Lysozyme Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Inflammation in Human Corneal Epithelial Cells

Abstract

Purpose The purpose of this study was to investigate the effects of lysozyme, an antimicrobial enzyme found in tears that protects the eye against pathogens, on pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through corneal epithelial cells. Methods The expression of the angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease (TMPRSS2) in human corneal epithelial cells (HCECs) was measured by RT-PCR and Western blotting. The altered expression of the pro-inflammatory molecules induced by spike protein and lysozyme was analyzed by RT-PCR. Cell toxicity was tested by CCK8 assay. The cell entry of SAR-CoV-2 in HCECs and primary rabbit corneal epithelial cells (RbCECs) was detected by luciferase assay. Results ACE2 and TMPRSS2 were highly expressed in HCECs. The spike proteins of SARS-CoV-2 stimulated a robust inflammatory response in HCECs, characterized by increased secretion of pro-inflammatory molecules, including IL-6, TNF-α, iNOS, and MCP-1, and pretreatment with lysozyme in HCECs markedly decreased the production of proinflammatory molecules induced by spike proteins. In addition, the inflammatory cytokine TNF-α enhanced the entry of SARS-CoV-2 into HCECs, which can be mitigated by pretreatment with lysozyme. Conclusions In this study, we analyzed the susceptibility of human corneal epithelial cells to SARS-CoV-2 infection and suggested the protective effects of lysozyme on SARS-CoV-2 infection.

Story of an infection: viral dynamics and host responses in theCaenorhabditis elegans-Orsay virus pathosystem

“…Lysozymes form part of the innate immune response and the digestive system (Boehnisch et al, 2011; Gravato-Nobre et al, 2016). Lysozymes are mostly considered antimicrobial enzymes, but some reports have also described antiviral properties (Ferrari et al, 1959; Lee-Huang et al, 1999), including a recent study which found that lysozyme reduced the entry of SARS-CoV-2 in human epithelial cells (Song et al, 2022). In C. elegans , lysozymes have not been reported to be involved in the defense response against viruses (Dierking et al, 2016).…”

Preventing Respiratory Viral Diseases with Antimicrobial Peptide Master Regulators in the Lung Airway Habitat

“…Additionally, Immuno-depletion experiments revealed a strong antibacterial role for lysozyme in lung airways [ 71 ]. In a recent study, lysozyme was reported to have protective effects against SARS-CoV-2 in human corneal epithelial cells [ 72 ]. Interestingly, niclosamide-lysozyme particles were revealed to have potential anti-coronavirus activities and were suggested to develop as a therapeutic agent [ 73 ].…”

Preventative and therapeutic potential of animal milk components against COVID‐19: A comprehensive review

“…Recombinant human LYS is an intriguing possibility for the treatment of pulmonary infections including pneumonia (Griswold et al, 2014 ). According to a study, pretreatment of human corneal epithelial cell lines with LYS (10 mg/mL) resulted in significant reduction in the levels of proinflammatory cytokines, that is, IL‐6, IL‐8, IL‐1β, TNF‐α, and MCP‐1 (monocyte chemo attractant protein‐1), induced by spike proteins of SARS‐CoV‐2 (Song et al, 2022 ). These functions of LYS may make it a suitable candidate for management of hyperinflammatory stage during COVID‐19, but it needs further investigation.…”

“…According to a speculative theory, LYS found in tears, has power to prevent SARS-CoV-2 from entering the cornea and conjunctiva(de Freitas Santoro et al, 2021). Similarly, LYS pretreatment in human corneal epithelial cells reduced the entry of SARS-CoV-2 into normal (in a dose-dependent manner) as well as inflammatory cells(Song et al, 2022). The enzyme LPO catalyzes the formation of hypothiocyanite (OSCNˉ) ions from the oxidation of thiocyanate in the presence of H 2 O 2 .…”