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Those Nucleoside Analogues II — Remdesivir
By Nana Dadzie Ghansah
Around 2009, the company Gilead Sciences developed a whole slew of nucleoside analogues (NAs) for use as possible antivirals and anti-cancer drugs. One of these NAs was given the name GS-5734. It was analogous to the nucleotide adenosine. Shortly after it was made, it was found to inhibit the viral RNA polymerases of a host of viruses — Hepatitis C, Yellow and Dengue fevers, Influenza, the SARS-CoV, and RSV — in vitro and in mouse models. Later studies also showed it inhibiting MERS-CoV in-vitro and in mouse models.
During the 2013–16 Ebola outbreak in West Africa, investigators looked at whether GS-5374 could be used as treatment. In tests in monkeys, it was found to inhibit the viral RNA polymerase and thus stop viral replication. The outbreak was controlled before it could be used.
It found its clinical use for the first time in 2018 after Ebola broke out in the Congo. It was used in a trial as one of the treatments for the lethal infection. In the study known as the PALM trial, GS-5734 was compared to three other drugs, which were all monoclonal antibody preparations. It was found not to reduce mortality as well as the antibody preparations and was pulled from the trial. The development of an Ebola vaccine further reduced its usefulness as a drug one would need against the disease.
By this time, GS-5734 was known as “Remdesivir” and it looked like it was destined not to find any use as an antiviral. Then COVID-19 broke out.
In spite of the Ebola “failure”, GS-5734 is actually a very well-made nucleoside analogue. It has properties that make it a classic antiviral.
(Please refer to the image below for the sections of the compound being discussed. They are numbered from 1–5).
Though it is a nucleoside, it is made with one phosphate group. This means that once it enters the cell, it just needs only one phosphorylation step, thus foregoing the slow first phosphorylation step. Also, the phosphate group is bound to an…
