Surface charm

April 2, 2020

A small pilot study from France showed that all six COVID-19 patients given a hydroxychloroquine/azithromycin combination recovered quickly from the disease, despite initial disease severity requiring hospitalization.  In addition, these drugs were shown to inhibit SARS-CoV-2 virus infection in a dish in the laboratory (in vitro). This vertical consistency in efficacy from the clinic to the lab, along with the established safety profile of these drugs, led to a strong effort to advance these drugs as repurposed for treating COVID-19 disease. 

Hydroxychloroquine and its parent drug chloroquine are ancient malaria drugs that have since found a use in controlling autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. Despite their long-time and broad clinical use, the mechanism of action of these drugs remains unknown, although many intriguing observations have been made. Importantly, these drugs have ideal pharmacokinetic properties and their safety profiles are well understood.  In terms of the former, they distribute well throughout the body and are not metabolized too quickly to have their effect. Interestingly, they bind to the skin pigment melanin, so they accumulate and may have higher activity at body surfaces, like skin or mucous membranes, which may be part of the secret to their success. (Tissue-specific activity is our mantra here at GeneCentrix). Their toxicity is largely from chronic use, so they are ideal for short term use in COVID-19, if they have true efficacy.

 

Although they are both indicated for infectious disease (azithromycin is an antibiotic), both are well known to be immunomodulatory and/or anti-inflammatory. This begs the question as to whether the immune response to the virus is more dangerous than the viral infection itself: Perhaps these drugs improve the clinical course by affecting the former without affecting the course of the viral infection. Physicians are loathe to introduce immune suppressors during an infection for obvious reasons, but some of the immune modulating drugs are specific to inflammation and immune responses that are not directly anti-viral.  Hydroxychloroquine and azithromycin may be two of these. Fortunately, the constellation of possibilities with these drugs is sufficiently intriguing that many clinical tests, including off-lable use, have been initiated. We will find out soon one way or another whether these drugs work.

 

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