, including hydrogen peroxide (Kampf et al.). The
FDA allows use of vaporized hydrogen peroxide for sterilizing respirators for reuse under the Emergency
Use Authorization Act.

Hydrogen peroxide kills SARS-CoV-2 on surfaces. It likely disrupts the viral envelope by interacting with
the spike protein or disrupting the envelope and attacking the viral RNA, either of which would prevent
the virus from replicating. In the presence of iron (Fe2+) or copper (Cu2+), the hydroxyl radical is
generated (Floyd, Zs-Nagy), which can form 8-oxoguanosine in the viral mRNA. The formation of 8-
oxoguanosine leads to incomplete translation of the viral genome (Dai; Sims et al.). RNA is more reactive
with reactive oxygen species than DNA (Hofer et al.).

Exposure to SARS-CoV-2 can occur via aerosolization (Bourouiba; Anfinrud et al., Lu et al., Santarpia et
al., Meselson). SARS-CoV-2 can be detected in saliva and sputum (Wang et al.; Han et al.; To et al.;
Sabino-Silva et al.). Salivary glands have ACE-2 receptors to which the SARS (SARS CoV-1) virus can
attach and enter the cells (Liu et al.). It is reasonable to assume that SARS-CoV-2 will also infect the
salivary gland cells that have ACE-2 receptors, in addition to cells with the ACE-2 receptor within the
respiratory tract (Liu). To decrease the risk of viral transmission, the American Dental Association (ADA)
recommends rinsing the mouth with 1.5% hydrogen peroxide prior to conducting procedures in a dental
office (ADA COVID-19 Center).

Dental team exposure can occur from a variety of processes, including direct transmission of viral
particles in saliva, by inhalation of droplets, and indirect transmission through contact with procedure
tools or surfaces in the examining room (Peng et al.). The likelihood of developing COVID-19 symptoms
and transmitting SARS-CoV-2 to additional patients would be reduced by preprocedural treatment with
hydrogen peroxide. Although it has not been tested in clinical trials against SARS-CoV-2, hydrogen
peroxide is recommended as a pre-procedural rinse (Peng et al.).

Hydrogen peroxide has a long history of use in dentistry and is considered safe for daily use at
concentrations up to 3% (Marshall et al. 1995). Patients rinsing with hydrogen peroxide should not
swallow the rinse; however, if they accidentally do swallow peroxide in a concentration of 3% or less, it
poses very little risk (21 CFR Part 356. [Docket No. 81N-033P]; Mahoney, et al.).

When used as a topical agent in the oral cavity, concerns have been raised regarding free oxygen
radicals. Any peroxide product will initiate the production of free radicals, but this is not necessarily
harmful. Peroxide is generally present in the human mouth. Active inflammatory cells, like pulmonary
alveolar macrophages, release peroxide in the lungs and it is carried into the mouth in exhaled breath
(Teng et al.; Olin et al.). In the oral cavity, the enzyme catalase breaks down hydrogen peroxide into
oxygen and water very quickly. Salivary peroxidase and glutathione provide additional protective
properties. Some products, like Perio Gel®, are also formulated with free radical trapping agents.

Humans make hydrogen peroxide in the liver (Chance et al.) and it is used by white blood cell for
phagocytosis. In the body, phagocytic cells release active oxygen species and use reactive oxygen
species internally to destroy phagocytized pathogens, including bacteria and viruses, as a normal part of
the host defense system against pathogens. In treatment for oral health, the oxidizing elements of
peroxide help debride bacterial cell walls. (Schaudinn et al.; Dunlap et al.) The oxygenating effects are
multiple but the most important for long-term gingival health is the modification of the
microenvironment of the periodontal pocket or sulcus so that healthy bacteria repopulate at the
expense of pathogens. This is possible when hydrogen peroxide gel is administered with a Perio Tray®
(Schaudinn et al.; Keller and Cochrane; Putt et al., 2012-2014). Against viral agents, the oxidizing
properties of hydrogen peroxide are the most important against viral agents.

Although the FDA has not approved any hydrogen peroxide product for treatment or prevention of
SARS-CoV-2, the preceding information provides compelling evidence for use of hydrogen peroxide in
patients who present for treatment in a dental office to protect dentists, hygienists, and dental
assistants from exposure to persons who may be infected with SARS-CoV-2 but are asymptomatic.
Hydrogen peroxide is more stable in the oral cavity when delivered as a gel in a tray, rather than rinsing
as a liquid or delivery without a tray (Marshall MV unpublished observations), including brushing with a
gel (Marshall et al. 2001).

In summary, hydrogen peroxide can inhibit virus replication through a number of different mechanisms
– altering the viral envelope, which can decrease binding of a virus to cells leading to reduced infectivity,
alteration of nucleic acids, leading to reduced protein synthesis, and alteration of viral and intracellular
proteins, leading to enzyme inactivation. On surfaces, levels of hydrogen peroxide as low as 0.5% are
effective in decontamination. In the presence of iron (Fe2+) or copper (Cu2+), hydrogen peroxide can
form the hydroxyl radical, which greatly increases potency as a decontaminant. Following the
recommendation of the ADA to rinse with 1.5% hydrogen peroxide prior to procedures, use of a delivery
tray to apply hydrogen peroxide gel will enable extended release of hydrogen peroxide, which should
provide a more effective pretreatment to avoid exposure to dental office personnel to SARS-CoV-2.

• _{Milton Marshall received a PhD from the University of Texas Health Science Center at Houston. His PhD dissertation was, “The
  mengovirus replicative form RNA: Properties and possible role in inhibition of host protein synthesis”. Mengovirus is in the family
  of picornaviruses in a subgroup called enteroviruses that includes poliovirus, and it has the same type of genetic material as SARSCoV-2, a positive strand of RNA that acts like a messenger RNA, which produces an enzyme that replicates the viral RNA in a duplex
  (double-stranded) form; these RNAs are further replicated and proteins are translated from the positive strand. SARS-CoV-2 is an
  enveloped virus that contains elements of the host cell in its envelope, along with the spike protein that attaches to
  acetylcholinesterase-2 (ACE-2) receptors to gain entry into susceptible cells. Mengovirus and other picornaviruses have a capsid
  rather than an envelope. Both viruses must gain entry into a cell for replication to occur.
  Milton Marshall has also worked on hydrogen peroxide-containing or -generating products to ensure their safety, presenting safety
  data on hydrogen peroxide to the FDA (Final Monograph for Over-the-Counter Drug Products for the Reduction or Prevention of
  Dental Plaque and Gingivitis, Docket No. 81 N-033P). He was also involved in establishing safety testing recommendations for
  peroxide-containing or -generating products that were developed by the ADA (ADA Council on Dental Therapeutics, Guidelines for
  the Acceptance of Peroxide-Containing Oral Hygiene Products. JADA 125(8): 1140-1142, 1994)}.

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