Visible blue light inhibits infection and replication of SARS-CoV-2 at doses that are well-tolerated by human respiratory tissue

Abstract

The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that primary 3D human tracheal/bronchial-derived epithelial tissues tolerated high doses of a narrow spectral band of visible light centered at a peak wavelength of 425 nm. We extended these studies to Vero E6 cells to understand how light may influence the viability of a mammalian cell line conventionally used for assaying SARS-CoV-2. The exposure of single-cell monolayers of Vero E6 cells to similar doses of 425 nm blue light resulted in viabilities that were dependent on dose and cell density. Doses of 425 nm blue light that are well-tolerated by Vero E6 cells also inhibited infection and replication of cell-associated SARS-CoV-2 by > 99% 24 h post-infection after a single five-minute light exposure. Moreover, the 425 nm blue light inactivated cell-free betacoronaviruses including SARS-CoV-1, MERS-CoV, and SARS-CoV-2 up to 99.99% in a dose-dependent manner. Importantly, clinically applicable doses of 425 nm blue light dramatically inhibited SARS-CoV-2 infection and replication in primary human 3D tracheal/bronchial tissue. Safe doses of visible light should be considered part of the strategic portfolio for the development of SARS-CoV-2 therapeutic countermeasures to mitigate coronavirus disease 2019 (COVID-19).

Review of Virus Inactivation by Visible Light

“…Also, in studies on a phage, Tomb et al found approximately a factor of 10 in the log-reduction dose in solutions without riboflavin (1021 J/cm 2 ) and in nutrient medium (113 J/cm 2 ) [40]. This observation of the influence of the medium or the riboflavin concentration on the virus inactivation is quantitatively and qualitatively confirmed by several other authors [37,43,45,48,49,62,63]. In contrast, there is not one report with a higher log-reduction at lower riboflavin concentrations, when different concentrations or media were employed.…”

Blue Laser Light Counteracts HSV-1 in the SH-SY5Y Neuronal Cell Model of Infection

“…Moreover, Oh et al [25], showing the antiviral effect of blue light on SARS-CoV-2 already-infected cells (450 nm, 5.56 mW/cm 2 , 1.6, 5, 10 J/cm 2 ), reported that an antiviral effect was associated with reactive oxygen species (ROS) production, endoplasmic reticulum stress and autophagy progression, inhibiting apoptosis and promoting cell survival. These studies employed minor irradiance with respect to those employed in the current study (0.1 W/cm 2 ), nevertheless the fluence (3 J/cm 2 ) was comparable [25] or higher [12,24]. Our results failed to highlight an antiviral effect in already-infected cells as the three papers cited above showed, however the different virus strains treated, and the different devices employed, could account for the results.…”

“…LED lamps at 450, 454 and 470 nm (CW) were able to cause a decrement in the viral RNA quantity when infected Vero E6 cells were irradiated (450 nm, 0.04 W/cm 2 ; 12.5 J/cm 2 ; 454 nm, 0.04 W/ cm 2 ; 10 J/cm 2 ; 470 nm, 0.04 W/ cm 2 , 20 J/cm 2 ) and relevant decreases were reported, especially at 48 h post-treatment [12]. Stakos et al [24] employed LED light with a peak at 425 nm (dose ranging from 7.5 to 60 J/cm 2 , 50 mW/cm 2 ), on three coronaviruses, i.e., SARS-CoV-2, SARS-CoV-1 and MERS-CoV [24]. When both Vero cells and 3D human tracheal/bronchial-derived epithelial tissue were infected with SARS-CoV-2 and then irradiated, a reduction in viral infection was observed.…”

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

“…Vero E6 and A549 cells were purchased from ATCC. Vero E6 cells were maintained as previously described (Stasko et al, 2021b). A549 cells were maintained according to ATCC instructions.…”

“…A549 cells were maintained according to ATCC instructions. Human adenovirus type 5 (VR-5) was acquired from the ATCC and passaged as previously described (Stasko et al, 2021b).…”