Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
1.
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
2.
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
3.
Sci Rep ; 11(1): 14295, 2021 07 12.
Article in English | MEDLINE | ID: covidwho-1387482

ABSTRACT

Methylene blue is an FDA (Food and Drug Administration) and EMA (European Medicines Agency) approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. In this study, we first evaluated the virucidal activity of methylene blue against influenza virus H1N1 upon different incubation times and in the presence or absence of light activation, and then against SARS-CoV-2. We further assessed the therapeutic activity of methylene blue by administering it to cells previously infected with SARS-CoV-2. Finally, we examined the effect of co-administration of the drug together with immune serum. Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against influenza virus H1N1 and SARS-CoV-2 at low micromolar concentrations and in the absence of UV-activation. We also confirm that MB antiviral activity is based on several mechanisms of action as the extent of genomic RNA degradation is higher in presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive and/or therapeutic efficacy against both influenza virus H1N1 and SARS-CoV-2 infections.


Subject(s)
COVID-19/drug therapy , Influenza, Human/drug therapy , Methylene Blue/pharmacology , Virus Inactivation/drug effects , Animals , COVID-19/genetics , COVID-19/virology , Chlorocebus aethiops , Humans , Influenza, Human/genetics , Influenza, Human/virology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Ultraviolet Rays/adverse effects , Vero Cells , Virus Inactivation/radiation effects , Virus Replication/drug effects , Virus Replication/radiation effects
4.
Biomed Pharmacother ; 142: 112023, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1347502

ABSTRACT

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the most recent coronaviruses, which has infected humans, and caused the disease COVID-19. The World Health Organization has declared COVID-19 as a pandemic in March 2020. The SARS-CoV-2 enters human hosts majorly via the respiratory tract, affecting the lungs first. In few critical cases, the infection progresses to failure of the respiratory system known as acute respiratory distress syndrome acute respiratory distress syndrome may be further associated with multi-organ failure and vasoplegic shock. Currently, the treatment of COVID-19 involves use of antiviral and anti-cytokine drugs. However, both the drugs have low efficacy because they cannot inhibit the production of free radicals and cytokines at the same time. Recently, some researchers have reported the use of methylene blue (MB) in COVID-19 management. MB has been used since a long time as a therapeutic agent, and has been approved by the US FDA for the treatment of other diseases. The additional advantage of MB is its low cost. MB is a safe drug when used in the dose of < 2 mg/kg. In this review, the applicability of MB in COVID-19 and its mechanistic aspects have been explored and compiled. The clinical studies have been explained in great detail. Thus, the potential of MB in the management of COVID-19 has been examined.


Subject(s)
COVID-19 , Drug Repositioning/methods , Methylene Blue/pharmacology , SARS-CoV-2 , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/virology , Enzyme Inhibitors/pharmacology , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/physiology
5.
BMC Infect Dis ; 21(1): 357, 2021 Apr 16.
Article in English | MEDLINE | ID: covidwho-1315854

ABSTRACT

BACKGROUND: In 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma. METHODS: The SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 µM. The "BX-1 AIDS treatment instrument" was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR. RESULTS: BX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL. CONCLUSION: BX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.


Subject(s)
Blood Safety , COVID-19/prevention & control , COVID-19/therapy , Methylene Blue/pharmacology , SARS-CoV-2/drug effects , Virus Inactivation , Animals , Blood Transfusion , Chlorocebus aethiops , Humans , Immunization, Passive , Plasma/virology , RNA, Viral , Vero Cells
6.
BMC Infect Dis ; 21(1): 357, 2021 Apr 16.
Article in English | MEDLINE | ID: covidwho-1190056

ABSTRACT

BACKGROUND: In 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma. METHODS: The SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 µM. The "BX-1 AIDS treatment instrument" was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR. RESULTS: BX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL. CONCLUSION: BX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.


Subject(s)
Blood Safety , COVID-19/prevention & control , COVID-19/therapy , Methylene Blue/pharmacology , SARS-CoV-2/drug effects , Virus Inactivation , Animals , Blood Transfusion , Chlorocebus aethiops , Humans , Immunization, Passive , Plasma/virology , RNA, Viral , Vero Cells
7.
Photodiagnosis Photodyn Ther ; 33: 102112, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1137557

ABSTRACT

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


Subject(s)
Methylene Blue/pharmacology , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , SARS-CoV-2/drug effects , Animals , Chlorocebus aethiops , Dose-Response Relationship, Drug , Drug Combinations , Microbiological Techniques , Porphyrins , Vero Cells
8.
Med Hypotheses ; 146: 110455, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-969218

ABSTRACT

SARS-CoV-2 infection generally begins in the respiratory tract where it can cause bilateral pneumonia. The disease can evolve into acute respiratory distress syndrome and multi-organ failure, due to viral spread in the blood and an excessive inflammatory reaction including cytokine storm. Antiviral and anti-cytokine drugs have proven to be poorly or in-effective in stopping disease progression, and mortality or serious chronic damage is common in severely ill cases. The low efficacy of antiviral drugs is probably due to late administration, when the virus has triggered the inflammatory reaction and is no longer the main protagonist. The relatively poor efficacy of anti-cytokine drugs is explained by the fact that they act on one or a few of the dozens of cytokines involved, and because other mediators of inflammation - reactive oxygen and nitrogen species - are not targeted. When produced in excess, reactive species cause extensive cell and tissue damage. The only drug known to inhibit the excessive production of reactive species and cytokines is methylene blue, a low-cost dye with antiseptic properties used effectively to treat malaria, urinary tract infections, septic shock, and methaemoglobinaemia. We propose testing methylene blue to contrast Covid-related acute respiratory distress syndrome, but particularly suggest testing it early in Covid infections to prevent the hyper-inflammatory reaction responsible for the serious complications of the disease.


Subject(s)
COVID-19/drug therapy , Methylene Blue/pharmacology , Models, Biological , Antiviral Agents/pharmacology , COVID-19/complications , COVID-19/physiopathology , Cytokines/antagonists & inhibitors , Endothelium, Vascular/drug effects , Endothelium, Vascular/injuries , Humans , Multiple Organ Failure/etiology , Multiple Organ Failure/prevention & control , Pandemics , Reactive Oxygen Species/antagonists & inhibitors , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/prevention & control , SARS-CoV-2 , Treatment Failure
9.
Int J Antimicrob Agents ; 56(6): 106202, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-866723

ABSTRACT

In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus diseases 2019 (COVID-19) emerged in Wuhan, China. Currently there is no antiviral treatment recommended against SARS-CoV-2. Identifying effective antiviral drugs is urgently required. Methylene blue has already demonstrated in vitro antiviral activity in photodynamic therapy as well as antibacterial, antifungal and antiparasitic activities in non-photodynamic assays. In this study. non-photoactivated methylene blue showed in vitro activity at very low micromolar range with an EC50 (median effective concentration) of 0.30 ± 0.03 µM and an EC90 (90% effective concentration) of 0.75 ± 0.21 µM at a multiplicity of infection (MOI) of 0.25 against SARS-CoV-2 (strain IHUMI-3). The EC50 and EC90 values for methylene blue are lower than those obtained for hydroxychloroquine (1.5 µM and 3.0 µM) and azithromycin (20.1 µM and 41.9 µM). The ratios Cmax/EC50 and Cmax/EC90 in blood for methylene blue were estimated at 10.1 and 4.0, respectively, following oral administration and 33.3 and 13.3 following intravenous administration. Methylene blue EC50 and EC90 values are consistent with concentrations observed in human blood. We propose that methylene blue is a promising drug for treatment of COVID-19. In vivo evaluation in animal experimental models is now required to confirm its antiviral effects on SARS-CoV-2. The potential interest of methylene blue to treat COVID-19 needs to be confirmed by prospective comparative clinical studies.


Subject(s)
COVID-19/drug therapy , Methylene Blue/pharmacology , SARS-CoV-2/drug effects , Virus Replication/drug effects , Animals , Chlorocebus aethiops , SARS-CoV-2/physiology , Vero Cells
10.
Med Hypotheses ; 144: 110163, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-716871

ABSTRACT

In this paper, we raise the hypothesis that Methylene Blue may be a treatment option for Corona Virus Disease of 2019 specially when combined with Non Steroid Anti-Inflammatory Drugs. In previous publications including ours, the role of kininogen system has been postulated. A correlation between clinical findings of the disease and this mechanism has been drawn to denote a pivotal role of kininogen-kallikrein system in pathophysiology of the disease. Therein the possible role of Icatibant, Ecallantide and Aprotinin in the treatment of this disease has been raised. Here we want to emphasize on an important post-receptor mechanism of bradykinin that is Nitric Oxide. We came to this aim because we found out how access to these novel treatment nominees may be expensive and unaffordable. For this reason we are focusing on possible role of an old albeit "mysterious" drug namely Methylene Blue. This medication may abort effects of Bradykinin by inhibition of Nitric Oxide synthase inhibitor and promote oxygen saturation while it is inexpensive and ubiquitously accessible. Clinical studies cannot be over emphasized.


Subject(s)
COVID-19/drug therapy , Methylene Blue/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Aprotinin/pharmacology , Bradykinin/analogs & derivatives , Bradykinin/metabolism , Bradykinin/pharmacology , Cytokines/metabolism , Humans , Kininogens/metabolism , Models, Theoretical , Nitric Oxide/metabolism , Peptides/pharmacology , Renin-Angiotensin System
SELECTION OF CITATIONS
SEARCH DETAIL