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1.
Int J Mol Sci ; 23(13)2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1917518

ABSTRACT

Electrostatics is an important part of virus life. Understanding the detailed distribution of charges over the surface of a virus is important to predict its interactions with host cells, antibodies, drugs, and different materials. Using a coarse-grained model of the entire viral envelope developed by D. Korkin and S.-J. Marrink's scientific groups, we created an electrostatic map of the external surface of SARS-CoV-2 and found a highly heterogeneous distribution of the electrostatic potential field of the viral envelope. Numerous negative patches originate mainly from negatively charged lipid domains in the viral membrane and negatively charged areas on the "stalks" of the spike (S) proteins. Membrane (M) and envelope (E) proteins with the total positive charge tend to colocalize with the negatively charged lipids. In the E protein pentamer exposed to the outer surface, negatively charged glutamate residues and surrounding lipids form a negative electrostatic potential ring around the channel entrance. We simulated the interaction of the antiviral octacationic photosensitizer octakis(cholinyl)zinc phthalocyanine with the surface structures of the entire model virion using the Brownian dynamics computational method implemented in ProKSim software (version r661). All mentioned negatively charged envelope components attracted the photosensitizer molecules and are thus potential targets for reactive oxygen generated in photosensitized reactions.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/chemistry , Binding Sites , Cations , Humans , Lipids , Photosensitizing Agents/chemistry , Static Electricity , Virion
2.
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
3.
Sci Rep ; 12(1): 6580, 2022 04 21.
Article in English | MEDLINE | ID: covidwho-1805652

ABSTRACT

The development of effective pathogen reduction strategies is required due to the rise in antibiotic-resistant bacteria and zoonotic viral pandemics. Photodynamic inactivation (PDI) of bacteria and viruses is a potent reduction strategy that bypasses typical resistance mechanisms. Naturally occurring riboflavin has been widely used in PDI applications due to efficient light-induced reactive oxygen species (ROS) release. By rational design of its core structure to alter (photo)physical properties, we obtained derivatives capable of outperforming riboflavin's visible light-induced PDI against E. coli and a SARS-CoV-2 surrogate, revealing functional group dependency for each pathogen. Bacterial PDI was influenced mainly by guanidino substitution, whereas viral PDI increased through bromination of the flavin. These observations were related to enhanced uptake and ROS-specific nucleic acid cleavage mechanisms. Trends in the derivatives' toxicity towards human fibroblast cells were also investigated to assess viable therapeutic derivatives and help guide further design of PDI agents to combat pathogenic organisms.


Subject(s)
COVID-19 , Photochemotherapy , Bacteria , Escherichia coli , Humans , Light , Photosensitizing Agents/chemistry , Reactive Oxygen Species/pharmacology , Riboflavin/pharmacology , SARS-CoV-2
4.
Photodiagnosis Photodyn Ther ; 38: 102743, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1661892

ABSTRACT

Several oral lesions related to COVID-19 have been described in the scientific literature. The COVID-19 pandemic highlighs importance of supportive protocols, which can reduce the inflammation and aid in tissue repair in severe cases. Photobiomodulation therapy (PBMT) alone or in combination with antimicrobial photodynamic therapy (aPDT) can be used to manage orofacial lesions in confirmed cases of COVID-19. Here, we sought to describe the clinical presentation and specificities of three cases in which aPDT and PBMT were used to manage orofacial lesions in patients with COVID-19. The laser protocols were effective with improvement of the orofacial lesions within a few days.


Subject(s)
Anti-Infective Agents , COVID-19 , Low-Level Light Therapy , Photochemotherapy , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Humans , Low-Level Light Therapy/methods , Multicenter Studies as Topic , Pandemics , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , SARS-CoV-2
5.
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
6.
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
7.
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
8.
Photodiagnosis Photodyn Ther ; 37: 102678, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1562141

ABSTRACT

Opportunistic infections are widely described in patients with novel coronavirus disease 2019 (COVID-19); however, very few studies have addressed those affecting the oral cavity. Given the lack of information on the clinical presentations and the available treatment options, the present study aimed to show a case in which a combination of antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) was used for the management of two concomitant COVID-19-associated opportunistic oral infections (oral pseudomembranous candidiasis and recurrent herpes labialis). Within 7 days and without any systemic drug administration, all the lesions resolved completely, and the patient no longer reported oral pain or discomfort. According to the current case report and taking into consideration the significant gaps in the knowledge and understanding of COVID-19, this combination of phototherapy modalities seems to be a promising tool for managing viral and fungal opportunistic oral infections.


Subject(s)
COVID-19 , Opportunistic Infections , Photochemotherapy , Humans , Opportunistic Infections/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , SARS-CoV-2
9.
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
10.
Theranostics ; 11(18): 9054-9088, 2021.
Article in English | MEDLINE | ID: covidwho-1524532

ABSTRACT

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.


Subject(s)
Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Precision Medicine/methods , Humans , Neoplasms/therapy , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/metabolism , Reactive Oxygen Species , Theranostic Nanomedicine/methods , Tumor Microenvironment/drug effects
11.
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
12.
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
13.
Adv Sci (Weinh) ; 8(23): e2100118, 2021 12.
Article in English | MEDLINE | ID: covidwho-1482096

ABSTRACT

Recently, viral infectious diseases, including COVID-19 and Influenza, are the subjects of major concerns worldwide. One strategy for addressing these concerns focuses on nasal vaccines, which have great potential for achieving successful immunization via safe, easy, and affordable approaches. However, conventional nasal vaccines have major limitations resulting from fast removal when pass through nasal mucosa and mucociliary clearance hindering their effectiveness. Herein a nanoparticulate vaccine (NanoVac) exhibiting photochemical immunomodulation and constituting a new self-assembled immunization system of a photoactivatable polymeric adjuvant with influenza virus hemagglutinin for efficient nasal delivery and antigen-specific immunity against pathogenic influenza viruses is described. NanoVac increases the residence period of antigens and further enhances by spatiotemporal photochemical modulation in the nasal cavity. As a consequence, photochemical immunomodulation of NanoVacs successfully induces humoral and cellular immune responses followed by stimulation of mature dendritic cells, plasma cells, memory B cells, and CD4+ and CD8+ T cells, resulting in secretion of antigen-specific immunoglobulins, cytokines, and CD8+ T cells. Notably, challenge with influenza virus after nasal immunization with NanoVacs demonstrates robust prevention of viral infection. Thus, this newly designed vaccine system can serve as a promising strategy for developing vaccines that are active against current hazardous pathogen outbreaks and pandemics.


Subject(s)
Hemagglutinins/chemistry , Influenza Vaccines/administration & dosage , Light , Nanoparticles/chemistry , Orthomyxoviridae Infections/prevention & control , Adjuvants, Immunologic/administration & dosage , Administration, Inhalation , Animals , Antigens/administration & dosage , Antigens/chemistry , Antigens/immunology , Dendritic Cells/cytology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Hemagglutinins/administration & dosage , Hemagglutinins/immunology , Humans , Immunity, Cellular , Immunity, Humoral , Influenza Vaccines/chemistry , Influenza Vaccines/immunology , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Interferon-gamma/metabolism , Male , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Photosensitizing Agents/chemistry , Polymers/chemistry
14.
Photodiagnosis Photodyn Ther ; 36: 102577, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1458876

ABSTRACT

PURPOSE: To investigate the short-term effect of coronavirus 2019 (COVID-19) on the retinal capillary network and choroid in children. MATERIALS AND METHODS: This prospective, cross-sectional, case-control study included 19 recovered COVID-19 pediatric patients and 20 healthy children. Macular thickness, choroidal thickness, vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) values were obtained. Central vessel and perfusion densities were measured at the central 6-mm area, and the values were compared among three subgroups according to location. RESULTS: The mean ages of patients and controls were 12. 42 ± 3.3 years and 13.35 ± 1.2 years, respectively. Significant differences were observed between the two groups in terms of inner, outer, and full VD, as well as inner and full PD. No significant differences in center VD and PD were observed between groups. Although it was not evident in analysis of choroidal values, inflammatory sites were thickened. FAZ area significantly differed between groups (p < 0.05). CONCLUSIONS: Retinal microvascularity was impaired in the acute phase of disease in recovered COVID-19 patients aged 10-15 years. However, the microvascularity impairment was subclinical. The choroid was thickened because of inflammation during the acute phase of disease. pediatric COVID-19 patients should undergo follow up via optical coherence tomography angiography to detect subclinical and asymptomatic retinal changes. Long-term follow-up studies are needed to validate these findings.


Subject(s)
COVID-19 , Photochemotherapy , Case-Control Studies , Child , Cross-Sectional Studies , Fluorescein Angiography , Humans , Perfusion , Photochemotherapy/methods , Photosensitizing Agents , Prospective Studies , Retinal Vessels/diagnostic imaging , Retrospective Studies , SARS-CoV-2 , Tomography, Optical Coherence
15.
Photodiagnosis Photodyn Ther ; 36: 102574, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1458817

ABSTRACT

Olfactory dysfunction is commonly seen in COVID-19 patients; however, little is known about the pathophysiology and management. The present study aimed to report a series of cases in which three protocols of intranasal photobiomodulation therapy (PBMT) were used for COVID-19-related olfactory dysfunction. Irrespective of the PBMT protocol, olfaction recovery was noted in all cases but with varying degrees of improvement. Although intranasal PBMT seems to be a promising therapeutic modality, more research is needed to better define effectiveness.


Subject(s)
COVID-19 , Low-Level Light Therapy , Olfaction Disorders , Photochemotherapy , Humans , Olfaction Disorders/drug therapy , Olfaction Disorders/therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , SARS-CoV-2 , Smell
16.
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
19.
Photodiagnosis Photodyn Ther ; 35: 102447, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1405835

ABSTRACT

PURPOSE: We aimed to examine the changes in choroidal stroma and vascular system due to long-term use of N95 mask in healthcare workers. METHOD: The healthcare workers included in the study were between the ages of 18-50, with best corrected visual acuity (BCVA) 10/10, spherical and cylindrical refractive errors less than 3 diopters, intraocular pressures (IOP) within normal limits, and axial lengths (AL) less than 25 mm. The choroid was imaged with enhanced depth imaging (EDI) techniques using SD-OCT. The choroidal vascularity index (CVI), total choroidal area (TA), luminal area (LA), and stromal area (SA) were measured in the subfoveal 2 mm area. Measurements were first made after wearing the N95 mask for at least 2 hours without removing it and repeated 1hour after removing, while doing office working. RESULTS: The study included 62 eyes from 62 participants (32 women [%51.61]; 30 men [%48.39]). The mean age of patients was 33.81± 8.88 years (20-50 years). The differences in subfoveal TA, LA, SA between 2 hours of N95 mask use and 1 hour after removal of the mask were statistically significant (p<0.05 for each). However, the difference in CVI between the mask use and removal of the mask was not statically significant (p=0.537) CONCLUSION: Due to CO2 retention and hemodynamic changes, choroidal vascular flow, the choroidal vascular area, and the choroidal stromal area may be affected by prolonged use of masks.


Subject(s)
N95 Respirators , Photochemotherapy , Adolescent , Adult , Choroid/diagnostic imaging , Female , Humans , Male , Middle Aged , Photochemotherapy/methods , Photosensitizing Agents , Tomography, Optical Coherence , Visual Acuity , Young Adult
20.
Viruses ; 13(8)2021 08 15.
Article in English | MEDLINE | ID: covidwho-1355053

ABSTRACT

We compared the electrostatic properties of the spike proteins (S-proteins) of three coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2, and their interactions with photosensitizers (PSs), octacationic octakis(cholinyl)zinc phthalocyanine (Zn-PcChol8+) and monocationic methylene blue (MB). We found a major common PS binding site at the connection of the S-protein stalk and head. The molecules of Zn-PcChol8+ and MB also form electrostatic encounter complexes with large area of negative electrostatic potential at the head of the S-protein of SARS-CoV-2, between fusion protein and heptad repeat 1 domain. The top of the SARS-CoV spike head demonstrates a notable area of electrostatic contacts with Zn-PcChol8+ and MB that corresponds to the N-terminal domain. The S-protein protomers of SARS-CoV-2 in "open" and "closed" conformations demonstrate different ability to attract PS molecules. In contrast with Zn-PcChol8+, MB possesses the ability to penetrate inside the pocket formed as a result of SARS-CoV-2 receptor binding domain transition into the "open" state. The existence of binding site for cationic PSs common to the S-proteins of SARS-CoV, SARS-CoV-2, and MERS-CoV creates prospects for the wide use of this type of PSs to combat the spread of coronaviruses.


Subject(s)
Choline/metabolism , Indoles/metabolism , Isoindoles/metabolism , Middle East Respiratory Syndrome Coronavirus/chemistry , Organometallic Compounds/metabolism , Photosensitizing Agents/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Zinc Compounds/metabolism , Binding Sites , Indoles/chemistry , Methylene Blue/metabolism , Models, Molecular , Molecular Dynamics Simulation , Organometallic Compounds/chemistry , Protein Conformation , Protein Domains , Protein Subunits/chemistry , SARS Virus/chemistry , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Static Electricity
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