Besides the now approved remdesivir: Emerging options to treat Covid-19

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May 03, 2020 –  The world is desperate in the search for a treatment or better yet a vaccine in the Covid-19 pandemic. Slowly, there are some options emerging at least for the treatment of seriously ill Covid-19 patients. First of all,  the American Food and Drug Administration just issued an emergency use authorization (EUA) for the investigational antiviral drug remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. While there is limited information known about the safety and effectiveness of using remdesivir to treat people in the hospital with COVID-19, the investigational drug was shown in a clinical trial to shorten the time to recovery in some patients.

SARS-Cov-2 Interactome

Remdesivir is the first example of a candidate drug being repurposed towards treatment of Covid-19 disease from its original use in the treatment of the Ebola disease in the West African Ebola virus epidemic of 2013–2016 and also during the 2018  Kivu Ebola epidemic in the Democratic Republic of Congo.

Along these lines of repurposing drugs, early data on such efforts show that almost a dozen approved drugs could be effective against Covid-19 disease. Thus, according to a multidisciplinary study conducted by a large team of scientists in the United States and France that has just appeared in the Journal Nature, at least 10 different drug compounds ranging from cancer therapies to antipsychotics and antihistamines may be effective at preventing the SARS-CoV-2 from multiplying in the body.

The researchers mapped the human proteins SARS-CoV-2 interacts with inside the body when it infects cells and makes copies of itself, then looked for compounds that could block the virus from using those proteins, giving rise to a SARS-CoV-2 interactome. The result showed that 47 compounds in cell cultures had the desired effect, at least 10 of which are already in approved drugs or being studied for diverse conditions, but could be repurposed against COVID-19, the illness caused by SARS-CoV-2. In the study, candidates for repurposing included allergy medicine ingredients including clemastine, the antipsychotic haloperidol, and malaria drug hydroxychloroquine

Particularly the latter has stirred some controversy in the media and even among the clinical research community when it comes to a possible role of hydroxychloroquine as a treatment of Covid-19. Hydroxychloquine, sold, among others, under the brand name Plaquenil, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquineOther indications include rheumatoid arthritis, lupus, and porphyria cutanea tarda. In all these indications, side effects include vomiting, headache, changes in vision, and muscle weakness as well as more serious effects such as   allergic reactions, vision problems, and heart problems. Nevertheless, and despite some controversial study results about effectiveness and safety, hydroxychchloroquine remains one of the options of a repurposed drug for Covid-19 treatment.

By means of the SARS-CoV-2 interactome approach in the present study, a number of additional compounds have been identified with the potential of effectivity in the treatment of Covid-19. These include the experimental chemical, PB28, was 20-times more potent than hydroxychloroquine in targeting the cellular receptor for SARS-CoV-2, the hormone progesterone, and the antiviral plitidepsin, the pharmacologically active ingredient in Madrid-based PharmaMar’s experimental cancer therapy Aplidin. There are some interesting notions to these compounds. First, Plitidepsin is currently already being tested in Covid-19 trials in Spain. Secondly, Progesterone may help to explain some aspects of the fact that men seem more often affected than women and often show more serious disease progressions. And last but not least, the experimental chemical PB28 exhibited significantly less affinity than hydroxychloroquine for a heart protein which may be at the root for the known heart toxicity of hydroxychloroquine in some patients.

Some of the drugs and compounds tested in the researchers SARS-CoV-2 interactome approach have turned out, at least in the  laboratory setting, many times more potent than remdesivir. All these compound may be candidates for repurposing after thorough further in vitro and in vivo (i.e., clinical) development.

See here a sequence on how current drugs are being repurposed to possibly fight coronavirus (Covid-19):

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About the Author
Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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