Experimental antiviral drug brings hope for coronavirus treatment

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The experimental antiviral drug remdesivir is currently perhaps the best hope for the treatment of SARS-CoV-2 coronavirus. Clinical trials currently underway in the US and China are expected to yield results in April.

Remdesivir is a broad-spectrum experimental antiviral drug, but to date it has not been licensed anywhere in the world for any use. It was originally studied to treat Ebola virus. Although its effectiveness in the case of Ebola has not proved to be good, those studies have shown its safety for human use.

It has demonstrated activity both in vitro and in vivo in experimental animals against the MERS-CoV and SARS-CoV viruses, which are also coronaviruses and are structurally similar to SARS-CoV-2. This experimental drug has so far been used in a small number of new coronavirus infections and therefore more extensive studies are needed to determine its efficacy.

One rational approach to the rapid discovery of a drug against the new coronavirus is to control the activity that existing antiviral drugs may present. Towards this end, efforts began in China where researchers at the Wuhan Institute of Virology investigated the in vitro antiviral efficacy of five FDA-approved drugs (ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine) and two well-known anti-viral drugs. medicines of remdesivir and favipiravir. Remdesivir and chloroquine clearly showed the best in vitro results indicating the need for further studies.

Two Phase 3 clinical trials have been launched in March to evaluate the safety and efficacy of remdesivir. following approval by the FDA of Gilead’s request that this drug be developed. These studies are randomized, open-label multicenter studies that will include 1000 patients in medical centers of mainly Asian countries, but also of other countries around the world where there are a large number of cases. The first will evaluate the safety and efficacy of remdesivir after five or ten days of treatment in patients in severe condition, and the second in patients with moderate to severe disease.

China’s health authorities have also launched two clinical trials for the evaluation of safety and efficacy of remdesivir mainly in Hubei province where Wuhan belongs. These studies began in February.

In parallel, Gilead in collaboration with governmental and non-governmental organizations and authorities provides remdesivir for emergency use in the absence of approved treatment (compassionate use). ‘Remdesivir will also be used in Greece in this context initially.

Remdesivir is a small nucleotide-like molecule that is a prodrug (its chemical formula is shown in the following figure). It should be noted that a large number of nucleotide analogs have been designed and synthesized in the past to treat novel viruses. ‘A successful example of a nucleoside analogue is AZT, the first drug developed against AIDS.

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The study of other drugs already approved for the treatment of the new coronavirus has the great advantage of being able to use the drug immediately if its efficacy against SARS-CoV-2 is confirmed.

* The text is signed by Mr George Kokotos
Professor of Organic Chemistry-Pharmacochemistry, NCSR
Center of Excellence for the Design and Discovery of Medicinal Products of NCSR

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