key: cord-0895112-ctaf9j1f
authors: Denys, G.A.; Burningham, K.; Dyba, J.; Allen, R.C.; Stephens, J.T.
title: Myeloperoxidase-mediated solution demonstrates rapid virucidal properties against the delta variant of SARS-CoV-2
date: 2022-02-23
journal: J Hosp Infect
DOI: 10.1016/j.jhin.2022.02.013
sha: 5cca4061e38118925a58ba3f326761346235acdd
doc_id: 895112
cord_uid: ctaf9j1f

nan

Since coronavirus SARS-CoV-2 was first discovered as the causative agent of the COVID-19 pandemic, there have remained unmet infection prevention needs. Despite many mitigation efforts and discovery of new variants, COVID-19 cases continue to increase [1] . As such, we investigated the in-vitro antiviral efficacy of a myeloperoxidase-mediated solution (MPMS) as a potential oral rinse and nasal spray against coronavirus.

MPMS is a first-in-class tissue-safe topical myeloperoxidase-mediated formulation developed to reduce the microbial burden of pathogens on mucosal and epithelial surfaces. The active ingredients in MPMS are two enzymes: porcine myeloperoxidase (pMPO) and glucose oxidase (GO) in an aqueous solution. The enzymes are activated by the addition of a glucose solution. Once activated, the reactive species hydrogen peroxide, hypochlorous acid, and singlet oxygen are generated [2] . A virucidal suspension test (in-vitro time-kill method) based on ASTM E1052-11 was used [3] . In the virucidal suspension test, a 0.5 mL aliquot of test virus was added to 4.5 mL MPMS with and without mucin at a 90% (v/v) concentration. The mixtures were exposed for 1 or 15 min. After each exposure time, the mixture was neutralized to stop viricidal activity and plated in four replicates. The plates were incubated in CO2 for 7-21 days at 33 ± 2°C and monitored for cytopathic/cytotoxic effect. Viral titre, 50% tissue culture infectious dose (TCID50), was J o u r n a l P r e -p r o o f calculated by the Spearman-Karber method [4] . All testing was performed at Bioscience Laboratories, LLC, Bozeman, MT, USA.

The results of the virucidal suspension test (in-vitro time-kill method) for SARS-CoV-2 delta variant and coronavirus OC43 are shown in Table I SARS-CoV-2 utilizes a pathogenic process that involves human mucosa as the infection entry gate followed by virus dissemination into susceptible organs. The mechanism of cellular entry by SARS-CoV-2 is through the binding to angiotensin-converting enzyme 2 (ACE2) receptor. Elevated ACE2 receptor protein in the upper respiratory tract provides evidence for the initial site of SARS-CoV-2 entry and replication [5] . With high concentrations of virus in the throat and oral cavity, the viral replication cycle promotes further infectivity or dissemination of virus, thus advocating the use or oral antiseptics. Several commercially available oral rinses have been described to have inactivating properties in vitro against SARS-CoV-2 [6] . MPMS differs from these commercial rinses in that it is a formulated cell-free oxidant-generating enzyme system which mimics the intrinsic in-situ functions of the phagolysosome [7] . We found that SARS-CoV-2 delta variant can be efficiently inactivated by MPMS within 1 min of exposure. At a low concentration, MPMS continued to demonstrate activity at 15 min against coronavirus OC43. The presence of mucin at concentration for healthy humans and stage III chronic obstructive pulmonary disorder patients did not interfere with the activity of MPMS [8] . The rapid rate of viral inactivation induced by MPMS is consistent with the combustive oxygenation mechanism of action, which is advantageous in the treatment of new coronavirus variants. 

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