Methylene Blue for treating COVID-19 | Research So Far

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SARS-CoV-2, also known as coronavirus and the most recent of the seven coronaviruses (CoVs) to infect humans, is responsible for COVID-19, which the World Health Organization declared a pandemic in March 2020 and is still spreading globally. The SARS-CoV-2 virus is the most contagious agent in a century, infecting billions of people and killing millions. COVID-19 is caused by SARS-corona virus (CoV-2). The first breakout occurred towards the end of 2019, bringing symptoms such as fever and pneumonia. In severe situations, the patient dies. As of early March 2021, the COVID-19 outbreak has spread to all continents, posing a threat to global public health.

Scientific Community’s take on Corona Virus

Since the outbreak of the deadly Corona Virus, all efforts in the scientific community have been aimed at understanding the pathophysiology of the virus, as well as taking into account all elements of a global health concern and its complexity.

Many experiments were conducted to identify potential SMIs for PPIs. Scientists initiated a screen of such compounds for their ability to inhibit the interaction between SARS-CoV-2 spike protein and its high-affinity receptor ACE2, which is the first critical step that initiates the viral attachment and entry of this CoV. Methylene blue, a tricyclic phenothiazine chemical authorized for the treatment of acquired methemoglobinemia and other applications, was discovered to block this interaction.

In one of the articles published by biomedcentral.com on April 16, 2021, (Article 357) Methylene blue photochemical treatment as a reliable SARS-CoV-2 plasma virus inactivation method for blood safety and convalescent plasma therapy for COVID-19, we found that Methylene blue (MB) is added to blood products before being exposed to visible light to destroy viruses using photochemical techniques. Methylene blue has a maximum absorption peak of 670 nm and is a photosensitizer. It is typically used to treat methemoglobinemia and cyanide toxicity induced by nitrite poisoning. The surface of MB is positively charged. It may be incorporated in DNA or RNA, particularly when combined with negatively charged G-C base pairs from viral nucleic acids. Under visible light, MB absorbs light energy, converts it from the ground state to a single state, and creates singlet oxygen via electron transfer, which destroys and breaks nucleic acids, allowing viruses to be killed. BX-1-based MB photochemical technique has the capacity to efficiently inactivate SARS-CoV-2 and has significant promise for guaranteeing the safety of blood transfusions, plasma transfusion treatment in recovering patients, and the preparation of inactivated vaccines.

Role of Methylene Blue in treatment of Covid-19

 In the article published by NCBI on Aug 6, 2020, Methylene blue may have a role in the treatment of COVID-19, they raised the opinion that Methylene Blue might be a treatment option for Corona Virus.

In medicine, there have traditionally been well-known indications for Methylene Blue. Methylene Blue is a phenothiazine derivative. It is a well-known treatment for methemoglobinemia that converts ferric iron in methemoglobin to ferrous iron in normal haemoglobin at dosages of 1–2 mg/kg in repeatable single-dose infusion injections. When administered as IV, it is converted into leucomethylene blue in the body, which decreases the heme group from methemoglobin to haemoglobin.

It has been proposed that this can contribute to the antiviral efficacy of this cheap and widely accessible dye-based medication against SARS-CoV-2, making it potentially beneficial in the prevention and treatment of COVID-19, particularly in underdeveloped and developing countries.

The most common symptom of the COVID-19 virus is fever and difficulty in breathing due to low oxygen levels. In septic shock and anaphylaxis, Methylene Blue is administered at a suggested dose of 1–2 mg/kg, resulting in a steady rise in blood pressure.

Drug Repurposing

 In the research paper by frontiersin.org published on Jan 13, 2021, Methylene Blue Inhibits the SARS-CoV-2 Spike–ACE2 Protein-Protein Interaction–a Mechanism that can Contribute to its Antiviral Activity Against COVID-19,

it was stated that after a series of experiments on the ability of Methylene Blue they were able to show Methylene Blue restricts the entrance of a pseudovirus containing the SARS-CoV-2 S spike protein into ACE2-expressing HEK293T cells. Because the pseudovirus expresses a bright green fluorescent protein that is targeted to the nucleus of ACE2 and red fluorescence reporter expressing host cells, this BacMam-based pseudovirus assay allows for the quantification of viral entry, and it can be handled using biosafety level 1 containment because it does not replicate in human cells. The presence of green fluorescence in the nucleus indicates the presence of a pseudovirus; if the entry is prevented, the cell nucleus stays black. Methylene Blue inhibited clearly in a concentration-dependent manner, with an estimated IC50 of 3.5 M.

Methylene Blue exhibited polypharmacology and worked on a wide range of targets; many of these, however, may have additional benefits in COVID-19 patients. Its major method of action is to reduce the oxidized ferric form of haemoglobin (Fe3+) to the ferrous (Fe2+) form when in a condition of methemoglobinemia, which binds oxygen irreversibly. This improved haemoglobin’s oxygen-binding capacity and, as a result, oxygen delivery to tissues–an essential advantage for COVID-19 patients. COVID-19 individuals frequently have low oxygen levels, which are generally incompatible with life without dyspnea–a condition known as silent hypoxemia.

Does Methylene Blue Actually Work?

Methylene Blue was reported to alleviate hypoxemia and hyperdynamic circulation in patients with liver cirrhosis and severe hepatopulmonary syndrome, which may be applicable here. In less-developed nations, MB is used to treat pneumonia and other respiratory diseases with moderate effectiveness.

Furthermore, Methylene Blue has been shown to block the PD-1–SHP2 PPI, which is downstream from the PD-1–PD-L1 co-signaling PPI, with low micromolar potency and effectively enough to counteract PD-1’s suppressive activity on cytotoxic T lymphocytes and restore their cytotoxicity, activation, proliferation, and cytokine-secreting activity. This exact mechanism targeting this co-signalling pathway (PD-1) may contribute to restoring T cell homeostasis and function from an exhausted state, which is important for improving viral clearance and reining in the inflammatory immune response and the related cytokine storm during anti-viral responses, such as those that cause the high mortality of COVID-19 patients.

In terms of therapeutic applications, a study on 2,500 French patients treated with Methylene Blue as part of their cancer treatment found that none of them had the influenza-like disease during the COVID-19 outbreaks. Methylene Blue was also studied in a Phase one clinical trial in Iran for the treatment of critically ill COVID-19 patients as part of a three-drug last therapeutic option add-on (MB 1 mg/kg, vitamin C 1500 mg/kg, and N-acetyl cysteine 2000 mg/kg) on the hypothesis that this integration could restructure NO, methemoglobin, and oxidative stress. Four out of five patients responded favourably to therapy.

Consequently, Methylene Blue was discovered as a low-micromolar inhibitor of the interaction between SARS-CoV-2 spike protein and its corresponding receptor ACE2, a PPI that is the first crucial step beginning the viral entry of this coronavirus. While Methylene Blue has a strong polypharmacology and maybe as PPI inhibitor, its ability to restrict this PPI may contribute to Methylene Blue antiviral activity against SARS-CoV-2 even in the absence of light, potentially making this inexpensive and widely available drug useful in the diagnosis and prevention of COVID-19 as an oral or aspirated medication.

Other articles on Methylene Blue:-

• Methylene Blue Dye | Chemistry, Uses & Side effects
• Methylene Blue Against Cyanide Poisoning
• Methylene Blue Injection: Indications, Dosage & Brands
• Staining with Methylene Blue
• Methylene Blue’s uses in Fish Aquaculture
• Methylene Blue in the treatment of Alzheimer’s
• Malaria Treatment with Methylene Blue
• Methylene Blue treatment for Lumpy Skin disease in cattle
• Methylene blue for treating Methemoglobinemia

Disclaimer-

The information provided here is based on general knowledge, articles, research publications etc and we do not claim the authenticity of any of the information provided above. We do not claim or suggest/advise any medical, therapeutic, health or nutritional benefits of MB. We do not supply or promote our MB product for the applications which are covered by valid patents and which are not approved by the FDA.

Macsen Labs is a manufacturer and supplier of several grades of Methylene Blue such as:-

• Methylene Blue USP
• Methylene Blue Zinc Free
• Methylene Blue BP 2000
• Methylene Blue BP 1973
• Methylthioninium Chloride BP
• Methylthioninium Chloride EP 9.0
• Methylthioninium Chloride E.P-10

Macsen Labs group’s Methylene Blue Synthesis Process granted a patent from the Indian patent office

The Indian Patent Office granted a patent to Mr Achal Agrawal, CEO of Macsen Labs, Udaipur. The title of the patent is Novel Improved Method for Synthesis of Diaminophenothiazine Compounds and it concerns a novel process for synthesising the compound Methylthioninium Chloride or Methylene Blue. Macsen Labs has now achieved a unique position by this patent and from now nobody will be able to copy this process. Read more