Photodynamic therapy: a new treatment against COVID-19

In 2019, a new coronavirus (COVID-19) was discovered in Wuhan, China, which soon spread all over the world. The main hallmark of the disease includes fever, diarrhea, vomiting, and dry cough with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS). Currently, no definitive treatment or prevention therapy exists for COVID-19 but scientists and researchers all over the world are relentlessly working to understand COVID-19 to discover novel therapeutic tools and vaccines. Today, photodynamic therapy (PDT) has been investigated as a noninvasive therapy for the treatment of this pandemic and was able to increase the healing process with the help of appropriate photosensitizers by targeting the pathogen inside the patient's body.

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.

Calculation of Electrostatic Potential Field of Coronavirus S Proteins for Brownian Dynamics Simulations

The Brownian dynamics method can give insight into the initial stages of the interaction of antiviral drug molecules with the structural components of bacteria or viruses. RAM of conventional personal computer allows calculation of Brownian dynamics of interaction of antiviral drugs with individual coronavirus S protein. However, scaling up this approach for modeling the interaction of antiviral drugs with the whole virion consisting of thousands of proteins and lipids is difficult due to high requirements for computing resources. In the case of the Brownian dynamics method, the main amount of RAM in the calculations is occupied by an array of values of the virion electrostatic potential field. When the system is increased from one S protein to the whole virion, the volume of data increases significantly. The standard protocol for calculating Brownian dynamics uses a three-dimensional grid with a spatial step of 1°A to calculate the electrostatic potential field. In this work, we consider the possibility of increasing the grid spacing parameter for calculating the electrostatic potential field of individual coronavirus S proteins. In this case, the amount of RAM occupied by the electrostatic potential field is reduced, which makes it possible to use personal computers for calculations. We performed Brownian dynamics simulations of interaction of an antiviral photosensitizer molecule with S proteins of three coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2, and demonstrated that reduction of detalization of electrostatic potential field does not influence the results of Brownian dynamics much © The Authors 2022. This paper is published with open access at SuperFri.org

Hidden threat lurking in extensive hand hygiene during the Covid-19 pandemic: investigation of sensitizing molecules in gel products by hyphenated chromatography techniques.

During the Covid-19 pandemic, health agencies worldwide have recommended frequent handwashing and sanitizing. A variety of hand gel products were made available on the market, often with fragrances added to curtail the strong smell of alcohol. Commonly used Citrus fragrances contain volatile aroma constituents and non-volatile oxygen heterocyclic compounds (OHCs), consisting mostly of polymethoxyflavones, coumarins, and furocoumarins. The latter have long been investigated for their phototoxic properties, and their safety as cosmetic product ingredients has been debated recurrently. To this concern, twelve commercial Citrus-scented products were investigated in this study. An extraction method was optimized for thirty-seven OHC compounds, obtaining absolute mean recovery values in the 73.5-116% range with only few milliliters of solvent consumption. Analysis by ultra-high-pressure liquid chromatography with tandem mass spectrometry detection evidenced that three samples did not conform to the labeling requirements for fragrance allergens (coumarin) laid down by the European Union Regulation on Cosmetic Products. The total furocoumarin (FC) content of the samples investigated was in the 0.003-3.7ppm range, with some noteworthy exceptions. Specifically, in two samples, the total FCs were quantified as 89 and 219 ppm, thus exceeding the safe limits recommended up to a factor of 15. Finally, the consistency of the volatile fingerprint attained by gas chromatography allowed drawing conclusions on the authenticity of the Citrus fragrances labeled, and several products did not conform to the information reported on the label concerning the presence of essential oils. Besides the issue of product authenticity, analytical tools and regulatory actions for widespread testing of hand hygiene products are urgent, to protect consumers' health and safety.

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.

Photodynamic viral inactivation assisted by photosensitizers

The deadly viruses, which are spreading worldwide at an alarming rate, are a major challenge for the life sci-ences. More efficient and cost-effective methods with fewer side effects can provide a good alternative to traditional drug-based methods. Currently, physical phenomena such as light in the form of photodynamic action are increasingly being used to inactivate viruses. Photodynamic inactivation (PDI) uses a photosensitizer (PS), light, and oxygen to generate reactive oxygen species (ROS) to inactivate microorganisms. This article reviews the use of existing PSs, as one of the essential anti-viral agents, and introduces new materials and strategies combined with PDI. Physiochemical properties of PSs and their role in interaction with virus components are discussed. Furthermore, the effectiveness of optical sensitizers with radiation methods to inactivate viruses is highlighted.

The concept of multimodal prevention and treatment of new coronavirus infection COVID-19 by drug photosensitizers and photodynamic therapy on their basis

A study of antiviral low-dose photodynamic therapy with pharmacopoeia photosensitizers in the form of methylene blue and chloride E6 (Radachlorin) solutions in vitro demonstrated complete inactivation of SARS-CoV-2 in suspension and protection of Vero E6 cells even 3.5 hours after their infection with coronavirus at concentrations of photosensitizers 100-1000 times lower than the recommended pharmacopoeia forms of these drugs. © 2022 IEEE.

Photodynamic Therapy as a New Technology for Inactivation of Coronavirus Disease (COVID-19)

Purpose: Coronavirus Disease (COVID-19) could be an emerging disease with a severe acute respiratory infection, and its epidemiology and unique medicinal properties are perpetually increasing. Regarding the lack of COVID-19 controls, this needs current technical events to worsen and treat. Antiviral Photodynamic Therapy (aPDT) could also be effective in reducing and inhibiting the coronavirus. aPDT with various photosensitizers is a very favorable procedure to manage viral infections. Materials and Methods: A total of 37 articles related to the publication of this review manuscript were mentioned. Several scientific databases such as Scopus, PubMed, Web of Science (ISI), and Google Scholar have checked the key phrases of COVID-19, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), photodynamic therapy, and antiviral photodynamic therapy. All 50 main studies were found, and 37 related studies were deemed suitable for this study after review. Results: Studies have shown that aPDT with different photosensitizers can be used to treat viral lung complications caused by infectious pathogens such as Middle East Respiratory Syndrome (MERS), SARS-CoV-2, and influenza. Recent studies have shown that aPDT-mediated Methylene Blue (MB) can help control and eradicate coronavirus. In general, more research is needed to use antiviral photodynamic therapy to control COVID-19. Conclusion: Regarding the lack of treatment for COVID-19, MB-mediated aPDT can help reduce the impact of COVID-19. More evidence is needed to support aPDT as a treatment (SARS-CoV-2). Copyright © 2022 Tehran University of Medical Sciences.

Photodynamic inactivation (PDI) as a promising alternative to current pharmaceuticals for the treatment of resistant microorganisms.

Although the whole world is currently observing the global battle against COVID-19, it should not be underestimated that in the next 30 years, approximately 10 million people per year could be exposed to infections caused by multi-drug resistant bacteria. As new antibiotics come under pressure from unpredictable resistance patterns and relegation to last-line therapy, immediate action is needed to establish a radically different approach to countering resistant microorganisms. Among the most widely explored alternative methods for combating bacterial infections are metal complexes and nanoparticles, often in combination with light, but strategies using monoclonal antibodies and bacteriophages are increasingly gaining acceptance. Photodynamic inactivation (PDI) uses light and a dye termed a photosensitizer (PS) in the presence of oxygen to generate reactive oxygen species (ROS) in the field of illumination that eventually kill microorganisms. Over the past few years, hundreds of photomaterials have been investigated, seeking ideal strategies based either on single molecules (e.g., tetrapyrroles, metal complexes) or in combination with various delivery systems. The present work describes some of the most recent advances of PDI, focusing on the design of suitable photosensitizers, their formulations, and their potential to inactivate bacteria, viruses, and fungi. Particular attention is focused on the compounds and materials developed in our laboratories that are capable of killing in the exponential growth phase (up to seven logarithmic units) of bacteria without loss of efficacy or resistance, while being completely safe for human cells. Prospectively, PDI using these photomaterials could potentially cure infected wounds and oral infections caused by various multidrug-resistant bacteria. It is also possible to treat the surfaces of medical equipment with the materials described, in order to disinfect them with light, and reduce the risk of nosocomial infections.

Recent Advances in Photosensitizers as Multifunctional Theranostic Agents for Imaging-Guided Photodynamic Therapy of Cancer.

In recent years tremendous effort has been invested in the field of cancer diagnosis and treatment with an overall goal of improving cancer management, therapeutic outcome, patient survival, and quality of life. Photodynamic Therapy (PDT), which works on the principle of light-induced activation of photosensitizers (PS) leading to Reactive Oxygen Species (ROS) mediated cancer cell killing has received increased attention as a promising alternative to overcome several limitations of conventional cancer therapies. Compared to conventional therapies, PDT offers the advantages of selectivity, minimal invasiveness, localized treatment, and spatio-temporal control which minimizes the overall therapeutic side effects and can be repeated as needed without interfering with other treatments and inducing treatment resistance. Overall PDT efficacy requires proper planning of various parameters like localization and concentration of PS at the tumor site, light dose, oxygen concentration and heterogeneity of the tumor microenvironment, which can be achieved with advanced imaging techniques. Consequently, there has been tremendous interest in the rationale design of PS formulations to exploit their theranostic potential to unleash the imperative contribution of medical imaging in the context of successful PDT outcomes. Further, recent advances in PS formulations as activatable phototheranostic agents have shown promising potential for finely controlled imaging-guided PDT due to their propensity to specifically turning on diagnostic signals simultaneously with photodynamic effects in response to the tumor-specific stimuli. In this review, we have summarized the recent progress in the development of PS-based multifunctional theranostic agents for biomedical applications in multimodal imaging combined with PDT. We also present the role of different imaging modalities; magnetic resonance, optical, nuclear, acoustic, and photoacoustic in improving the pre-and post-PDT effects. We anticipate that the information presented in this review will encourage future development and design of PSs for improved image-guided PDT for cancer treatment.

A Membrane-Targeting Photosensitizer with Aggregation-Induced Emission Characteristics for Highly Efficient Photodynamic Combat of Human Coronaviruses.

COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in global social and economic disruption, putting the world economy to the largest global recession since the Great Depression. To control the spread of COVID-19, cutting off the transmission route is a critical step. In this work, the efficient inactivation of human coronavirus with photodynamic therapy (PDT) by employing photosensitizers with aggregation-induced emission characteristics (DTTPB) is reported. DTTPB is designed to bear a hydrophilic head and two hydrophobic tails, mimicking the structure of phospholipids on biological membranes. DTTPB demonstrates a broad absorption band covering the whole visible light range and high molar absorptivity, as well as excellent reactive oxygen species sensitizing ability, making it an excellent candidate for PDT. Besides, DTTPB can target membrane structure, and bind to the envelope of human coronaviruses. Upon light irradiation, DTTPB demonstrates highly effective antiviral behavior: human coronavirus treated with DTTPB and white-light irradiation can be efficiently inactivated with complete loss of infectivity, as revealed by the significant decrease of virus RNA and proteins in host cells. Thus, DTTPB sensitized PDT can efficiently prevent the infection and the spread of human coronavirus, which provides a new avenue for photodynamic combating of COVID-19.

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.