The inhibitory and inactivating effects of visible light on SARS-CoV-2: A narrative update.

Prior to the coronavirus disease-19 (COVID-19) pandemic, the germicidal effects of visible light (λ = 400 - 700 nm) were well known. This review provides an overview of new findings that suggest there are direct inactivating effects of visible light - particularly blue wavelengths (λ = 400 - 500 nm) - on exposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions, and inhibitory effects on viral replication in infected cells. These findings complement emerging evidence that there may be clinical benefits of orally administered blue light for limiting the severity of COVID-19. Possible mechanisms of action of blue light (e.g., regulation of reactive oxygen species) and important mediators (e.g., melatonin) are discussed.

Synthesis Strategy of Tetrapyrrolic Photosensitizers for Their Practical Application in Photodynamic Therapy

This review presents a wide range of tetrapyrrole photosensitizers used for photodynamic therapy (PDT), antimicrobial photodynamic therapy, photoinactivation of pathogens. Methods of synthesis and design of new photosensitizers with greater selectivity of accumulation in tumor tissue and increased photoinduced antitumor activity are considered. The issues of studying the properties of new photosensitizers, their photoactivity, the ability to generate singlet oxygen, and the possibility of using targeted photodynamic therapy in clinical practice are discussed. The review examines the work on PDT by national and foreign researchers.

Synthesis of water-soluble porphyrin with tyrosine fragments and study of its interaction with S-protein of SARS-CoV-2.

The multistage purposeful synthesis of 5,15-bis(4'-l-N-tyrosinylamidophenyl)-10,20-bis(N-methylpyridin-3'-yl)porphine diiodide was carried out, and the optimum synthesis conditions were determined. 5,15-Bis(4'-nitrophenyl)-10,20-bis(pyridin-3'-yl)porphine served as the starting porphyrin. The structure, individual character, and purity of the target compound were proved by electron spectroscopy, 1H NMR spectroscopy, mass spectrometry (MALDI TOF), and TLC. Specific features of the interaction of the synthesized porphyrin with S-protein of SARS-CoV-2 were studied using spectral and thermochemical methods, including conditions of photoirradiation. The photoirradiation of the synthesized porphyrin in a complex with the SARS-CoV-2 S-protein can result in the partial oxidation of amino acid residues of the protein and distort its primary and secondary structures. The photoirradiation of the S-protein complex with the porphyrin decreases its thermal resistance to melting by 15 °C compared to the free S-protein and causes porphyrin release.

Comparative Assessment of Pulsed and Continuous LED UV-A Lighting for Disinfection of Contaminated Surfaces.

The germicidal efficacy of LED UV-A lighting has scarcely been compared in continuous and pulsed modes for contaminated surfaces. Herein, we compare the disinfection properties of pulsed versus continuous lighting at equal irradiances using a 365 nm LED device that replicates the doses of occupied-space continuous disinfection UV-A products. Representative organisms evaluated in this study included human-infectious enveloped and non-enveloped viruses (lentivirus and adeno-associated virus, respectively), a bacterial endospore (Bacillus atrophaeus), and a resilient gram-positive bacterium (Enterococcus faecalis). Nominal UV-A irradiances were tested at or below the UL standard limit for continuous human exposure (maximum irradiance of 10 W/m2). We observed photoinactivation properties that varied by organism type, with bacteria and enveloped virus being more susceptible to UV-A than non-enveloped virus and spores. Overall, we conclude that continuous-mode UV-A lighting is better suited for occupied-space disinfection than pulsing UV-A at equivalent low irradiances, and we draw comparisons to other studies in the literature.

Surface disinfection with white-violet illumination device

The spread of infections, as in the coronavirus pandemic, leads to the desire to perform disinfection measures even in the presence of humans. UVC radiation is known for its strong antimicrobial effect, but it is also harmful to humans. Visible light, on the other hand, does not affect humans and laboratory experiments have already demonstrated that intense visible violet and blue light has a reducing effect on bacteria and viruses. This raises the question of whether the development of pathogen-reducing illumination is feasible for everyday applications. For this purpose, a lighting device with white and violet LEDs is set up to illuminate a work surface with 2,400 lux of white light and additionally with up to 2.5 mW/cm2 of violet light (405 nm). Staphylococci are evenly distributed on the work surface and the decrease in staphylococci concentration is observed over a period of 46 hours. In fact, the staphylococci concentration decreases, but with the white illumination, a 90% reduction occurs only after 34 hours;with the additional violet illumination the necessary irradiation time is shortened to approx. 3.5 hours. Increasing the violet component probably increases the disinfection effect, but the color impression moves further away from white and the low disinfection durations of UVC radiation can nevertheless not be achieved, even with very high violet emissions.

Photoinactivation of Catalase Sensitizes Candida albicans and Candida auris to ROS-Producing Agents and Immune Cells.

Microbes have developed their own specific strategies to cope with reactive oxygen species (ROS). Catalase, a heme-containing tetramer expressed in a broad range of aerobic fungi, shows remarkable efficiency in degrading hydrogen peroxide (H2 O2 ) for fungal survival and host invasion. Here, it is demonstrated that catalase inactivation by blue light renders fungal cells highly susceptible to ROS attack. To confirm catalase as a major molecular target of blue light, wild type Candida albicans are systematically compared with a catalase-deficient mutant strain regarding their susceptibility to ROS through 410 nm treatment. Upon testing a wide range of fungal species, it is found that intracellular catalase can be effectively and universally inactivated by 410 nm blue light. It is also found that photoinactivation of catalase in combination with ROS-generating agents is highly effective in total eradication of various fungal species, including multiple Candida auris strains, the causative agent of the global fungal epidemic. In addition, photoinactivation of catalase is shown to facilitate macrophage killing of intracellular Candida albicans. The antifungal efficacy of catalase photoinactivation is further validated using a C. albicans-induced mouse model of skin abrasion. Taken together, the findings offer a novel catalase-photoinactivation approach to address multidrug-resistant Candida infections.

Enhanced viral inactivation by combined ultraviolet light and heat

Viral sensitivity to high temperature and ultraviolet (UV) irradiation has been extensively studied. However, there is still little attention paid to study the joint effect of these two physical factors. Since the outbreak of the COVID-19 pandemic has necessitated the advances of disinfection techniques, rapid and effective viral inactivation by combining heat and UV light is worth investigating. This work focuses on developing such a device combining UV light-emitting diode light sources and a heater. Moreover, two UV bands have been studied in this work, namely 280 nm ultraviolet-C (UVC) and 365 nm ultraviolet-A (UVA. A) control system is developed to accurately control both the heating temperature of the device and the irradiance of the dual-spectral UV light sources. The performance of the device is verified by a series of experimental measurements. More importantly, the disinfection effect of the device has been verified by the experiments based on non-pathogenic carrier virus commonly used in the laboratory. The disinfection doses of the 280 nm UVC and 365 nm UVA light sources under the high temperature synergy have been examined. The experimental results show that when combined with a heating temperature of 60 C-circle, the cumulative UV radiation doses required for sufficient viral inactivation can be greatly reduced.

Minimum irradiance required to inhibit microbial growth to prevent ventilatorassociated pneumonia by an endotracheal tube equipped with blue LEDs

Artificial respiration is saving lives especially in the COVID-19 pandemic, but it also carries the risk to cause ventilator-Associated pneumonia (VAP). VAP is one of the most common and severe nosocomial infections, often leading to death and adding a major economic burden to the healthcare system. To prevent a proliferation of microbial pathogens that cause VAP, an endotracheal tube (ETT) equipped with blue LEDs (LED-ETT) was developed. This blue wavelength exhibits antimicrobial properties but may also harm human tracheal cells at higher irradiances. Therefore, the aim of this study was to find the minimal required irradiance for microbial reduction of 1 log level in 24 h by applying LED-ETTs. A LED-ETT with 48 blue LEDs (450 nm) was fixed in a glass tube, which served as a trachea model. The investigation was carried out with irradiations of 4.2, 6.6 and 13.4 mW/cm² at 37 °C for 24 h. The experiments were performed with Acinetobacter kookii as a surrogate of Acinetobacter baumannii, which is classified as critical by the WHO. Samples of A. kookii suspensions were taken every 4 h during irradiation from the trachea model. Bacteria concentrations were quantified by determining colony forming units (CFU)/ml. A homogeneous irradiance of only 4.2 mW/cm² generated by the blue LEDs, at a LED forward current of 3.125 mA, is sufficient to achieve a 1 log reduction of A. kookii within 24 h. The total irradiation dose within this period was 360 J/cm2. Human cells survive this dose without cellular damage. Previous studies revealed that the pathogen A. baumannii is even more sensitive to blue light than A. kookii. Therefore, blue LED-ETTs are expected to reduce A. baumannii without harming human tracheal cells. © 2021 by Walter de Gruyter Berlin/Boston.

A systematic scoping review of ultraviolet C (UVC) light systems for SARS-CoV-2 inactivation.

A significant amount of epidemiological evidence has underlined that human-to-human transmission due to close contacts is considered the main pathway of transmission, however since the SARS-CoV-2 can also survive in aerosols, water, and surfaces, the development and implementation of effective decontamination strategies are urgently required. In this regard, ultraviolet germicidal irradiation (UVGI) using ultraviolet C (UVC) has been proposed to disinfect different environments and surfaces contaminated by SARS-CoV-2. Herein, we performed a systematic scoping review strictly focused on peer-reviewed studies published in English that reported experimental results of UVC-based technologies against the SARS-CoV-2 virus. Studies were retrieved from PubMed and the Web of Science database. After our criterious screening, we identified 13 eligible articles that used UVC-based systems to inactivate SARS-CoV-2. We noticed the use of different UVC wavelengths, technologies, and light doses. The initial viral titer was also heterogeneous among studies. Most studies reported virus inactivation in well plates, even though virus persistence on N95 respirators and different surfaces were also evaluated. SARS-CoV-2 inactivation reached from 90% to 100% depending on experimental conditions. We concluded that there is sufficient evidence to support the use of UVC-based technologies against SARS-CoV-2. However, appropriate implementation is required to guarantee the efficacy and safety of UVC strategies to control the COVID-19 pandemic.

Blue light inactivation of the enveloped RNA virus Phi6.

OBJECTIVE: Ultraviolet radiation is known for its antimicrobial properties but unfortunately, it could also harm humans. Currently, disinfection techniques against SARS-CoV-2 are being sought that can be applied on air and surfaces and which do not pose a relevant thread to humans. In this study, the bacteriophage phi6, which like SARS-CoV-2 is an enveloped RNA virus, is irradiated with visible blue light at a wavelength of 455 nm. RESULTS: For the first time worldwide, the antiviral properties of blue light around 455 nm can be demonstrated. With a dose of 7200 J/cm2, the concentration of this enveloped RNA virus can be successfully reduced by more than three orders of magnitude. The inactivation mechanism is still unknown, but the sensitivity ratio of phi6 towards blue and violet light hints towards an involvement of photosensitizers of the host cells. Own studies on coronaviruses cannot be executed, but the results support speculations about blue-susceptibility of coronaviruses, which might allow to employ blue light for infection prevention or even therapeutic applications.

Possible therapeutic targets and promising drugs based on unsymmetrical hetaryl-substituted porphyrins to combat SARS-CoV-2.

Coronavirus disease 2019 is a serious disease that causes acute respiratory syndrome and negatively affects the central nervous system. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) crosses the blood-brain barrier due to the spike (S) protein on the surface of the viral particles. Thus, it is important to develop compounds that not only have an inhibitory effect but are also capable of completely deactivating the S protein function. This study describes the purposeful modification of porphyrins and proposes compounds, asymmetrically hetaryl-substituted porphyrins with benzothiazole, benzoxazole, and N-methylbenzimidazole residues, to deactivate the S protein functions. Molecular docking of SARS-CoV-2 proteins with hetaryl-substituted porphyrins showed that the viral S protein, nucleocapsid (N) protein, and non-structural protein 13 (nsp13) exhibited the highest binding affinity. Hetaryl-substituted porphyrins form strong complexes (13-14 kcal/mol) with the receptor-binding domain of the S protein, while the distance from the porphyrins to the receptor-binding motif (RBM) does not exceed 20 Å; therefore, RBM can be oxidized by 1O2, which is generated by porphyrin. Hetaryl-substituted porphyrins interact with the N protein in the serine/arginine-rich region, and a number of vulnerable amino acid residues are located in the photooxidation zone. This damage complicates the packaging of viral RNA into new virions. High-energy binding of hetaryl-substituted porphyrins with the N- and C-terminal domains of nsp13 was observed. This binding blocks the action of nsp13 as an enzyme of exoribonuclease and methyltransferase, thereby preventing RNA replication and processing. A procedure for the synthesis of hetaryl-substituted porphyrins was developed, new compounds were obtained, their structures were identified, and their photocatalytic properties were studied.

UVC-based photoinactivation as an efficient tool to control the transmission of coronaviruses.

The ongoing COVID-19 pandemic made us re-realize the importance of environmental disinfection and sanitation in indoor areas, hospitals, and clinical rooms. UVC irradiation of high energy and short wavelengths, especially in the 200-290-nm range possesses the great potential for germicidal disinfection. These properties of UVC allow to damage or destruct the nucleic acids (DNA/RNA) in diverse microbes (e.g., bacteria, fungi, and viruses). UVC light can hence be used as a promising tool for prevention and control of their infection or transmission. The present review offers insights into the historical perspective, mode of action, and recent advancements in the application of UVC-based antiviral therapy against coronaviruses (including SARS CoV-2). Moreover, the application of UVC lights in the sanitization of healthcare units, public places, medical instruments, respirators, and personal protective equipment (PPE) is also discussed. This article, therefore, is expected to deliver a new path for the developments of UVC-based viricidal approach.

A systematic review of photodynamic therapy as an antiviral treatment: Potential guidance for dealing with SARS-CoV-2.

BACKGROUND: SARS-CoV-2, which causes the coronavirus disease (COVID-19), presents high rates of morbidity and mortality around the world. The search to eliminate SARS-CoV-2 is ongoing and urgent. This systematic review seeks to assess whether photodynamic therapy (PDT) could be effective in SARS-CoV-2 inactivation. METHODS: The focus question was: Can photodynamic therapy be used as potential guidance for dealing with SARS-CoV-2?". A literature search, according to PRISMA statements, was conducted in the electronic databases PubMed, EMBASE, SCOPUS, Web of Science, LILACS, and Google Scholar. Studies published from January 2004 to June 2020 were analyzed. In vitro and in vivo studies were included that evaluated the effect of PDT mediated by several photosensitizers on RNA and DNA enveloped and non-enveloped viruses. RESULTS: From 27 selected manuscripts, 26 publications used in vitro studies, 24 were exclusively in vitro, and two had in vitro/in vivo parts. Only one analyzed publication was exclusively in vivo. Meta-analysis studies were unfeasible due to heterogeneity of the data. The risk of bias was analyzed in all studies. CONCLUSION: The in vitro and in vivo studies selected in this systematic review indicated that PDT is capable of photoinactivating enveloped and non-enveloped DNA and RNA viruses, suggesting that PDT can potentially photoinactivate SARS-CoV-2.

Light-based technologies for management of COVID-19 pandemic crisis.

The global dissemination of the novel coronavirus disease (COVID-19) has accelerated the need for the implementation of effective antimicrobial strategies to target the causative agent SARS-CoV-2. Light-based technologies have a demonstrable broad range of activity over standard chemotherapeutic antimicrobials and conventional disinfectants, negligible emergence of resistance, and the capability to modulate the host immune response. This perspective article identifies the benefits, challenges, and pitfalls of repurposing light-based strategies to combat the emergence of COVID-19 pandemic.