Visible blue light inactivates SARS-CoV-2 variants and inhibits Delta replication in differentiated human airway epithelia

Abstract

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.

Disinfection and decontamination in the context of SARS‐CoV‐2‐specific data

“…Sunlight exposure may serve to decontaminate SARS‐CoV‐2 experimentally, but will depend on the specific virus milieu 85 . Selective use of visible light with wavelengths of 405–425 also inactivates virus in a time‐dependent manner 86–88 . Chemical photosensitization enhances the effects of visible light spectra 89–91 .…”

“… 85 Selective use of visible light with wavelengths of 405–425 also inactivates virus in a time‐dependent manner. 86 , 87 , 88 Chemical photosensitization enhances the effects of visible light spectra. 89 , 90 , 91 It is conceivable that several variations of such exposure could contribute to further practical applications.…”

Influence of colour background on anti‐viral activity against viral haemorrhagic septicaemia virus in zebrafish regulated by circadian rhythm signalling pathway

“…For instance, a study suggested the application of a particular visible light spectrum for inactivating VHSV in fish (Ho et al., 2020). Blue light has also been found to be effective at reducing the infectivity of murine leukaemia virus and coronaviruses (Kocher et al., 2022; Richardson & Porter, 2005). Additionally, a particular light spectrum (405 nm) was successfully applied for controlling SARS‐CoV‐2, influenza A virus and feline calicivirus (Rathnasinghe et al., 2021; Tomb et al., 2017).…”

“…For instance, a study suggested the application of a particular visible light spectrum for inactivating VHSV in fish (Ho et al, 2020). Blue light has also been found to be effective at reducing the infectivity of murine leukaemia virus and coronaviruses (Kocher et al, 2022;Richardson & Porter, 2005).…”

Efficacy and hazards of 425 nm oral cavity light dosing to inactivate SARS-CoV-2

“…Further, in the 16 J/cm 2 early feasibility trial, there were no application site reactions and no device-related serious adverse events reported [ 9 , 11 , 12 ]. Although these prior hazard assessments [ 10 , 13 ] and initial clinical safety analyses are necessary steps toward the development of acute oral cavity light-dosing devices, continuing to evaluate potential hazards (through preclinical studies) and clinical safety (through clinical trials) is necessary, particularly for the novel application of photomedicine in the oral cavity for which there is limited clinical precedent. For this reason, in this work we sought to perform a more systematic preclinical in vitro assessment of the various potential hazards that could result from delivering acute 425 nm light doses to the oral cavity.…”