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1.
Viruses ; 14(5)2022 05 15.
Article in English | MEDLINE | ID: covidwho-1855824

ABSTRACT

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.


Subject(s)
Coronavirus OC43, Human , Coronavirus, Bovine , Animals , Cations , Cattle , Methylene Blue , Photosensitizing Agents/pharmacology , Virion
2.
J Photochem Photobiol B ; 227: 112378, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1654818

ABSTRACT

In a recent study, we showed that pulsed blue light (PBL) inactivates as much as 52.3% of human beta coronavirus HCoV-OC43, a surrogate of SARS-CoV-2, and one of the major strains of viruses responsible for the annual epidemic of the common cold. Since curcumin and saliva are similarly antiviral and curcumin acts as blue light photosensitizer, we used Qubit fluorometry and WarmStart RT-LAMP assays to study the effect of combining 405 nm, 410 nm, 425 nm or 450 nm wavelengths of PBL with curcumin, saliva or a combination of curcumin and saliva against human beta coronavirus HCoV-OC43. The results showed that PBL, curcumin and saliva independently and collectively inactivate HCoV-OC43. Without saliva or curcumin supplementation 21.6 J/cm2 PBL reduced HCoV-OC43 RNA concentration a maximum of 32.8% (log10 = 2.13). Saliva supplementation alone inactivated the virus, reducing its RNA concentration by 61% (log10 = 2.23); with irradiation the reduction was as much as 79.1%. Curcumin supplementation alone decreased viral RNA 71.1%, and a maximum of 87.8% with irradiation. The combination of saliva and curcumin reduced viral RNA to 83.1% and decreased the RNA up to 90.2% with irradiation. The reduced levels could not be detected with qPCR. These findings show that PBL in the range of 405 nm to 450 nm wavelength is antiviral against human coronavirus HCoV-OC43, a surrogate of the COVID-19 virus. Further, it shows that with curcumin as a photosensitizer, it is possible to photodynamically inactivate the virus beyond qPCR detectable level using PBL. Since HCoV-OC43 is of the same beta coronavirus family as SARS-CoV-2, has the same genomic size, and is often used as its surrogate, these findings heighten the prospect of similarly inactivating novel coronavirus SARS-CoV-2, the virus responsible for COVID-19 pandemic.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/therapy , Curcumin/pharmacology , Photosensitizing Agents/pharmacology , SARS-CoV-2/drug effects , Saliva/chemistry , Combined Modality Therapy , Coronavirus OC43, Human , Humans , Light , Photochemical Processes , Photochemotherapy , RNA, Viral
3.
ACS Appl Mater Interfaces ; 14(3): 4456-4468, 2022 Jan 26.
Article in English | MEDLINE | ID: covidwho-1619771

ABSTRACT

Coronavirus represents an inspiring model for designing drug delivery systems due to its unique infection machinery mechanism. Herein, we have developed a biomimetic viruslike nanocomplex, termed SDN, for improving cancer theranostics. SDN has a unique core-shell structure consisting of photosensitizer chlorin e6 (Ce6)-loaded nanostructured lipid carrier (CeNLC) (virus core)@poly(allylamine hydrochloride)-functionalized MnO2 nanoparticles (virus spike), generating a virus-mimicking nanocomplex. SDN not only prompted cellular uptake through rough-surface-mediated endocytosis but also achieved mitochondrial accumulation by the interaction of cationic spikes and the anionic mitochondrial surface, leading to mitochondria-specific photodynamic therapy. Meanwhile, SDN could even mediate oxygen generation to relieve tumor hypoxia and, consequently, improve macrophage-associated anticancer immune response. Importantly, SDN served as a robust magnetic resonance imaging (MRI) contrast agent due to the fast release of Mn2+ in the presence of intracellular redox components. We identified that SDN selectively accumulated in tumors and released Mn2+ to generate a 5.71-fold higher T1-MRI signal, allowing for effectively detecting suspected tumors. Particularly, SDN induced synergistic immunophotodynamic effects to eliminate malignant tumors with minimal adverse effects. Therefore, we present a novel biomimetic strategy for improving targeted theranostics, which has a wide range of potential biomedical applications.


Subject(s)
Drug Delivery Systems , Nanoparticles/chemistry , Neoplasms/therapy , SARS-CoV-2/chemistry , Bionics/methods , Cell Line, Tumor , Chlorophyllides/chemistry , Chlorophyllides/pharmacology , Contrast Media/chemistry , Contrast Media/pharmacology , Humans , Immunotherapy/methods , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Neoplasms/immunology , Oxides/chemistry , Oxides/pharmacology , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Polyamines/chemistry , Polyamines/pharmacology
4.
Viruses ; 14(1)2022 01 08.
Article in English | MEDLINE | ID: covidwho-1614009

ABSTRACT

Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species (ROS) that can inactivate microorganisms. The botanical extract PhytoQuinTM is a powerful photosensitizer with antimicrobial properties. We previously demonstrated that photoactivated PhytoQuin also has antiviral properties against herpes simplex viruses and adenoviruses in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. Here, we report that human coronaviruses (HCoVs) are also susceptible to photodynamic inactivation. Photoactivated-PhytoQuin inhibited the replication of the alphacoronavirus HCoV-229E and the betacoronavirus HCoV-OC43 in cultured cells across a range of sub-cytotoxic doses. This antiviral effect was light-dependent, as we observed minimal antiviral effect of PhytoQuin in the absence of photoactivation. Using RNase protection assays, we observed that PDI disrupted HCoV particle integrity allowing for the digestion of viral RNA by exogenous ribonucleases. Using lentiviruses pseudotyped with the SARS-CoV-2 Spike (S) protein, we once again observed a strong, light-dependent antiviral effect of PhytoQuin, which prevented S-mediated entry into human cells. We also observed that PhytoQuin PDI altered S protein electrophoretic mobility. The PhytoQuin constituent emodin displayed equivalent light-dependent antiviral activity to PhytoQuin in matched-dose experiments, indicating that it plays a central role in PhytoQuin PDI against CoVs. Together, these findings demonstrate that HCoV lipid envelopes and proteins are damaged by PhytoQuin PDI and expands the list of susceptible viruses.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus/drug effects , Photosensitizing Agents/pharmacology , Virus Inactivation/drug effects , Animals , Antiviral Agents/radiation effects , Cell Line , Cell Survival/drug effects , Cricetinae , Emodin/pharmacology , Emodin/radiation effects , Humans , Light , Photosensitizing Agents/radiation effects , Plant Extracts/pharmacology , Plant Extracts/radiation effects , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/drug effects , Virion/drug effects
5.
Photodiagnosis Photodyn Ther ; 37: 102642, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1550023

ABSTRACT

The local antiviral photodynamic inactivation (PDI) may prove to be a helpful tool reducing the viral load in the nose and throat area in the early phase of a Covid19 infection. Both the infectivity and the prognosis of SARS-CoV-2 infections in the early phase can depend on the viral load in this area. The aim of our study was to find a simplified PDI therapy option against corona viruses in this region with low dose methylene blue (MB) as photosensitizer and use of LED light instead of laser. As a substitute for SARS-CoV2 viruses we started with BCoV infected U373 cells first. We used an 810nm diode laser with 300mW/cm2 and 100J/cm2 light dose as well as a 590 nm LED and a broadband LED with irradiation intensity of 10,000 lx each (irradiation time 2.5 and 10 min) and concentrations of the sensitizer of 0.001% and 0.0001%. The 0.001% MB sensitizer experiments showed similar results with all exposures. The logarithmic reduction factor varied between ≥ 5.29 and ≥ 5.31, (0.001% MB sensitizer) and ≥ 4.6 and ≥ 5.31 (0.0001% MB) respectively. Extending the LED irradiation time from 2 to 5 and 10 minutes did not change these results. In contrast approaches of BCoV-infected cells in the dark, treated with 0.001% and 0.0001% MB sensitizer alone, a lot of residual viruses could be detected after 10 minutes of incubation (RF 0.9 and RF 1.23 for 0.001% MB and 0.0001% MB respectively) In our SARS-CoV-2 experiments with VERO E6 infected cells the irradiation time was reduced to 1, 2 and 3 minutes for both concentrations with increasing broadband LED radiation intensity from 20 to 50 and 100.000 lx. (RF 4.67 for 0.001% and 0.0001% respectively). This showed a minimum concentration of 0.0001%MB and a minimum radiation intensity of 20,000 lx leads to a 99.99% reduction of intracellular and extracellular viruses after one minute exposure.


Subject(s)
COVID-19 , Photochemotherapy , Humans , Methylene Blue/pharmacology , Methylene Blue/therapeutic use , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , RNA, Viral , SARS-CoV-2
6.
Photochem Photobiol Sci ; 20(11): 1497-1545, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1491552

ABSTRACT

Photodynamic therapy is witnessing a revival of its origins as a response to the rise of multi-drug resistant infections and the shortage of new classes of antibiotics. Photodynamic disinfection (PDDI) of microorganisms is making progresses in preclinical models and in clinical cases, and the perception of its role in the clinical armamentarium for the management of infectious diseases is changing. We review the positioning of PDDI from the perspective of its ability to respond to clinical needs. Emphasis is placed on the pipeline of photosensitizers that proved effective to inactivate biofilms, showed efficacy in animal models of infectious diseases or reached clinical trials. Novel opportunities resulting from the COVID-19 pandemic are briefly discussed. The molecular features of promising photosensitizers are emphasized and contrasted with those of photosensitizers used in the treatment of solid tumors. The development of photosensitizers has been accompanied by the fabrication of a variety of affordable and customizable light sources. We critically discuss the combination between photosensitizer and light source properties that may leverage PDDI and expand its applications to wider markets. The success of PDDI in the management of infectious diseases will ultimately depend on the efficacy of photosensitizers, affordability of the light sources, simplicity of the procedures, and availability of fast and efficient treatments.


Subject(s)
Communicable Disease Control/methods , Drug Resistance, Microbial/drug effects , Drug Resistance, Multiple/drug effects , Photochemotherapy , Photosensitizing Agents/therapeutic use , Animals , Bacteria/drug effects , Biofilms/drug effects , Fungi/drug effects , Humans , Microbial Sensitivity Tests , Neoplasms/drug therapy , Photosensitizing Agents/pharmacology
7.
J Am Chem Soc ; 143(43): 17891-17909, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1483091

ABSTRACT

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.


Subject(s)
Anti-Infective Agents/chemistry , Drug Design , Phototherapy/methods , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Bacteria/drug effects , Biofilms/drug effects , Biofilms/radiation effects , Coloring Agents/chemistry , Coloring Agents/pharmacology , Equipment and Supplies/microbiology , Equipment and Supplies/virology , Escherichia coli/drug effects , Escherichia coli/physiology , Eye Diseases/drug therapy , Eye Diseases/pathology , Fungi/drug effects , Graphite/chemistry , Light , Nanoparticles/chemistry , Nanoparticles/toxicity , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Quantum Theory , Reactive Oxygen Species/metabolism , Viruses/drug effects
8.
Sci Rep ; 11(1): 19029, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1437689

ABSTRACT

The SARS-CoV-2 pandemic has highlighted the weaknesses of relying on single-use mask and respirator personal protective equipment (PPE) and the global supply chain that supports this market. There have been no major innovations in filter technology for PPE in the past two decades. Non-woven textiles used for filtering PPE are single-use products in the healthcare environment; use and protection is focused on preventing infection from airborne or aerosolized pathogens such as Influenza A virus or SARS-CoV-2. Recently, C-H bond activation under mild and controllable conditions was reported for crosslinking commodity aliphatic polymers such as polyethylene and polypropylene. Significantly, these are the same types of polymers used in PPE filtration systems. In this report, we take advantage of this C-H insertion method to covalently attach a photosensitizing zinc-porphyrin to the surface of a melt-blow non-woven textile filter material. With the photosensitizer covalently attached to the surface of the textile, illumination with visible light was expected to produce oxidizing 1O2/ROS at the surface of the material that would result in pathogen inactivation. The filter was tested for its ability to inactivate Influenza A virus, an enveloped RNA virus similar to SARS-CoV-2, over a period of four hours with illumination of high intensity visible light. The photosensitizer-functionalized polypropylene filter inactivated our model virus by 99.99% in comparison to a control.


Subject(s)
COVID-19/virology , Diazomethane/chemistry , Light , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Polypropylenes/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/radiation effects
10.
Small ; 17(30): e2101770, 2021 07.
Article in English | MEDLINE | ID: covidwho-1287404

ABSTRACT

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.


Subject(s)
COVID-19 , Photochemotherapy , Humans , Pandemics , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , SARS-CoV-2
12.
Photodiagnosis Photodyn Ther ; 34: 102324, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1219122

ABSTRACT

BACKGROUND: SARS-CoV-2 attacks hemoglobin through its structural protein ORF3a, dissociating the iron from the heme, as iron is necessary by cell machinery for virus replication. In this process protoporphyrin (PpIX) is released. METHODS: The decrease in the hemoglobin levels observed in patients with Covid-19 is frequently accompanied by an increase in PpIX levels. This evidence was confirmed by the quantification of PpIX by high-performance liquid chromatography (HPLC). PpIX emission is observed in its two characteristic bands at approximately 635 nm and 705 nm. RESULTS: This paper searches to understand the role of heme and PpIX inside the cells. Perspectives on the use of PpIX fluorescence as a sensor to monitor the presence of SARS-CoV-2 in the tissue, blood, urine, or feces to map the evolution and severity of the disease or to monitor the response of the Covid-19 treatment modalities were described. CONCLUSION: Fluorescence spectroscopy could be adopted as an excellent diagnostic technique for Covid-19, of low cost and high sensitivity. This method can potentially be used as a marker to monitor the response to the treatments. Photodynamic and sonodynamic therapies using the endogenous PpIX increased in the acute phase of the disease, could be employed for Covid-19 treatment.


Subject(s)
COVID-19 , Photochemotherapy , Aminolevulinic Acid , COVID-19/drug therapy , Hemoglobins , Humans , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Protoporphyrins , SARS-CoV-2
14.
Viruses ; 13(4)2021 04 09.
Article in English | MEDLINE | ID: covidwho-1178430

ABSTRACT

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.


Subject(s)
Indoles/pharmacology , Organometallic Compounds/pharmacology , Photosensitizing Agents/pharmacology , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/chemistry , Virus Inactivation/drug effects , Animals , COVID-19/prevention & control , Chlorocebus aethiops , Indoles/chemistry , Isoindoles , Light , Molecular Dynamics Simulation , Organometallic Compounds/chemistry , Photosensitizing Agents/chemistry , Vero Cells , Zinc Compounds
15.
Photodiagnosis Photodyn Ther ; 34: 102286, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1171227

ABSTRACT

BACKGROUND: In this study, the ability of antimicrobial photodynamic therapy (aPDT) as a treatment approach and adjuvant therapy using curcumin-poly (lactic-co-glycolic acid) nanoparticles (Cur@PLGA-NPs) to inactivate Coronavirus disease 2019 (COVID-19) in plasma was investigated. Furthermore, to verify whether the quality requirement of aPDT-treated plasma is acceptable, the differences of the levels of clotting factors, total plasma proteins, and anti-A and/or anti-B antibodies titrations in plasma of patient before and after aPDT treatment were investigated. MATERIALS AND METHODS: Cur@PLGA-NPs was synthesized using Electrospinning process and characterized by different analysis including Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), and Fourier Transform Infrared (FTIR) spectroscopy assays. The presence of the SARS-CoV-2 in the plasma samples of patients suspected of having COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Then, the treated plasma samples with Cur@PLGA-NPs plus blue laser were exposed to Vero cells. Eventually, cell cytotoxicity and apoptotic effects of treated Vero cells were evaluated. Levels of clotting factors including prothrombin time (PT) and activated partial thromboplastin time (APTT), total plasma proteins, and anti-A and/or anti-B antibodies measurements were performed using the coagulometer, method of Bradford, and titration procedure, respectively. RESULTS: The presence of SARS-CoV-2 was positive in 84.3 % of samples. Different concentrations of Cur@PLGA-NPs (3, 5, 7, and 10 % wt.), the irradiation times of blue laser (1, 3, and 5 min), and aPDT with the maximum dosed of blue laser light (522.8 J/cm2) plus 10 % wt. Cur@PLGA-NPs had no cytotoxicity. Although there were significant cell degradation and apoptotic effects in treated Vero cells with treated plasma using 10 % wt. Cur@PLGA-NPs, and a blue laser at an energy density of 522.8 J/cm2, no visible changes in cells and apoptosis were observed following aPDT. Total plasma protein content, PT, APTT, and anti-A and/or anti-B antibodies titers showed no significant changes (P > 0.05 for all comparisons) in treated plasma as compared to untreated plasma. CONCLUSION: aPDT exhibited in vitro anti-COVID-19 activities in the treated plasma containing SARS-COV-2 without Vero cell apoptosis and any adverse effects on plasma quality in aPDT-exposed plasma.


Subject(s)
COVID-19 , Curcumin , Nanoparticles , Photochemotherapy , Animals , Anti-Bacterial Agents , Cell Line , Chlorocebus aethiops , Curcumin/pharmacology , Glycolates , Glycols , Humans , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , SARS-CoV-2 , Vero Cells
16.
Photodiagnosis Photodyn Ther ; 33: 102112, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1137557

ABSTRACT

INTRODUCTION: Recently, the COVID-19 pandemic has spread globally, necessitating the development of new methods for its prevention and treatment. The purpose of this study was to evaluate the antiviral activity of photodynamic therapy (PDT) against SARS-CoV-2 in vitro. METHODS: Vero E6 cells and SARS-CoV-2 isolated in Russia were used for PDT with methylene blue (MB) and Radachlorin. A continuous laser with wavelength λ = 662 nm in doses of 16 J/cm2 and 40 J/cm2 laser irradiation was used for PDT of a viral suspension and SARS-CoV-2-infected cells. The direct cytopathogenic effect of SARS-CoV-2 was evaluated via light microscopy to calculate the TCID50 in the samples and perform statistical analysis. RESULTS: Viral suspensions of SARS-CoV-2 that had a TCID50 greater than 103 were inactivated by PDT in the presence of MB and Radachlorin. Vero E6 cells were protected from 104 TCID50 of SARS-CoV-2 by PDT post infection. The range of protective concentrations was 1.0-10.0 µg/ml and 0.5-5.0 µg/ml for MB and Radachlorin, respectively. Additionally, it was found that MB and Radachlorin also possess significant antiviral activity even without PDT. The 50 % inhibitory concentration (IC50) against 102 TCID50 of SARS-CoV-2 was found to be 0.22 and 0.33 µg/mL with the addition of MB and Radachlorin, respectively, to cells concomitantly with virus, whereas in the case of applying the photosensitizers at 3.5 h post infection, the IC50 was 0.6 and 2.0 µg/mL for MB and Radachlorin, respectively. CONCLUSION: PDT shows high antiviral activity against SARS-CoV-2 when combined with MB and Radachlorin in vitro.


Subject(s)
Methylene Blue/pharmacology , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , SARS-CoV-2/drug effects , Animals , Chlorocebus aethiops , Dose-Response Relationship, Drug , Drug Combinations , Microbiological Techniques , Porphyrins , Vero Cells
17.
Molecules ; 25(19)2020 Sep 23.
Article in English | MEDLINE | ID: covidwho-803884

ABSTRACT

The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10-15 years in order to identify the most promising areas.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Photochemotherapy/methods , Pneumonia, Viral/drug therapy , Porphyrins/pharmacology , Antiviral Agents/chemistry , COVID-19 , Humans , Indoles/chemistry , Indoles/pharmacology , Isoindoles , Pandemics , Photochemical Processes , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Porphyrins/chemistry , SARS-CoV-2 , Virus Attachment/drug effects
18.
ACS Appl Mater Interfaces ; 13(1): 155-163, 2021 Jan 13.
Article in English | MEDLINE | ID: covidwho-997777

ABSTRACT

A substantial increase in the risk of hospital-acquired infections (HAIs) has greatly impacted the global healthcare industry. Harmful pathogens adhere to a variety of surfaces and infect personnel on contact, thereby promoting transmission to new hosts. This is particularly worrisome in the case of antibiotic-resistant pathogens, which constitute a growing threat to human health worldwide and require new preventative routes of disinfection. In this study, we have incorporated different loading levels of a porphyrin photosensitizer capable of generating reactive singlet oxygen in the presence of O2 and visible light in a water-soluble, photo-cross-linkable polymer coating, which was subsequently deposited on polymer microfibers. Two different application methods are considered, and the morphological and chemical characteristics of these coated fibers are analyzed to detect the presence of the coating and photosensitizer. To discern the efficacy of the fibers against pathogenic bacteria, photodynamic inactivation has been performed on two different bacterial strains, Staphylococcus aureus and antibiotic-resistant Escherichia coli, with population reductions of >99.9999 and 99.6%, respectively, after exposure to visible light for 1 h. In response to the current COVID-19 pandemic, we also confirm that these coated fibers can inactivate a human common cold coronavirus serving as a surrogate for the SARS-CoV-2 virus.


Subject(s)
COVID-19/virology , Photosensitizing Agents/pharmacology , Polymers/pharmacology , COVID-19/prevention & control , Escherichia coli/drug effects , Escherichia coli/pathogenicity , Humans , Iatrogenic Disease/prevention & control , Light , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Microfibrils/chemistry , Pandemics , Photosensitizing Agents/chemistry , Polymers/chemistry , Porphyrins/chemistry , Porphyrins/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Singlet Oxygen
20.
Vox Sang ; 115(6): 495-501, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-88638

ABSTRACT

BACKGROUND AND OBJECTIVE: Severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a member of the coronavirus family. Coronavirus infections in humans are typically associated with respiratory illnesses; however, viral RNA has been isolated in serum from infected patients. Coronaviruses have been identified as a potential low-risk threat to blood safety. The Mirasol Pathogen Reduction Technology (PRT) System utilizes riboflavin and ultraviolet (UV) light to render blood-borne pathogens noninfectious, while maintaining blood product quality. Here, we report on the efficacy of riboflavin and UV light against the pandemic virus SARS-CoV-2 when tested in both plasma and platelets units. MATERIALS AND METHODS: Stock SARS-CoV-2 was grown in Vero cells and inoculated into either plasma or platelet units. Those units were then treated with riboflavin and UV light. The infectious titres of SARS-CoV-2 were determined by plaque assay using Vero cells. A total of five (n = 5) plasma and three (n = 3) platelet products were evaluated in this study. RESULTS: In both experiments, the measured titre of SARS-CoV-2 was below the limit of detection following treatment with riboflavin and UV light. The mean log reductions in the viral titres were ≥3·40 and ≥4·53 for the plasma units and platelet units, respectively. CONCLUSION: Riboflavin and UV light effectively reduced the titre of SARS-CoV-2 in both plasma and platelet products to below the limit of detection in tissue culture. The data suggest that the process would be effective in reducing the theoretical risk of transfusion transmitted SARS-CoV-2.


Subject(s)
Betacoronavirus/drug effects , Blood Safety/methods , Blood-Borne Pathogens/drug effects , Photosensitizing Agents/pharmacology , Riboflavin/pharmacology , Ultraviolet Rays , Animals , Betacoronavirus/radiation effects , Blood Platelets/virology , Blood-Borne Pathogens/radiation effects , Chlorocebus aethiops , Humans , Plasma/virology , SARS-CoV-2 , Vero Cells
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