The Therapeutic Potential of Low-Level Laser Therapy in SARS-CoV-2 Infections

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the 2019 coronavirus disease (COVID-19), has presented a significant global health challenge. Originating in bats, with potential transmission through snakes and pangolins, this single-stranded RNA-enveloped virus belongs to the coronavirus family and falls under group four of the Baltimore classification [1-4].

With a death rate of 10%, SARS-CoV-2 has proven more severe than other human coronaviruses, such as HCoV-HKU1, HCoV-NL63, 229E, and HCoV-OC43 [6].

Understanding the genomic makeup of SARS-CoV-2 is crucial, with its complete genome comprising 29,881 base pairs and encoding 9860 amino acids, characterized through next-generation sequencing technology [7].

Viral Structure and Entry Mechanism

The SARS-CoV-2 virus utilizes its surface glycosylated spike (S) proteins to bind to the ACE2 receptor on host cells, facilitating viral entry [9]. The S protein’s two subunits, S1 and S2, play distinct roles in receptor recognition and membrane fusion [10]. The S1 subunit contains a receptor-binding domain that recognizes the host receptor angiotensin-converting enzyme 2 (ACE2), while the S2 subunit facilitates viral cell membrane fusion through a six-helical bundle formation [11].

Low-Level Laser Therapy (LLLT)

Low-level laser therapy (LLLT) emerges as a potential therapeutic approach for various disorders, utilizing red or near-infrared lasers with wavelengths between 632 and 1064 nm and low powers ranging from 1 to 1000 mW [12]. First described by Mester et al. in 1967, LLLT has been used for healing, pain reduction, inflammation control, and functional restoration [13,14]. LLLT functions by activating cellular mitochondria via cytochrome c oxidase, leading to the release of nitric oxide, production of reactive oxygen species (ROS), and accelerated adenosine triphosphate (ATP) synthesis [15].

Cellular Responses to LLLT

The absorption of light by mitochondria triggers cellular responses, including the release of nitric oxide (NO), production of reactive oxygen species (ROS), and acceleration of ATP synthesis [15]. Changes in cellular redox state control the activity of transcription factors, including activator protein-1 (AP-1), redox factor-1 (Ref-1), p53, hypoxia-inducible factor (HIF)-1, nuclear factor kappa B (NF-κB), and activating transcription factor/cAMP-response element-binding protein (ATF/CREB) [16]. These factors contribute to protein synthesis, cell proliferation, movement, growth factor production, increased expression of heat shock proteins, and enhanced antioxidant levels [16].

LLLT in Clinical Applications

LLLT has been successfully applied in various medical conditions, including sports injuries, dermatitis, chronic pain, and hair loss [17]. It has also shown promise in managing tissue swelling, pain, and even cancer [17]. While there is limited research on LLLT’s application in treating viral infections, its potential role in mitigating the effects of SARS-CoV-2 warrants exploration.

Exploring LLLT in SARS-CoV-2 Infections

In the context of the ongoing SARS-CoV-2 pandemic, despite the success of approved vaccines in reducing the spread and mortality rates, the virus continues to evolve with crucial mutations that enhance its infectivity [19]. To address this challenge, it becomes imperative to explore new therapeutic approaches. This study aims to investigate, for the first time, the effects of LLLT on SARS-CoV-2-infected HEK293/ACE2 cells and compare them to uninfected ones.

Discussion

The results presented in this study shed light on the impact of laser irradiation on SARS-CoV-2 infection in HEK293/ACE2 cells. The experimental design involved stimulating uninfected HEK293/ACE2 cells with laser irradiation, while also examining the effects on infected cells. The data obtained from various assays and microscopy observations provide valuable insights into the potential therapeutic role of laser light in treating SARS-CoV-2 infections.

Differential Response to Laser Irradiation

Infected Cells at 10 J/cm²:

The most striking observation was made when infected cells were irradiated at 10 J/cm², resulting in a substantial increase in dead cells, as evidenced by Figure 1. This phenomenon was corroborated by the lowest percentage viability (59%) in Figure 2, accompanied by elevated LDH levels (Figure 3) and increased luciferase activity (Figure 4). The surge in LDH levels suggests a significant number of non-viable cells, indicating a detrimental effect of high fluences on infected cells. The correlation observed between percentage viability, luciferase activity, and LDH levels underscores the severe stress induced by high fluences, leading to reduced cell viability and increased cellular damage.

Lower Fluences (2 J/cm², 4 J/cm², 6 J/cm², and 8 J/cm²):

Contrastingly, no significant difference in cell viability was observed in infected cells irradiated at lower fluences (2 J/cm², 4 J/cm², 6 J/cm², and 8 J/cm²). These results were consistent across multiple assays, including LDH levels (Figure 4) and cell viability (Figure 5). Cells irradiated at 6 J/cm² and 8 J/cm² displayed low LDH release, while those irradiated at 4 J/cm² exhibited no significant difference compared to infected non-irradiated cells. The viability of cells irradiated at 4 J/cm², 6 J/cm², and 8 J/cm² mirrored that of infected non-irradiated cells, indicating the resilience of these cells to the specified fluences. Notably, cells irradiated at 8 J/cm² demonstrated a drastic reduction in luciferase activity despite high percentage viability, suggesting a nuanced response to laser irradiation.

Implications for SARS-CoV-2 Treatment

Laser Irradiation and SARS-CoV-2 Infection:

The overall trend observed in this study points towards the potential of laser irradiation in mitigating SARS-CoV-2 infection. The significant reduction in infected cell viability, particularly at higher fluences, suggests a potential therapeutic avenue for managing SARS-CoV-2 infections. Importantly, the lack of a definitive cure for SARS-CoV-2 necessitates the exploration of novel and effective treatment methods.

Exploring Low-Level Laser Therapy (LLLT):

The study aligns with the existing literature on low-level laser therapy (LLLT), positioning it as a non-aggressive therapeutic approach. The exploration of laser light as a treatment modality for SARS-CoV-2 aligns with the broader applications of LLLT in various biological contexts. Further research is imperative to delve deeper into the mechanisms through which laser irradiation exerts its antiviral effects on SARS-CoV-2-infected cells.

Future Directions and Recommendations

The current study provides a foundation for further investigations into the therapeutic potential of laser irradiation against SARS-CoV-2. Future studies should incorporate advanced imaging techniques, such as transmission electron microscopy (TEM), to explore the interior of cells and complement the findings obtained from scanning electron microscopy (SEM). A detailed examination of the molecular and cellular changes induced by laser irradiation can offer a more comprehensive understanding of the antiviral mechanisms at play.

In conclusion, the results presented in this study indicate a promising role for laser light in mitigating SARS-CoV-2 infection. This opens avenues for future research, emphasizing the need for a deeper understanding of the underlying mechanisms and the potential integration of laser therapy into the repertoire of treatment options for SARS-CoV-2.


reference link : https://onlinelibrary.wiley.com/doi/10.1002/jbio.202300334

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