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1.
Transfusion ; 63(2): 288-293, 2023 02.
Article in English | MEDLINE | ID: covidwho-2193299

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unlikely to be a major transfusion-transmitted pathogen; however, convalescent plasma is a treatment option used in some regions. The risk of transfusion-transmitted infections can be minimized by implementing Pathogen Inactivation (PI), such as THERAFLEX MB-plasma and THERAFLEX UV-Platelets systems. Here we examined the capability of these PI systems to inactivate SARS-CoV-2. STUDY DESIGN AND METHODS: SARS-CoV-2 spiked plasma units were treated using the THERAFLEX MB-Plasma system in the presence of methylene blue (~0.8 µmol/L; visible light doses: 20, 40, 60, and 120 [standard] J/cm2 ). SARS-CoV-2 spiked platelet concentrates (PCs) were treated using the THERAFLEX UV-platelets system (UVC doses: 0.05, 0.10, 0.15, and 0.20 [standard] J/cm2 ). Samples were taken prior to the first and after each illumination dose, and viral infectivity was assessed using an immunoplaque assay. RESULTS: Treatment of spiked plasma with the THERAFLEX MB-Plasma system resulted in an average ≥5.03 log10 reduction in SARS-CoV-2 infectivity at one third (40 J/cm2 ) of the standard visible light dose. For the platelet concentrates (PCs), treatment with the THERAFLEX UV-Platelets system resulted in an average ≥5.18 log10 reduction in SARS-CoV-2 infectivity at the standard UVC dose (0.2 J/cm2 ). CONCLUSIONS: SARS-CoV-2 infectivity was reduced in plasma and platelets following treatment with the THERAFLEX MB-Plasma and THERAFLEX UV-Platelets systems, to the limit of detection, respectively. These PI technologies could therefore be an effective option to reduce the risk of transfusion-transmitted emerging pathogens.


Subject(s)
COVID-19 , Methylene Blue , Humans , Methylene Blue/pharmacology , SARS-CoV-2 , COVID-19/therapy , COVID-19 Serotherapy , Light , Ultraviolet Rays , Blood Platelets , Virus Inactivation
2.
Molecules ; 27(19)2022 Sep 26.
Article in English | MEDLINE | ID: covidwho-2066274

ABSTRACT

New Ni (II) and Cu (II) complexes with pyridoxal-semicarbazone were synthesized and their structures were solved by X-ray crystallography. This analysis showed the bis-ligand octahedral structure of [Ni(PLSC-H)2]·H2O and the dimer octahedral structure of [Cu(PLSC)(SO4)(H2O)]2·2H2O. Hirshfeld surface analysis was employed to determine the most important intermolecular interactions in the crystallographic structures. The structures of both complexes were further examined using density functional theory and natural bond orbital analysis. The photocatalytic decomposition of methylene blue in the presence of both compounds was investigated. Both compounds were active toward E. coli and S. aureus, with a minimum inhibition concentration similar to that of chloramphenicol. The obtained complexes led to the formation of free radical species, as was demonstrated in an experiment with dichlorofluorescein-diacetate. It is postulated that this is the mechanistic pathway of the antibacterial and photocatalytic activities. Cyclic voltammograms of the compounds showed the peaks of the reduction of metal ions. A molecular docking study showed that the Ni(II) complex exhibited promising activity towards Janus kinase (JAK), as a potential therapy for inflammatory diseases, cancers, and immunologic disorders.


Subject(s)
Coordination Complexes , Semicarbazones , Anti-Bacterial Agents/pharmacology , Chloramphenicol , Coordination Complexes/chemistry , Crystallography, X-Ray , Escherichia coli/metabolism , Janus Kinases/metabolism , Ligands , Methylene Blue , Molecular Docking Simulation , Molecular Structure , Pyridoxal , Staphylococcus aureus/metabolism , Nickel , Copper
3.
Sci Rep ; 12(1): 16038, 2022 09 26.
Article in English | MEDLINE | ID: covidwho-2050535

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causative agent of the COVID-19, which is a global pandemic, has infected more than 552 million people, and killed more than 6.3 million people. SARS-CoV-2 can be transmitted through airborne route in addition to direct contact and droplet modes, the development of disinfectants that can be applied in working spaces without evacuating people is urgently needed. TiO2 is well known with some features of the purification, antibacterial/sterilization, making it could be developed disinfectants that can be applied in working spaces without evacuating people. Facing the severe epidemic, we expect to fully expand the application of our proposed effective approach of mechanical coating technique (MCT), which can be prepared on a large-scale fabrication of an easy-to-use TiO2/Ti photocatalyst coating, with hope to curb the epidemic. The photocatalytic inactivation of SARS-CoV-2 and influenza virus, and the photocatalytic degradation of acetaldehyde (C2H4O) and formaldehyde (CH2O) has been investigated. XRD and SEM results show that anatase TiO2 successfully coats on the surface of Ti coatings, while the crystal structure of anatase TiO2 can be increased during the following oxidation in air. The catalytic activity towards methylene blue of TiO2/Ti coating balls has been significantly enhanced by the followed oxidation in air, showing a very satisfying photocatalytic degradation of C2H4O and CH2O. Notably, the TiO2/Ti photocatalyst coating balls demonstrate a significant antiviral activity, with a decrease rate of virus reached 99.96% for influenza virus and 99.99% for SARS-CoV-2.


Subject(s)
COVID-19 , Disinfectants , Acetaldehyde , Anti-Bacterial Agents , Antiviral Agents , Catalysis , Formaldehyde/chemistry , Humans , Methylene Blue/chemistry , SARS-CoV-2 , Titanium/chemistry , Titanium/pharmacology
4.
Int J Mol Sci ; 23(19)2022 Sep 24.
Article in English | MEDLINE | ID: covidwho-2043774

ABSTRACT

Coronaviruses as possible cross-species viruses have caused several epidemics. The ongoing emergency of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed severe threats to the global economy and public health, which has generated great concerns about zoonotic viruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), an alpha-coronavirus, was responsible for mass piglet deaths, resulting in unprecedented economic losses, and no approved drugs or vaccines are currently available for SADS-CoV infection. Given its potential ability to cause cross-species infection, it is essential to develop specific antiviral drugs and vaccines against SADS-CoV. Drug screening was performed on a total of 3523 compound-containing drug libraries as a strategy of existing medications repurposing. We identified five compounds (gemcitabine, mycophenolate mofetil, mycophenolic acid, methylene blue and cepharanthine) exhibiting inhibitory effects against SADS-CoV in a dose-dependent manner. Cepharanthine and methylene blue were confirmed to block viral entry, and gemcitabine, mycophenolate mofetil, mycophenolic acid and methylene blue could inhibit viral replication after SADS-CoV entry. This is the first report on SADS-CoV drug screening, and we found five compounds from drug libraries to be potential anti-SADS-CoV drugs, supporting the development of antiviral drugs for a possible outbreak of SADS-CoV in the future.


Subject(s)
Antiviral Agents , COVID-19 , Alphacoronavirus , Animals , Antiviral Agents/pharmacology , Methylene Blue , Mycophenolic Acid , SARS-CoV-2 , Swine
5.
Infect Disord Drug Targets ; 22(6): 62-65, 2022.
Article in English | MEDLINE | ID: covidwho-2022295

ABSTRACT

BACKGROUND: In COVID-19, the respiratory tract is usually affected by SARS-CoV-2 infection. Due to viral transmission in the blood and an overwhelming inflammatory response, including cytokine storm, the condition can progress to acute respiratory distress syndrome and failure. Methylene blue is the only medicine that has been shown to reduce the excessive generation of reactive species and cytokines. CASE PRESENTATION: A 51-year-old male patient came to the hospital with shortness of breath. At room air, the patient was having 70% Spo2. The patient was treated with a noninvasive ventilator (NIV) and Standard of care (SOC). Due to prolonged hypoxia and respiratory distress, the patient was treated with NIV and the methylene blue (MB) was given in a humidifier for 5 days. RESULT: Methylene blue resulted in a significant decrease in respiratory distress and a steep rise in Spo2. CONCLUSION: We suggest trying methylene blue as an additional intervention in COVID-related acute respiratory distress to avoid the disease's devastating consequences.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Male , Methylene Blue , Middle Aged , SARS-CoV-2
6.
Sci Rep ; 12(1): 14438, 2022 08 24.
Article in English | MEDLINE | ID: covidwho-2000930

ABSTRACT

The lack of therapeutic options to fight Covid-19 has contributed to the current global pandemic. Despite the emergence of effective vaccines, development of broad-spectrum antiviral treatment remains a significant challenge, in which antimicrobial photodynamic therapy (aPDT) may play a role, especially at early stages of infection. aPDT of the nares with methylene blue (MB) and non-thermal light has been successfully utilized to inactivate both bacterial and viral pathogens in the perioperative setting. Here, we investigated the effect of MB-aPDT to inactivate human betacoronavirus OC43 and SARS-CoV-2 in vitro and in a proof-of-principle COVID-19 clinical trial to test, in a variety of settings, the practicality, technical feasibility, and short-term efficacy of the method. aPDT yielded inactivation of up to 6-Logs in vitro, as measured by RT-qPCR and infectivity assay. From a photo-physics perspective, the in vitro results suggest that the response is not dependent on the virus itself, motivating potential use of aPDT for local destruction of SARS-CoV-2 and its variants. In the clinical trial we observed variable effects on viral RNA in nasal-swab samples as assessed by RT-qPCR attributed to aPDT-induced RNA fragmentation causing falsely-elevated counts. However, the viral infectivity in clinical nares swabs was reduced in 90% of samples and undetectable in 70% of samples. This is the first demonstration based on quantitative clinical viral infectivity measurements that MB-aPDT is a safe, easily delivered and effective front-line technique that can reduce local SARS-CoV-2 viral load.


Subject(s)
COVID-19 Drug Treatment , Disinfection , Nose , Photochemotherapy , Anti-Infective Agents/adverse effects , Anti-Infective Agents/pharmacology , Disinfection/methods , Feasibility Studies , Humans , Methylene Blue/adverse effects , Methylene Blue/pharmacology , Nose/virology , Pandemics , RNA, Viral/analysis , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Treatment Outcome , Viral Load/drug effects
7.
Am J Infect Control ; 50(8): 857-862, 2022 08.
Article in English | MEDLINE | ID: covidwho-2000224

ABSTRACT

BACKGROUND: Global shortage of personal protective equipment (PPE), as consequence of the COVID-19 global pandemic, has unmasked significant resource inequities prompting efforts to develop methods for safe PPE decontamination for reuse. The World Health Organization (WHO) in their Rational Use of PPE bulletin cited the use of a photodynamic dye, methylene blue, and light exposure as a viable option for N95 respirator decontamination. Because WHO noted that methylene blue (MB) would be applied to surfaces through which health care workers breathe, we hypothesized that little to no MB will be detectable by spectroscopy when the PPE is subjected to MB at supraphysiologic airflow rates. METHODS: A panel of N95 respirators, medical masks, and cloth masks were sprayed with 5 cycles of 1,000 uM MB solution. Mask coupons were subjected to the equivalent of 120 L/min of 100% humidified air flow. Effluent gas was trapped in an aqueous solution and the resultant fluid was sampled for MB absorbance with a level of detection of 0.004 mg/m3. RESULTS: No detectable MB was identified for any mask using Ultraviolet-Visible spectroscopy. CONCLUSIONS: At 500-fold the amount of MB applied to N95 respirators and medical masks as were used for the decontamination study cited in the WHO Rational Use of PPE bulletin, no detectable MB was observed, thus providing safety evidence for the use of methylene blue and light exposure for mask decontamination.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , Decontamination/methods , Equipment Reuse , Humans , Methylene Blue , N95 Respirators
8.
Am J Infect Control ; 50(8): 906-908, 2022 08.
Article in English | MEDLINE | ID: covidwho-2000223

ABSTRACT

Using the Murine Hepatitis Virus (MHV) A59 coronavirus as a SARS-CoV-2 animal surrogate, we validated that methylene blue (MB) in combination with sunlight exposure is a robust, fast, and low-cost decontamination method for PPE that should be added to the toolbox of practical pandemic preparedness.


Subject(s)
COVID-19 , Methylene Blue , Animals , COVID-19/prevention & control , Disinfection/methods , Mice , Personal Protective Equipment , SARS-CoV-2 , Sunlight
9.
Am J Infect Control ; 50(8): 863-870, 2022 08.
Article in English | MEDLINE | ID: covidwho-2000222

ABSTRACT

BACKGROUND: The COVID-19 pandemic resulted in a worldwide shortage of N95 respirators, prompting the development of decontamination methods to enable limited reuse. Countries lacking reliable supply chains would also benefit from the ability to safely reuse PPE. Methylene blue (MB) is a light-activated dye with demonstrated antimicrobial activity used to sterilize blood plasma. Decontamination of respirators using photoactivated MB requires no specialized equipment, making it attractive for use in the field during outbreaks. METHODS: We examined decontamination of N95 and KN95 respirators using photoactivated MB and 3 variants of SARS-CoV-2, the virus that causes COVID-19; and 4 World Health Organization priority pathogens: Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Lassa virus. Virus inactivation by pretreating respirator material was also tested. RESULTS: Photoactivated MB inactivated all tested viruses on respirator material, albeit with varying efficiency. Virus applied to respirator material pre-treated with MB was also inactivated, thus MB pretreatment may potentially protect respirator wearers from virus exposure in real-time. CONCLUSIONS: These results demonstrate that photoactivated MB represents a cost-effective, rapid, and widely deployable method to decontaminate N95 respirators for reuse during supply shortages.


Subject(s)
COVID-19 , Hemorrhagic Fever, Ebola , Middle East Respiratory Syndrome Coronavirus , Nipah Virus , COVID-19/prevention & control , Decontamination/methods , Equipment Reuse , Hemorrhagic Fever, Ebola/prevention & control , Humans , Methylene Blue/pharmacology , N95 Respirators , Pandemics/prevention & control , SARS-CoV-2 , Ventilators, Mechanical
10.
Am J Infect Control ; 50(8): 871-877, 2022 08.
Article in English | MEDLINE | ID: covidwho-2000219

ABSTRACT

BACKGROUND: In the context of the SARS-CoV-2 pandemic, reuse of personal protective equipment, specifically that of medical face coverings, has been recommended. The reuse of these typically single-use only items necessitates procedures to inactivate contaminating human respiratory and gastrointestinal pathogens. We previously demonstrated decontamination of surgical masks and respirators contaminated with infectious SARS-CoV-2 and various animal coronaviruses via low concentration- and short exposure methylene blue photochemical treatment (10 µM methylene blue, 30 minutes of 12,500-lux red light or 50,000 lux white light exposure). METHODS: Here, we describe the adaptation of this protocol to the decontamination of a more resistant, non-enveloped gastrointestinal virus and demonstrate efficient photodynamic inactivation of murine norovirus, a human norovirus surrogate. RESULTS: Methylene blue photochemical treatment (100 µM methylene blue, 30 minutes of 12,500-lux red light exposure) of murine norovirus-contaminated masks reduced infectious viral titers by over four orders of magnitude on surgical mask surfaces. DISCUSSION AND CONCLUSIONS: Inactivation of a norovirus, the most difficult to inactivate of the respiratory and gastrointestinal human viruses, can predict the inactivation of any less resistant viral mask contaminant. The protocol developed here thus solidifies the position of methylene blue photochemical decontamination as an important tool in the package of practical pandemic preparedness.


Subject(s)
Decontamination , Masks , Methylene Blue , Norovirus , Animals , COVID-19/prevention & control , Decontamination/methods , Equipment Reuse , Humans , Masks/virology , Methylene Blue/toxicity , Mice , SARS-CoV-2
11.
Biosens Bioelectron ; 215: 114556, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-1936098

ABSTRACT

Herein, an aptasensor was designed to detect the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2-RBD) based on the encapsulation of the methylene blue (MB) inside the mesoporous silica film (MPSF), and an aptamer as an electrochemical probe, a porous matrix, and a bio-gatekeeper, respectively. The signal analysis of the proposed aptasensor indicated that the surface coverage of the encapsulated MB inside the MPSF (MB@MPSF) was 1.9 nmol/cm2. Aptamers were capped the MB@MPSF, avoiding the release of MB into the solution via the electrostatic attraction between the positively charged amino groups of the MPSF and negatively charged phosphate groups of the aptamers. Therefore, the electrochemical signal of the encapsulated MB in the absence of the SARS-CoV-2-RBD was high. In the presence of SARS-CoV-2-RBD, the aptamers that had a high affinity to the SARS-CoV-2-RBD molecules were removed from the electrode surface to interact with SARS-CoV-2-RBD. It gave rise to the release of the MB from the MPSF to the solution and washed away on the electrode surface. Therefore, the electrochemical signal of the aptasensor decreased. The electrochemical signal was recorded with a square wave voltammetry technical in the range of 0.5-250 ng/mL of SARS-CoV-2-RBD in a saliva sample. The limit of detection was found to be 0.36 ng/mL. Furthermore, the selectivity factor values of the proposed aptasensor to 32 ng/mL SARS-CoV-2-RBD in the presence of C-reactive protein, hemagglutinin, and neuraminidase of influenza A virus were 35.9, 11.7, and 17.37, respectively, indicating the high selectivity of the proposed aptasensor.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , COVID-19 , Graphite , Aptamers, Nucleotide/chemistry , COVID-19/diagnosis , Electrochemical Techniques , Electrodes , Gold/chemistry , Graphite/chemistry , Humans , Lasers , Limit of Detection , Methylene Blue/chemistry , SARS-CoV-2 , Silicon Dioxide
12.
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
13.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1801589

ABSTRACT

Many novel drugs were used in COVID19 pandemic to improve outcome. One such molecule is Methylene blue which is a, tricyclic phenothiazine compound approved for the treatment of acquired methemoglobinemia and some other uses US FDA. This molecule was found to inhibit the interaction of COVID19 virus and target cells in dose dependent manner. It was also found to inhibit interaction of viron with host cells, by inhibiting interaction of SARS CoV2 spike protein and ACE inhibitor receptor interactions. MATERIAL AND METHODS: A) Aim & Objectives: To evaluate the effect of Nebulised Methylene blue on the clinical course and outcomes of patients with COVID-19 infections. B) Study design Observational Study C) Participants 63 COVID19 RT-PCR positive cases divided in 3 groups. Group 1 consists of patients who were prescribed Methylene blue nebulization in form of Methylene blue 0.5 mg via nebulization along with bronchodilator Levosalbutamol (1.25 mg) + Ipratropium (500 mcg) three times a day . Group 2 consists of patients with Methylene blue nebulization in form of Methylene blue 0.5 mg via nebulization along with inhalational steroid Budesonide (1 mg). Group 3 acted were those patients who had no Methylene blue nebulisation in their treatment. OBSERVATION: 1) Analysis 63 cases were divided in 3 groups of 21 each, descriptive and frequency analysis of cases in groups are shown. CONCLUSION: No statistically significant difference in outcome measures like Spo2, duration of hospital stay or inflammatory markers. A general trend of fall in inflammatory markers and O2 requirements in group receiving methylene blue but this difference was not consistantly statistically significant.


Subject(s)
COVID-19 Drug Treatment , Methemoglobinemia , Humans , Methylene Blue/pharmacology , Methylene Blue/therapeutic use , Pandemics , SARS-CoV-2
14.
Nat Prod Res ; 36(23): 6150-6155, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1764406

ABSTRACT

The interaction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) of spike protein with angiotensin-converting enzyme 2 (ACE2) mediates cell invasion. While this interaction mechanism is conserved, the RBD is affected by amino acid mutations in variants such as Delta and Omicron, resulting in enhanced transmissibility and altered ligand binding. Tanshinones are currently investigated as multi-target antiviral agents, but the studies were limited to the original SARS-CoV-2. This study aims at investigating the interaction of tanshinones with the Delta RBD. Chloroquine, methylene blue and pyronaridine, antimalarials previously identified as SARS-CoV-2 RBD binders, were studied for reference. Docking indicated the best scores for tanshinones, while bio-layer interferometry and molecular dynamics highlighted methylene blue as the best Delta RBD binder, although with decreased affinity with respect to the original strain.


Subject(s)
Antimalarials , COVID-19 Drug Treatment , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Antimalarials/pharmacology , Methylene Blue , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Binding Sites
15.
Photochem Photobiol Sci ; 21(6): 1101-1109, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1750911

ABSTRACT

The amplitude of the coronavirus disease 2019 (COVID-19) pandemic motivated global efforts to find therapeutics that avert severe forms of this illness. The urgency of the medical needs privileged repositioning of approved medicines. Methylene blue (MB) has been in clinical use for a century and proved especially useful as a photosensitizer for photodynamic disinfection (PDI). We describe the use of MB to photo-inactivate SARS-CoV-2 in samples collected from COVID-19 patients. One minute of treatment can reduce the percentage inhibition of amplification by 99.99% under conditions of low cytotoxicity. We employed a pseudotyped lentiviral vector (LVs) encoding the luciferase reporter gene and exhibiting the S protein of SARS-CoV-2 at its surface, to infect human ACE2-expressing HEK293T cells. Pre-treatment of LVs with MB-PDI prevented infection at low micromolar MB concentrations and 1 min of illumination. These results reveal the potential of MB-PDI to reduce viral loads in the nasal cavity and oropharynx in the early stages of COVID-19, which may be employed to curb the transmission and severity of the disease.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Disinfection/methods , HEK293 Cells , Humans , Methylene Blue/pharmacology
16.
Int J Mol Sci ; 23(3)2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1686814

ABSTRACT

A chabazite-type zeolite was prepared by the hydrothermal method. Before ion exchange, the chabazite was activated with ammonium chloride (NH4Cl). The ion exchange process was carried out at a controlled temperature and constant stirring to obtain ion-exchanged chabazites of Ti4+ chabazite (TiCHA), Zn2+ chabazite (ZnCHA), Cu2+ chabazite (CuCHA), Ag+ chabazite (AgCHA) and Au3+ chabazite (AuCHA). Modified chabazite samples were characterized by X-ray diffraction (XRD), scanning electron microscope equipped with energy-dispersive spectroscopy (SEM-EDS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), N2 adsorption methods and UV-visible diffuse reflectance spectroscopy (DRS). XRD results revealed that the chabazite structure did not undergo any modification during the exchange treatments. The photocatalytic activity of chabazite samples was evaluated by the degradation of methylene blue (MB) in the presence of H2O2 under ultraviolet (UV) light illumination. The photodegradation results showed a higher degradation efficiency of modified chabazites, compared to the synthesized chabazite. CuCHA showed an efficiency of 98.92% in MB degradation, with a constant of k = 0.0266 min-1 following a first-order kinetic mechanism. Then, it was demonstrated that the modified chabazites could be used for the photodegradation of dyes.


Subject(s)
Methylene Blue/chemistry , Water Pollutants, Chemical/chemistry , Zeolites/chemistry , Photolysis , Zeolites/chemical synthesis
17.
Lancet Respir Med ; 10(3): 278-288, 2022 03.
Article in English | MEDLINE | ID: covidwho-1671366

ABSTRACT

BACKGROUND: Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio ≥6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0·9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log10 copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123. FINDINGS: Between Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4·4 days (SD 1·4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1·05 [95% CI 0·78 to 1·41]). The mean change in viral load from baseline to day 7 was -2·41 log10 copies per mL (SD 1·32) with convalescent plasma and -2·32 log10 copies per mL (1·43) with placebo (crude difference -0·10 log10 copies per mL [95% CI -0·35 to 0·15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention. INTERPRETATION: Methylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded. FUNDING: Grifols, Crowdfunding campaign YoMeCorono.


Subject(s)
COVID-19 , Methylene Blue , Adult , COVID-19/therapy , COVID-19 Vaccines , Double-Blind Method , Humans , Immunization, Passive , Middle Aged , Outpatients , SARS-CoV-2 , Treatment Outcome , COVID-19 Serotherapy
18.
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
19.
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 , Severe acute respiratory syndrome-related coronavirus/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 , Severe acute respiratory syndrome-related coronavirus/drug effects
20.
PLoS One ; 16(10): e0258368, 2021.
Article in English | MEDLINE | ID: covidwho-1468173

ABSTRACT

Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implementation of high-dose iNO therapy has not been studied. Herein we aim to explore the feasibility and safety of delivering continuous high-dose iNO over an extended period of time using an in vivo animal model. Yorkshire pigs were randomized to one of the following two groups: group 1, standard ventilation; and group 2, standard ventilation + continuous iNO 160 ppm + methylene blue (MB) as intravenous bolus, whenever required, to maintain metHb <6%. Both groups were ventilated continuously for 6 hours, then the animals were weaned from sedation, mechanical ventilation and followed for 3 days. During treatment, and on the third post-operative day, physiologic assessments were performed to monitor lung function and other significative markers were assessed for potential pulmonary or systemic injury. No significant change in lung function, or inflammatory markers were observed during the study period. Both gas exchange function, lung tissue cytokine analysis and histology were similar between treated and control animals. During treatment, levels of metHb were maintained <6% by administration of MB, and NO2 remained <5 ppm. Additionally, considering extrapulmonary effects, no significant changes were observed in biochemistry markers. Our findings showed that high-dose iNO delivered continuously over 6 hours with adjuvant MB is clinically feasible and safe. These findings support the development of investigations of continuous high-dose iNO treatment of respiratory tract infections, including SARS-CoV-2.


Subject(s)
Anti-Infective Agents/administration & dosage , Nitric Oxide/administration & dosage , Administration, Inhalation , Animals , Cytokines/analysis , Cytokines/blood , Drug Evaluation, Preclinical , Hemodynamics , Hemoglobin A/analysis , Lung/metabolism , Lung/pathology , Male , Methemoglobin/analysis , Methylene Blue/administration & dosage , Models, Animal , Nitrates/analysis , Nitrites/analysis , Swine
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