Repurposing methylene blue in the management of COVID-19: Mechanistic aspects and clinical investigations.
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ABSTRACT:
SUBMITTER: Dabholkar N
PROVIDER: S-EPMC8352658 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged from Wuhan in China before it spread to the entire globe. It causes coronavirus disease of 2019 (COVID-19) where mostly individuals present mild symptoms, some remain asymptomatic and some show severe lung inflammation and pneumonia in the host through the induction of a marked inflammatory 'cytokine storm'. New and efficacious vaccines have been developed and put into clinical practice in record time, however, there is a still a need for effective treatments for those who are not vaccinated or remain susceptible to emerging SARS-CoV-2 variant strains. Despite this, effective therapeutic interventions against COVID-19 remain elusive. Here, we have reviewed potential drugs for COVID-19 classified on the basis of their mode of action. The mechanisms of action of each are discussed in detail to highlight the therapeutic targets that may help in reducing the global pandemic. The review was done up to July 2021 and the data was assessed through the official websites of WHO and CDC for collecting the information on the clinical trials. Moreover, the recent research papers were also assessed for the relevant data. The search was mainly based on keywords like Coronavirus, SARS-CoV-2, drugs (specific name of the drugs), COVID-19, clinical efficiency, safety profile, side-effects etc.This review outlines potential areas for future research into COVID-19 treatment strategies.
| S-EPMC8570392 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presenting as a systemic disease associated with vascular inflammation and endothelial injury. Severe forms of SARS-CoV-2 infection induce acute respiratory distress syndrome (ARDS) and there is still an ongoing debate on whether COVID-19 ARDS and its perfusion defect differs from ARDS induced by other causes. Beside pro-inflammatory cytokines (such as interleukin-1 β [IL-1β] or IL-6), several main pathological phenomena have been seen because of endothelial cell (EC) dysfunction: hypercoagulation reflected by fibrin degradation products called D-dimers, micro- and macrothrombosis and pathological angiogenesis. Direct endothelial infection by SARS-CoV-2 is not likely to occur and ACE-2 expression by EC is a matter of debate. Indeed, endothelial damage reported in severely ill patients with COVID-19 could be more likely secondary to infection of neighboring cells and/or a consequence of inflammation. Endotheliopathy could give rise to hypercoagulation by alteration in the levels of different factors such as von Willebrand factor. Other than thrombotic events, pathological angiogenesis is among the recent findings. Overexpression of different proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) or placental growth factors (PlGF) have been found in plasma or lung biopsies of COVID-19 patients. Finally, SARS-CoV-2 infection induces an emergency myelopoiesis associated to deregulated immunity and mobilization of endothelial progenitor cells, leading to features of acquired hematological malignancies or cardiovascular disease, which are discussed in this review. Altogether, this review will try to elucidate the pathophysiology of thrombotic complications, pathological angiogenesis and EC dysfunction, allowing better insight in new targets and antithrombotic protocols to better address vascular system dysfunction. Since treating SARS-CoV-2 infection and its potential long-term effects involves targeting the vascular compartment and/or mobilization of immature immune cells, we propose to define COVID-19 and its complications as a systemic vascular acquired hemopathy.
| S-EPMC8238037 | biostudies-literature
Project description:As of January 2021, SARS-CoV-2 has killed over 2 million individuals across the world. As such, there is an urgent need for vaccines and therapeutics to reduce the burden of COVID-19. Several vaccines, including mRNA, vector-based vaccines, and inactivated vaccines, have been approved for emergency use in various countries. However, the slow roll-out of vaccines and insufficient global supply remains a challenge to turn the tide of the pandemic. Moreover, vaccines are important tools for preventing the disease but therapeutic tools to treat patients are also needed. As such, since the beginning of the pandemic, repurposed FDA-approved drugs have been sought as potential therapeutic options for COVID-19 due to their known safety profiles and potential anti-viral effects. One of these drugs is ivermectin (IVM), an antiparasitic drug created in the 1970s. IVM later exerted antiviral activity against various viruses including SARS-CoV-2. In this review, we delineate the story of how this antiparasitic drug was eventually identified as a potential treatment option for COVID-19. We review SARS-CoV-2 lifecycle, the role of the nucleocapsid protein, the turning points in past research that provided initial 'hints' for IVM's antiviral activity and its molecular mechanism of action- and finally, we culminate with the current clinical findings.
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Project description: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.
| S-EPMC7409924 | biostudies-literature
Project description:As the COVID-19 pandemic is progressing, the therapeutic gaps in conventional management have highlighted the need for the integration of traditional knowledge systems with modern medicine. Ayurvedic medicines, especially Ashwagandha (Withania somnifera (L.) Dunal, WS), may be beneficial in the management of COVID-19. WS is a widely prescribed Ayurvedic botanical known as an immunomodulatory, antiviral, anti-inflammatory, and adaptogenic agent. The chemical profile and pharmacological activities of WS have been extensively reported. Several clinical studies have reported its safety for use in humans. This review presents a research synthesis of in silico, in vitro, in vivo, and clinical studies on Withania somnifera (L.) Dunal (WS) and discusses its potential for prophylaxis and management of COVID-19. We have collated the data from studies on WS that focused on viral infections (HIV, HSV, H1N1 influenza, etc.) and noncommunicable diseases (hypertension, diabetes, cancer, etc.). The experimental literature indicates that WS has the potential for 1) maintaining immune homeostasis, 2) regulating inflammation, 3) suppressing pro-inflammatory cytokines, 4) organ protection (nervous system, heart, lung, liver, and kidney), and 5) anti-stress, antihypertensive, and antidiabetic activities. Using these trends, the review presents a triangulation of Ayurveda wisdom, pharmacological properties, and COVID-19 pathophysiology ranging from viral entry to end-stage acute respiratory distress syndrome (ARDS). The review proposes WS as a potential therapeutic adjuvant for various stages of COVID-19 management. WS may also have beneficial effects on comorbidities associated with the COVID-19. However, systematic studies are needed to realize the potential of WS for improving clinical outcome of patients with COVID-19.
| S-EPMC8126694 | biostudies-literature
Project description:Since its outbreak in the last December, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread worldwide at a pandemic proportion and thus is regarded as a global public health emergency. The existing therapeutic options for COVID-19 beyond the intensive supportive care are limited, with an undefined or modest efficacy reported so far. Drug repurposing represents an enthusiastic mechanism to use approved drugs outside the scope of their original indication and accelerate the discovery of new therapeutic options. With the emergence of COVID-19, drug repurposing has been largely applied for early clinical testing. In this review, we discuss some repurposed anticancer drugs for the treatment of COVID-19, which are under investigation in clinical trials or proposed for the clinical testing.
| S-EPMC7508523 | biostudies-literature
Project description:In December 2019, a new variant of SARS-CoV emerged, the so-called acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes the new coronavirus disease (COVID-19) and has been plaguing the world owing to its unprecedented spread efficiency, which has resulted in a huge death toll. In this sense, the repositioning of approved drugs is the fastest way to an effective response to a pandemic outbreak of this scale. Considering these facts, in this review we provide a comprehensive and critical discussion on the chemical aspects surrounding the drugs currently being studied as candidates for COVID-19 therapy. We intend to provide the general chemical community with an overview on the synthetic/biosynthetic pathways related to such molecules, as well as their mechanisms of action against the evaluated viruses and some insights on the pharmacological interactions involved in each case. Overall, the review aims to present the chemical aspects of the main bioactive molecules being considered to be repositioned for effective treatment of COVID-19 in all phases, from the mildest to the most severe.
| S-EPMC7676325 | biostudies-literature
Project description:The aim of this article is to explain the clinical benefits of the growing knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to the lungs, SARS-CoV?2 can invade multiple cell types in other organs, such as the kidneys and replicate there. Important damaging pathways of the virus, such as vascular endotheliitis, thrombotic events and systemic cytokine release are still incompletely understood. Coronavirus disease 2019 (COVID-19) is a systemic disease that necessitates intensive medical care and in particular, internal medicine involvement and represents a major challenge for all disciplines of internal medicine. Among these, nephrology in particular is involved in the fight against COVID-19 in a variety of ways: urine investigations can provide indications of multiple organ involvement, endotheliitis, microthrombi and microcirculation damage, etc. Experience with low serum albumin levels and antithrombin III activity in nephrotic patients helps to point out the decreasing effects of loop diuretics and heparin to other specialist disciplines. Nephrological knowledge of the complications of hypoalbuminemia and "resistance" to diuretics must lead to an early implementation of renal replacement procedures in order to be able to prevent mechanical ventilation in COVID-19 intensive care patients with increased extracellular lung fluid. The kidneys can be used as a seismograph for severe courses of COVID-19 and nephrological knowledge can be brought to use to optimize the intensive medical care for critically ill patients. Both together have the potential to considerably reduce morbidity and mortality further.
| S-EPMC7731728 | biostudies-literature
Project description:This review deals with the relationship among nutrition, the immune system, and coronavirus disease 2019 (COVID-19). The influence of nutrients and bioactive molecules present in foodstuffs on immune system activity, the influence of COVID-19 on the nutritional status of the patients, and the dietary recommendations for hospitalized patients are addressed. Deficient nutritional status is probably due to anorexia, nausea, vomiting, diarrhea, hypoalbuminemia, hypermetabolism, and excessive nitrogen loss. There is limited knowledge regarding the nutritional support during hospital stay of COVID-19 patients. However, nutritional therapy appears as first-line treatment and should be implemented into standard practice. Optimal intake of all nutrients, mainly those playing crucial roles in immune system, should be assured through a diverse and well-balanced diet. Nevertheless, in order to reduce the risk and consequences of infections, the intakes for some micronutrients may exceed the recommended dietary allowances since infections and other stressors can reduce micronutrient status. In the case of critically ill patients, recently published guidelines are available for their nutritional management. Further, several natural bioactive compounds interact with the angiotensin-converting enzyme 2 (ACE2) receptor, the gateway for severe acute respiratory syndrome (SARS) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Natural bioactive compounds can also reduce the inflammatory response induced by SARS-CoV-2. These compounds are potential beneficial tools in the nutritional management of COVID-19 patients.
| S-EPMC7463687 | biostudies-literature
Project description:We recently reported a real-time method to measure heparin in human whole blood based on the photoacoustic change of methylene blue (MB). Intriguingly, the MB behaved unlike other "turn on" photoacoustic probes-the absorbance decreased as the photoacoustic signal increased. The underlying mechanism was not clear and motivated this study. We studied the binding mechanism of MB and heparin in water and phosphate buffer saline (PBS) with both experimental and computational methods. We found that the photoacoustic enhancement of the MB-heparin mixture was a result of MB-heparin aggregation due to charge neutralization and resulting sequestration of MB in these aggregates. The sequestration of MB in the MB-heparin aggregates led to decreased absorbance-there was simply less free dye in solution to absorb light. The highest photoacoustic signal and aggregation occurred when the number of negatively charged sulfate groups on heparin was approximately equal to the number of positively charged MB molecule. The MB-heparin aggregates dissociated when there were more sulfated groups from heparin than MB molecules because of the electrostatic repulsion between negatively charged sulfate groups. PBS facilitated MB dimer formation regardless of heparin concentration and reprecipitated free MB in aggregates due to ionic strength and ionic shielding. Further molecular dynamics experiments found that binding of heparin occurred at the sulfates and glucosamines in heparin. Phosphate ions could interact with the heparin via sodium ions to impair the MB-heparin binding. Finally, our model found 3.7-fold more MB dimerization upon addition of heparin in MB solution confirming that heparin facilitates MB aggregation. We conclude that the addition of heparin in MB decreases the absorbance of the sample because of MB-heparin aggregation leading to fewer MB molecules in solution; however, the aggregation also increases the PA intensity because the MB molecules in the MB-heparin aggregate have reduced degrees of freedom and poor heat transfer to solvent.
| S-EPMC8046596 | biostudies-literature