Can Hydroxychloroquine be Used to Treat Coronavirus?
This drug has received fanfare for its treatment for lupus and is best known as an anti-malarial medication.
The mechanism of action of hydroxychloroquine in both diseases is the inhibition of intracellular processes that are pH-dependent. In patients with malaria, it prevents degradation of hemoglobin (the oxygen carrying component of blood), while for lupus patients it prevents T-cell activation.
Hydroxychloroquine also plays a role in inhibiting the movement of some types of white blood cells, and this inhibition can help decrease inflammation.
In regards to treatment against the coronavirus, this therapy was first proposed in November 2003 in an article entitled “Effects of chloroquine on viral infections: an old drug against today’s diseases,” where the authors demonstrated how the medication can be used against flaviviruses (e.g. Dengue, Zika, West Nile), retroviruses (e.g. HIV), and coronaviruses (e.g. SARS-CoV [the first SARS virus]). And it has since been demonstrated that it can have effects over an even greater spectrum of viruses.
Hydroxychloroquine works in a similar way against some of these viruses, namely HIV though possibly SARS-CoV-2, as it does against malaria and lupus. It works against pH-dependent processes utilized by these viruses, preventing normal processing of the virus inside of the cell’s Golgi apparatus, creating non-infectious particles.
The particles are non-infectious because the viral proteins are not properly modified, so the virus is not able to ever leave the infected cell. The cell may then recognize the foreign viral material and send out a distress signal which will lead to its death.
Another way hydroxychloroquine has such a great effect on so many viruses is through inhibition of sialic acid, which some viruses use to attach to a cell surface prior to entry. It is still being researched to see if SARS-CoV-2 uses this for entry.
However, it is known that both SARS-CoV-1 and 2 use the same surface receptor called ACE2, and hydroxychloroquine affects that receptor in a way that prevents infection. It seems that against the coronaviruses, hydroxychloroquine inhibits fusion of the viral and endosomal membranes due to raising the pH.
Hydroxychloroquine is a base, and hogs protons for itself, disallowing membrane fusion and thus preventing the viral nucleic acid from ever entering the cell where it would utilize host machinery to make more viral particles.
Hydroxychloroquine also has an anti-inflammatory role, inhibiting the production of three important mediators of inflammation: tumor necrosis factor alpha, interleukin 1, and interleukin 6. Every time you’ve ever had a fever, these three are the culprits. These are also responsible for kickstarting the inflammatory process that will end in vasodilation and increased vascular permeability to allow white blood cells to travel to the site of infection and enter into the tissue.
Neutrophils are a type of white blood cell that enters into the tissue and releases all sorts of mediators that cause injury—to both the pathogen and our own cells.
Any zit you’ve ever had in your life that had pus inside of it is essentially dead neutrophils that have blown themselves up in an effort to fight off infection. With tissue injury comes the rebuilding process and if your body overdoes that rebuilding process you can end up with long-term fibrosis (which can be a long-term result in those who have survived SARS-1 or SARS-2.). Since hydroxychloroquine can block this process, this is another way it can be used to treat autoimmune disorders such as lupus.
Hydroxychloroquine is especially important in its role in preventing a “cytokine storm,” which is when there are so many immune mediators being released at once to fight an infection that the host itself is overwhelmed and dies. Cytokine storms have been implicated in the death of SARS patients.
The most serious side effects of hydroxychloroquine are retinopathy, occurring in roughly 4% of patients treated for five or more years, other associated ophthalmic pathologies that may be reversible, and rare cases of cardiomyopathy. Since antiviral therapy would be relatively short-term, these side effects would be rare. The rest of the side effects do not have a defined frequency and are the standard side effects one expects to see for any medication.
Prescribing hydroxychloroquine as first-line therapy for SARS patients might be our best option currently.
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