While the debate about ivermectin and hydroxychloroquine rage on, doctors are beginning to discover the benefits of methylene blue for treating COVID-19.
Research shows that the oxygen carrying capacity of red blood cells increases when a patient receives a methylene blue treatment. In addition, a recent study shows that methylene blue acts as a low-micromolar inhibitor of the SARS-CoV-2 spike protein and ACE2 interaction.
The severe acute respiratory syndrome coronavirus (SARS-CoV-2), causes the continuing outbreaks of COVID-19. Worldwide, healthcare systems and entire economies have been greatly impacted. While COVID-19 vaccines have been introduced at lightning speed, the virus has gone through multiple genomic variations resulting in new strains. The data on the vaccines and adverse reactions are generating questions into their efficacy, which is a key reason that researchers and doctors continue to seek new therapeutics in the fight against COVID-19.
Oral antivirals to treat COVID-19
Many scientists suggest that COVID-19 may need an orally bioavailable antiviral for effective treatment. Thus, the United States Food and Drug Administration (FDA) has given emergency use authorization to 2 new drugs, nirmatrelvir (suppresses virus reproduction) and molnupiravir (inhibits protease activity). In addition, scientists have investigated small molecule inhibitors (SMIs) of protein-protein interactions (PPIs) as a potential treatment for COVID-19.
With this in mind, researchers are looking at potential inhibitors of the PPIs between the spike protein and cell surface receptors. Such an inhibitor could prevent the cell attachment and entry of the virus into the cell. However, finding an SMI for this task has been challenging, although researchers have made progress. The FDA has given approval for clinical use to 3 SMIs: fostemsavir, lifitegrast, and venetoclax.
Methylene blue to treat COVID-19
A new study published in the preprint server, bioRxiv, looked at identifying potential SMIs of the PPI for COVID-19. The same research team had previously conducted a different study that bound methylene blue was effective in treating acquired methemoglobinemia. They reported that methylene blue can effectively inhibit the SARS‐CoV‐2–ACE2 PPI and the entry of SARS‐CoV‐2‐spike‐bearing pseudo virus into the ACE2 expressing cells.
The new study found the methylene blue also worked against variants of the SARS-CoV-2 virus including the Delta and D614G strains.
Methylene blue suppresses key interactions
The current study showed that methylene blue suppresses the interaction between SARS‐CoV‐2 spike protein and hACE2. In addition, the scientists found that methylene blue can inhibit the SARS-CoV-2 Delta strain, which appears to be more virulent than other strains. The study showed the potential for the compound to be a cost-effective antiviral treatment for a SARS-CoV-2 infection.
Light therapy combined with methylene blue
Earlier studies found that methylene blue in combination with light therapy acts as a broad spectrum virucidal. This has been used since 1991 to kill viruses in blood products prior to a transfusion. Recent studies show that methylene blue is effective against both the influenza virus and SARS-CoV-2 virus, even at low concentrations and without in combination with light therapy.
These studies suggested that the antiviral properties of methylene blue may be due to several mechanisms of action. One of these mechanisms is enhanced genomic RNA degradation when used with light therapy. The duration of light exposure also influences the extent of genomic RNA degradation.
The research team determined that the concentration of Methylene blue is 5.0 mM for clinical antiviral use. This is within the range of oral administration. The half-life elimination and the oral bioavailability also fall within the range for oral doses.
Methylene blue is considered safe, although it can have side effects at inappropriate doses including nausea, vomiting, hemolysis, and other undesired side effects. In addition, people taking SSRIs for depression may find that methylene blue negatively impacts the serotonin reuptake inhibitor.
Currently, researchers are conducting trials in Switzerland, Mexico, and Iran to determine the effectiveness of methylene blue to treat COVID-19. A preliminary report suggests that oral doses can reduce hospital stays and reduce mortality rates.
In addition, researchers found significant efficacy with no side effects in intravenous methylene blue (1 mg/kg) treatment used as rescue therapy for moderate to severe hypoxic COVID‐19 patients with acute respiratory distress syndrome (ARDS). Researchers observed that nebulized methylene blue treatment in patients with COVID‐19 infections showed remarkable benefits, including a decrease in inflammatory markers and oxygen requirements.
Final thoughts
This is exciting news about methylene blue, which is proving to be a safe, effective treatment for many illnesses. Adding this compound to the arsenal of treatments against SARS-CoV-2 is a welcome development. We expect future studies to find similar results.