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1.
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
2.
Environ Sci Technol ; 56(7): 4295-4304, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1735181

ABSTRACT

To address the challenge of the airborne transmission of SARS-CoV-2, photosensitized electrospun nanofibrous membranes were fabricated to effectively capture and inactivate coronavirus aerosols. With an ultrafine fiber diameter (∼200 nm) and a small pore size (∼1.5 µm), optimized membranes caught 99.2% of the aerosols of the murine hepatitis virus A59 (MHV-A59), a coronavirus surrogate for SARS-CoV-2. In addition, rose bengal was used as the photosensitizer for membranes because of its excellent reactivity in generating virucidal singlet oxygen, and the membranes rapidly inactivated 97.1% of MHV-A59 in virus-laden droplets only after 15 min irradiation of simulated reading light. Singlet oxygen damaged the virus genome and impaired virus binding to host cells, which elucidated the mechanism of disinfection at a molecular level. Membrane robustness was also evaluated, and in general, the performance of virus filtration and disinfection was maintained in artificial saliva and for long-term use. Only sunlight exposure photobleached membranes, reduced singlet oxygen production, and compromised the performance of virus disinfection. In summary, photosensitized electrospun nanofibrous membranes have been developed to capture and kill airborne environmental pathogens under ambient conditions, and they hold promise for broad applications as personal protective equipment and indoor air filters.


Subject(s)
COVID-19 , Nanofibers , Animals , COVID-19/prevention & control , Disinfection , Light , Mice , SARS-CoV-2
3.
Int J Mol Sci ; 23(4)2022 Feb 12.
Article in English | MEDLINE | ID: covidwho-1715397

ABSTRACT

The state of red blood cells (RBCs) and their functional possibilities depend on the structural organization of the membranes. Cell morphology and membrane nanostructure are compositionally and functionally related to the cytoskeleton network. In this work, the influence of agents (hemin, endogenous oxidation during storage of packed RBCs, ultraviolet (UV) radiation, temperature, and potential of hydrogen (pH) changes) on the relationships between cytoskeleton destruction, membrane nanostructure, and RBC morphology was observed by atomic force microscope. It was shown that the influence of factors of a physical and biochemical nature causes structural rearrangements in RBCs at all levels of organization, forming a unified mechanism of disturbances in relationships "cytoskeleton-membrane nanosurface-cell morphology". Filament ruptures and, consequently, large cytoskeleton pores appeared. The pores caused membrane topological defects in the form of separate grain domains. Increasing loading doses led to an increase in the number of large cytoskeleton pores and defects and their fusion at the membrane nanosurfaces. This caused the changes in RBC morphology. Our results can be used in molecular cell biology, membrane biophysics, and in fundamental and practical medicine.


Subject(s)
Cell Membrane/ultrastructure , Cytoskeleton/ultrastructure , Erythrocytes/pathology , Adult , Cells, Cultured , Erythrocytes/drug effects , Erythrocytes/radiation effects , Female , Hemin/toxicity , Humans , Hydrogen-Ion Concentration , Light/adverse effects , Male , Middle Aged , Oxidants/toxicity
4.
J Photochem Photobiol B ; 229: 112415, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1712830

ABSTRACT

Noscapine (NSC) is a benzyl-isoquinoline alkaloid discovered in 1930 as an antitussive agent. Recently, NSC has also been reported to exhibit antitumor activity and, according to computational studies, it is able to attack the protease enzyme of Coronavirus (COVID-19) and thus could be used as antiviral for COVID-19 pandemic. Therefore, an increasing use of this drug could be envisaged in the coming years. NSC is readily metabolized with a half-life of 4.5 h giving rise to cotarnine, hydrocotarnine, and meconine, arising from the oxidative breaking of the CC bond between isoquinoline and phthalide moieties. Because of its potentially increasing use, high concentrations of NSC but also its metabolites will be delivered in the environment and potentially affect natural ecosystems. Thus, the aim of this work is to investigate the degradation of NSC in the presence of naturally occurring photocatalysts. As a matter of fact, the present contribution has demonstrated that NSC can be efficiently degraded in the presence of a derivative of the natural organic dye Riboflavin (RFTA) upon exposure to visible light. Indeed, a detailed study of the mechanism involved in the photodegradation revealed the similarities between the biomimetic and the photocatalyzed processes. In fact, the main photoproducts of NSC were identified as cotarnine and opianic acid based on a careful UPLC-MS2 analysis compared to the independently synthesized standards. The former is coincident with one of the main metabolites obtained in humans, whereas the latter is related to meconine, a second major metabolite of NSC. Photophysical experiments demonstrated that the observed oxidative cleavage is mediated mainly by singlet oxygen in a medium in which the lifetime of 1O2 is long enough, or by electron transfer to the triplet excited state of RFTA if the photodegradation occurs in aqueous media, where the 1O2 lifetime is very short.


Subject(s)
COVID-19 , Environmental Restoration and Remediation , Noscapine , Biomimetics , Chromatography, Liquid , Coloring Agents , Ecosystem , Humans , Light , Pandemics , Photolysis , Riboflavin/chemistry , Tandem Mass Spectrometry , Water/chemistry
5.
Sci Rep ; 12(1): 1724, 2022 02 02.
Article in English | MEDLINE | ID: covidwho-1699378

ABSTRACT

This study introduces localized surface plasmon resonance (L-SPR) mediated heating filter membrane (HFM) for inactivating universal viral particles by using the photothermal effect of plasmonic metal nanoparticles (NPs). Plasmonic metal NPs were coated onto filter membrane via a conventional spray-coating method. The surface temperature of the HFM could be controlled to approximately 40-60 °C at room temperature, owing to the photothermal effect of the gold (Au) NPs coated on them, under irradiation by visible light-emitting diodes. Due to the photothermal effect of the HFMs, the virus titer of H1Npdm09 was reduced by > 99.9%, the full inactivation time being < 10 min, confirming the 50% tissue culture infective dose (TCID50) assay. Crystal violet staining showed that the infectious samples with photothermal inactivation lost their infectivity against Mardin-Darby Canine Kidney cells. Moreover, photothermal inactivation could also be applied to reduce the infectivity of SARS-CoV-2, showing reduction rate of 99%. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques to confirm the existence of viral genes on the surface of the HFM. The results of the TCID50 assay, crystal violet staining method, and qRT-PCR showed that the effective and immediate reduction in viral infectivity possibly originated from the denaturation or deformation of membrane proteins and components. This study provides a new, simple, and effective method to inactivate viral infectivity, leading to its potential application in various fields of indoor air quality control and medical science.


Subject(s)
COVID-19/virology , Hot Temperature , Light , Metal Nanoparticles , Micropore Filters , SARS-CoV-2 , Surface Plasmon Resonance/methods , Virion , Virus Inactivation , Air Pollution, Indoor , Animals , Cells, Cultured , Dogs , Gold/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity
6.
J Photochem Photobiol B ; 228: 112405, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1665224

ABSTRACT

Our exposure to blue light from artificial sources such as indoor lights (mainly light-emitting diodes [LEDs]) and electronic devices (e.g., smartphones, computer monitors, and television screens), has increased in recent years, particularly during the recent coronavirus disease 2019 lockdown. This radiation has been associated to skin damage across its potential in generating reactive oxygen species in both the epidermis and the dermis, skin water imbalances and of potential activating melanin production. These circumstances make it important to determine whether current blue light exposure levels under artificial illumination and electronic devices exposure can cause the previously indicated disorders as compared to solar UV and visible radiation in a typical summer day. Blue light accounted for 25% of the sun's rays, approximately 30% of radiation emitted by electronic devices, and approximately from 6% to 40% of that emitted by indoor lights. The reference equations showed that the sun was the main source of effective irradiance for immediate and persistent pigmentation as well as for potential oxidative stress in our skin. Effective blue light exposure to artificial devices is significantly lower than the solar contribution. However, its contribution must be considered as accumulative dose effect, and especially in people with hypersensitivity promoting skin hyperpigmentation.


Subject(s)
Light , Melanins/metabolism , Oxidative Stress/radiation effects , Ultraviolet Rays , Electronics , Humans , Skin Pigmentation/radiation effects
7.
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
8.
ACS Appl Mater Interfaces ; 14(4): 4892-4898, 2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1633913

ABSTRACT

This paper presents results of a study of a new cationic oligomer that contains end groups and a chromophore affording inactivation of SARS-CoV-2 by visible light irradiation in solution or as a solid coating on paper wipes and glass fiber filtration substrates. A key finding of this study is that the cationic oligomer with a central thiophene ring and imidazolium charged groups gives outstanding performance in both the killing of E. coli bacterial cells and inactivation of the virus at very short times. Our introduction of cationic N-methyl imidazolium groups enhances the light activation process for both E. coli and SARS-CoV-2 but dampens the killing of the bacteria and eliminates the inactivation of the virus in the dark. For the studies with this oligomer in solution at a concentration of 1 µg/mL and E. coli, we obtain 3 log killing of the bacteria with 10 min of irradiation with LuzChem cool white lights (mimicking indoor illumination). With the oligomer in solution at a concentration of 10 µg/mL, we observe 4 log inactivation (99.99%) in 5 min of irradiation and total inactivation after 10 min. The oligomer is quite active against E. coli on oligomer-coated paper wipes and glass fiber filter supports. The SARS-CoV-2 is also inactivated by oligomer-coated glass fiber filter papers. This study indicates that these oligomer-coated materials may be very useful as wipes and filtration materials.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/therapy , SARS-CoV-2/radiation effects , COVID-19/genetics , COVID-19/virology , Cations/pharmacology , Escherichia coli/drug effects , Escherichia coli/radiation effects , Humans , Light , Phototherapy , SARS-CoV-2/pathogenicity , Ultraviolet Rays , Virus Inactivation/drug effects , Virus Inactivation/radiation effects
9.
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
10.
Adv Sci (Weinh) ; 9(2): e2103240, 2022 01.
Article in English | MEDLINE | ID: covidwho-1508603

ABSTRACT

The outbreak of 2019 coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic. Despite intensive research, the current treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS-CoV-2. The NP is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with high-affinity neutralizing antibodies. The multifunctional NP efficiently captures SARS-CoV-2 pseudovirions and completely blocks viral infection to host cells in vitro through the surface neutralizing antibodies. In addition to virus capture and blocking function, the NP also possesses photothermal function to generate heat following irradiation for inactivation of virus. Importantly, the NPs described herein significantly outperform neutralizing antibodies at treating authentic SARS-CoV-2 infection in vivo. This multifunctional NP provides a flexible platform that can be readily adapted to other SARS-CoV-2 antibodies and extended to novel therapeutic proteins, thus it is expected to provide a broad range of protection against original SARS-CoV-2 and its variants.


Subject(s)
Antibodies, Neutralizing/administration & dosage , Antibodies, Viral/administration & dosage , COVID-19/therapy , Immunoconjugates/administration & dosage , Nanoparticles , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/physiology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , Antigen-Antibody Reactions , COVID-19/immunology , COVID-19/virology , Drug Evaluation, Preclinical , Hot Temperature , Humans , Immunoconjugates/immunology , Immunoconjugates/therapeutic use , Light , Mice , Nanoparticles/therapeutic use , Phosphatidylethanolamines , Polyethylene Glycols , Polymers , Receptors, Virus/physiology , Semiconductors , Spike Glycoprotein, Coronavirus/immunology , Thiadiazoles , Virus Inactivation
11.
Vox Sang ; 115(3): 146-151, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-1508355

ABSTRACT

BACKGROUND: Emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV), Crimean-Congo haemorrhagic fever virus (CCHFV) and Nipah virus (NiV) have been identified to pose a potential threat to transfusion safety. In this study, the ability of the THERAFLEX UV-Platelets and THERAFLEX MB-Plasma pathogen inactivation systems to inactivate these viruses in platelet concentrates and plasma, respectively, was investigated. MATERIALS AND METHODS: Blood products were spiked with SARS-CoV, CCHFV or NiV, and then treated with increasing doses of UVC light (THERAFLEX UV-Platelets) or with methylene blue (MB) plus increasing doses of visible light (MB/light; THERAFLEX MB-Plasma). Samples were taken before and after treatment with each illumination dose and tested for residual infectivity. RESULTS: Treatment with half to three-fourths of the full UVC dose (0·2 J/cm2 ) reduced the infectivity of SARS-CoV (≥3·4 log), CCHFV (≥2·2 log) and NiV (≥4·3 log) to the limit of detection (LOD) in platelet concentrates, and treatment with MB and a fourth of the full light dose (120 J/cm2 ) decreased that of SARS-CoV (≥3·1 log), CCHFV (≥3·2 log) and NiV (≥2·7 log) to the LOD in plasma. CONCLUSION: Our study demonstrates that both THERAFLEX UV-Platelets (UVC) and THERAFLEX MB-Plasma (MB/light) effectively reduce the infectivity of SARS-CoV, CCHFV and NiV in platelet concentrates and plasma, respectively.


Subject(s)
Hemorrhagic Fever Virus, Crimean-Congo/radiation effects , Light , Methylene Blue/pharmacology , Nipah Virus/radiation effects , SARS Virus/radiation effects , Ultraviolet Rays , Virus Inactivation , Blood Platelets/virology , Blood Transfusion , Hemorrhagic Fever Virus, Crimean-Congo/drug effects , Humans , Nipah Virus/drug effects , Plasma/virology , SARS Virus/drug effects
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.
Sci Rep ; 11(1): 20877, 2021 10 22.
Article in English | MEDLINE | ID: covidwho-1479811

ABSTRACT

Adenovirus vectors offer a platform technology for vaccine development. The value of the platform has been proven during the COVID-19 pandemic. Although good stability at 2-8 °C is an advantage of the platform, non-cold-chain distribution would have substantial advantages, in particular in low-income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving excellent recovery of adenovirus-vectored vaccines after storage at temperatures as high as 45 °C. This matrix is, however, prone to fragmentation and so not suitable for clinical translation. Here, we report an investigation of alternative fibrous matrices which might be suitable for clinical use. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components, finding that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to identify a potentially biocompatible matrix with encouraging performance. We discuss remaining challenges for transfer of the technology into clinical use, including reliability of process performance.


Subject(s)
Adenoviridae/genetics , Adenovirus Vaccines/chemistry , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Vaccine Potency , Adenoviruses, Simian , Biocompatible Materials , Calorimetry, Differential Scanning , Glass , HEK293 Cells , Humans , Light , Magnetic Resonance Spectroscopy , Materials Testing , Microscopy, Confocal , Microscopy, Electron, Scanning , Polyvinyl Alcohol , Rabies Vaccines , Scattering, Radiation , Spectroscopy, Fourier Transform Infrared , Sugars/chemistry , Temperature , Thermogravimetry , Trehalose/chemistry
15.
Sci Rep ; 11(1): 20595, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1475487

ABSTRACT

The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that primary 3D human tracheal/bronchial-derived epithelial tissues tolerated high doses of a narrow spectral band of visible light centered at a peak wavelength of 425 nm. We extended these studies to Vero E6 cells to understand how light may influence the viability of a mammalian cell line conventionally used for assaying SARS-CoV-2. The exposure of single-cell monolayers of Vero E6 cells to similar doses of 425 nm blue light resulted in viabilities that were dependent on dose and cell density. Doses of 425 nm blue light that are well-tolerated by Vero E6 cells also inhibited infection and replication of cell-associated SARS-CoV-2 by > 99% 24 h post-infection after a single five-minute light exposure. Moreover, the 425 nm blue light inactivated cell-free betacoronaviruses including SARS-CoV-1, MERS-CoV, and SARS-CoV-2 up to 99.99% in a dose-dependent manner. Importantly, clinically applicable doses of 425 nm blue light dramatically inhibited SARS-CoV-2 infection and replication in primary human 3D tracheal/bronchial tissue. Safe doses of visible light should be considered part of the strategic portfolio for the development of SARS-CoV-2 therapeutic countermeasures to mitigate coronavirus disease 2019 (COVID-19).


Subject(s)
COVID-19/drug therapy , COVID-19/prevention & control , Light , SARS-CoV-2 , Trachea/radiation effects , Virus Replication/radiation effects , Adult , Animals , Antiviral Agents/pharmacology , Bronchi , Calibration , Cell-Free System , Chlorocebus aethiops , Epithelium/pathology , Female , Humans , Respiratory Mucosa/radiation effects , Trachea/virology , Vero Cells
16.
ACS Appl Mater Interfaces ; 13(42): 49754-49761, 2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1475248

ABSTRACT

A reliable and sensitive detection approach for SARS-CoV 2 is essential for timely infection diagnosis and transmission prevention. Here, a two-dimensional (2D) metal-organic framework (MOF)-based photoelectrochemical (PEC) aptasensor with high sensitivity and stability for SARS-CoV 2 spike glycoprotein (S protein) detection was developed. The PEC aptasensor was constructed by a plasmon-enhanced photoactive material (namely, Au NPs/Yb-TCPP) with a specific DNA aptamer against S protein. The Au NPs/Yb-TCPP fabricated by in situ growth of Au NPs on the surface of 2D Yb-TCPP nanosheets showed a high electron-hole (e-h) separation efficiency due to the enhancement effect of plasmon, resulting in excellent photoelectric performance. The modified DNA aptamer on the surface of Au NPs/Yb-TCPP can bind with S protein with high selectivity, thus decreasing the photocurrent of the system due to the high steric hindrance and low conductivity of the S protein. The established PEC aptasensor demonstrated a highly sensitive detection for S protein with a linear response range of 0.5-8 µg/mL with a detection limit of 72 ng/mL. This work presented a promising way for the detection of SARS-CoV 2, which may conduce to the impetus of clinic diagnostics.


Subject(s)
Aptamers, Nucleotide/chemistry , Biosensing Techniques/methods , Metal-Organic Frameworks/chemistry , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/analysis , Base Sequence , Biosensing Techniques/instrumentation , COVID-19/diagnosis , DNA/chemistry , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Electrodes , Gold/chemistry , Gold/radiation effects , Humans , Immobilized Nucleic Acids/chemistry , Light , Limit of Detection , Metal Nanoparticles/chemistry , Metal Nanoparticles/radiation effects , Pharynx/virology , Photochemical Processes , Porphyrins/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Ytterbium/chemistry
17.
Sci Rep ; 11(1): 19470, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1447318

ABSTRACT

The germicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV associated polymer degradation limit their use in occupied spaces. Alternatively, longer wavelengths with less irradiation energy such as visible light (405 nm) have largely been explored in the context of bactericidal and fungicidal applications. Such studies indicated that 405 nm mediated inactivation is caused by the absorbance of porphyrins within the organism creating reactive oxygen species which result in free radical damage to its DNA and disruption of cellular functions. The virucidal potential of visible-light based technologies has been largely unexplored and speculated to be ineffective given the lack of porphyrins in viruses. The current study demonstrated increased susceptibility of lipid-enveloped respiratory pathogens of importance such as SARS-CoV-2 (causative agent of COVID-19) and influenza A virus to 405 nm, visible light in the absence of exogenous photosensitizers thereby indicating a potential alternative porphyrin-independent mechanism of visible light mediated viral inactivation. These results were obtained using less than expected irradiance levels which are considered safe for humans and commercially achievable. Our results support further exploration of the use of visible light technology for the application of continuous decontamination in occupied areas within hospitals and/or infectious disease laboratories, specifically for the inactivation of respiratory pathogens such as SARS-CoV-2 and Influenza A.


Subject(s)
Disinfection/methods , Influenza A Virus, H1N1 Subtype/radiation effects , SARS-CoV-2/radiation effects , Disinfection/instrumentation , Dose-Response Relationship, Radiation , Encephalomyocarditis virus/radiation effects , Light , Time Factors , Virus Inactivation/radiation effects
18.
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.
BMC Res Notes ; 14(1): 187, 2021 May 17.
Article in English | MEDLINE | ID: covidwho-1388822

ABSTRACT

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.


Subject(s)
COVID-19 , Ultraviolet Rays , Antiviral Agents , Humans , Light , SARS-CoV-2 , Virus Inactivation
20.
Int J Mol Sci ; 22(16)2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1360773

ABSTRACT

The current SARS-CoV-2 pandemic causes serious public health, social, and economic issues all over the globe. Surface transmission has been claimed as a possible SARS-CoV-2 infection route, especially in heavy contaminated environmental surfaces, including hospitals and crowded public places. Herein, we studied the deactivation of SARS-CoV-2 on photoactive AgNPs@TiO2 coated on industrial ceramic tiles under dark, UVA, and LED light irradiations. SARS-CoV-2 inactivation is effective under any light/dark conditions. The presence of AgNPs has an important key to limit the survival of SARS-CoV-2 in the dark; moreover, there is a synergistic action when TiO2 is decorated with Ag to enhance the virus photocatalytic inactivation even under LED. The radical oxidation was confirmed as the the central mechanism behind SARS-CoV-2 damage/inactivation by ESR analysis under LED light. Therefore, photoactive AgNPs@TiO2 ceramic tiles could be exploited to fight surface infections, especially during viral severe pandemics.


Subject(s)
Ceramics/chemistry , Metal Nanoparticles/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/radiation effects , Titanium/chemistry , Antiviral Agents/pharmacology , COVID-19/virology , Humans , Light , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Pandemics , Particle Size , SARS-CoV-2/metabolism , Surface Properties , Virus Inactivation/drug effects , Virus Inactivation/radiation effects
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