TY - JOUR T1 - Visible blue light inactivates SARS-CoV-2 variants and inhibits Delta replication in differentiated human airway epithelia JF - bioRxiv DO - 10.1101/2022.01.25.477616 SP - 2022.01.25.477616 AU - Jacob Kocher AU - Leslee Arwood AU - Rachel C. Roberts AU - Ibrahim Henson AU - Abigail Annas AU - David Emerson AU - Nathan Stasko AU - M. Leslie Fulcher AU - Marisa Brotton AU - Scott H. Randell AU - Adam S. Cockrell Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/01/31/2022.01.25.477616.abstract N2 - The emergence of SARS-CoV-2 variants that evade host immune responses has prolonged the COVID-19 pandemic. Thus, the development of an efficacious, variant-agnostic therapeutic for the treatment of early SARS-CoV-2 infection would help reduce global health and economic burdens. Visible light therapy has the potential to fill these gaps. In this study, visible blue light centered around 425 nm efficiently inactivated SARS-CoV-2 variants in cell-free suspensions and in a translationally relevant well-differentiated tissue model of the human large airway. Specifically, 425 nm light inactivated cell-free SARS-CoV-2 variants Alpha, Beta, Delta, Gamma, Lambda, and Omicron by up to 99.99% in a dose-dependent manner, while the monoclonal antibody bamlanivimab did not neutralize the Beta, Delta, and Gamma variants. Further, we observed that 425 nm light reduced virus binding to host ACE-2 receptor and limited viral entry to host cells in vitro. Further, the twice daily administration of 32 J/cm2 of 425 nm light for three days reduced infectious SARS-CoV-2 Beta and Delta variants by >99.99% in human airway models when dosing began during the early stages of infection. In more established infections, logarithmic reductions of infectious Beta and Delta titers were observed using the same dosing regimen. Finally, we demonstrated that the 425 nm dosing regimen was well-tolerated by the large airway tissue model. Our results indicate that blue light therapy has the potential to lead to a well-tolerated and variant-agnostic countermeasure against COVID-19.Competing Interest StatementAuthors J.K., L.A., R.C.R., I.H., A.A., D.E., N.S., A.S.C. conducted this work on behalf of EmitBio Inc. through their employment relationship with KNOWBioLLC (parent company of EmitBio) and may have ownership interests in one or both companies. All patents and applications arising from these findings are assigned to KNOWBioLLC. ER -