Photodynamic inactivation of pathogenic microorganisms can be successfully used to eradicate pathogens in localized lesions, infected liquid media, and on various surfaces. This technique utilizes the photosensitizer (PS), light, and molecular oxygen to produce reactive oxygen species that kill pathogens. Here, we used the PS, water soluble octakis(cholinyl)zinc phthalocyanine (Zn-PcChol8+), to inactivate an initial 4.75–5.00 IgTCID50/mL titer of SARS-CoV-2, thereby preventing viral infection when tested in Vero E6 cell cultures. Zn-PcChol8+ in a minimally studied concentration, 1 µM and LED 3.75 J/cm2, completely destroyed the infectivity of SARS-CoV-2. To detect possible PS binding sites on the envelope of SARS-CoV-2, we analyzed electrostatic potential and simulated binding of Zn-PcChol8+ to the spike protein of this coronavirus by means of Brownian dynamics software, ProKSim (Protein Kinetics Simulator). Most of the Zn-PcChol8+ molecules formed clusters at the upper half of the stalk within a vast area of negative electrostatic potential. Positioning of the PS on the surface of the spike protein at a distance of no more than 10 nm from the viral membrane may be favorable for the oxidative damage. The high sensitivity of SARS-CoV-2 to photodynamic inactivation by Zn-PcChol8+ is discussed with respect to the application of this PS to control the spread of COVID-19.
The COVID-19 pandemic has updated research on inactivation of coronaviruses with physical, chemical, and physical-chemical treatments. The review focuses on the inactivation of coronaviruses including the recent SARS-CoV-2 and viruses of other groups with analogous structure using optical radiation. The antiviral effects of different optical ranges from vacuum ultraviolet to infrared radiation are described in terms of the mechanisms of virus photoinactivation, sensitive molecular targets and efficacy. Direct and photosensitized damaging effects of light on the viral molecular structures are considered. Information on the applied pathogen photoinactivation technologies and the advantages of light sources for future applications is provided.
Bovine coronaviruses (BCoVs), which cause gastrointestinal and respiratory diseases in cattle, and are genetically related to the human coronavirus HCoV-OC43, which is responsible for up to 10% of common colds, attract increased attention. We applied the method of photodynamic inactivation with cationic photosensitizers (PSs) to reduce the titers of BCoV and studied the morphological structure of viral particles under various modes of photodynamic exposure. The samples of virus containing liquid with an initial virus titer of 5 Log10 TCID50/mL were incubated with methylene blue (MB) or octakis(cholinyl)zinc phthalocyanine (Zn-PcChol8+) at concentrations of 1–5 μM for 10 min in the dark at room temperature. After incubation, samples were irradiated with LED (emission with maximum at 663 nm for MB or at 686 nm for Zn-PcChol8+) with light doses of 1.5 or 4 J/cm2. Next, the irradiation titrated virus containing liquid was studied using negative staining transmission electron microscopy. MB and Zn-PcChol8+ at concentrations of 1–5 μM, in combination with red light from LED sources in the low doses of 1.5–4.0 J/cm2, led to a decrease in BCoV titers by at least four orders of magnitude from the initial titer 5 Log10 TCID50/mL. Morphological changes in photodamaged BCoVs with increasing PS concentrations were loss of spikes, change in shape, decreased size of virus particles, destruction of the envelope, and complete disintegration of viruses. BCoV has been found to be sensitive to MB, which is the well-known approved drug, even in the absence of light.
Antibacterial photodynamic therapy is a promising method of treating local infected foci, especially surgical and burn wounds, trophic and diabetic ulcers. This work explores the photophysical and antibacterial properties of novel phthalocyanine- and synthetic-bacteriochlorin-based octacationic photosensitizers (PS). The results of the study confirm their low degree of aggregation at high concentrations, as well as high efficiency of photodynamic treatment of Gram-negative bacterial biofilms.
The photodynamic activity and pharmacokinetics of a new liposomal form (LF) of the sensitizer Photosense based on aluminum sulfophthalocyanine salts have been studied in comparison to those of the standard form (SF) representing a 0.2% aqueous solution of the parent substance. The effective therapeutic doze of the LF of Photosense in mice bearing Ehrlich's tumor was 1 mg/kg, which is four times as small as the effective dose of the SF. The selectivity of accumulation in the tumor tissue 24 h after administration for the LF of Photosense was 1.5 times higher than for the SF. The drug accumulation in skin (determined by the fluorescence intensity) on the 7th days of experiment for the LF of Photosense was 1.6 times lower than for the SF. The pharmacokinetics of the LF of Photosense in mice without tumors significantly differs from the behavior of the SF.In recent years, the photodynamic therapy (PDT) and fluorescent diagnostics (FLD) of neoplasms have been extensively developed both in the experimental oncology and on the clinical level. In Russia, several potential photosensitizers for PDT and FLD are currently under clinical investigation [1 -4]. Among these, most thoroughly studied is Photosense -a domestic photosensitizer of the second generation -representing a mixture of sodium salts of sulfonated aluminum phthalocyanine, which is synthesized using an original patented technology developed at the State Research Institute of Organic Semiproducts and Dyes (Moscow) [5,6].Previous investigations into the mechanisms of the photodynamic damage of inoculated tumors by Photosense showed that the therapeutic activity of this drug is a multifactor process including (i) necrosis and apoptosis of tumor cells under the direct action of cytotoxic agents (singlet oxygen, free radicals) generated in the course of PDT and (ii) ischemic necrosis caused by the violated blood flow in vessels of the tumor [7]. The results of pathomorphological investigations [7] showed that the direct photodynamic effect of Photosense on the cells and tissues of parenchyma was more pronounced when the period of time between the photosensitizer administration and irradiation exceeds 24 h. The active components of Photosense have various degrees of sulfonation and, hence, differently penetrate through vessel walls and influence the parenchyma [8,9]. The amphiphilic character of the photosensitizer also significantly influences the ability of Photosense to penetrate through the membranes of tumor cells. The attachment of two biotin residues to the molecule of Photosense provided for nearly optimum amphiphilic properties and significantly increased the efficacy of the drug action [10].
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