#ChemVsCOVID series with the Royal Society of Chemistry examines how the Remdesivir drug is work. Remdesivir is a prodrug which is approved by the Food and Drug Administration (FDA) for the treatment of COVID-19 in hospitalized adult and pediatric patients. In November 2020,the US Food and Drug Administration approved Remdesivir which is first antiviral drug for COVID-19. While it's not as effective as was first thought, similar drugs look like they could be more successful. In the European Union, Remdesivir is indicated for the treatment of COVID 19 in adults and adolescents i.e. aged twelve years and older with body weight at least 40 kg with pneumonia requiring supplemental oxygen.
Remdesivir is a nucleoside analogue. We know that about, the Viruses need their RNA to copy to make more copies of themselves. In this process the enzyme is used called as RNA polymerase. RNA polymerase is a molecular copier that produces additional RNA strands. Nucleosides are the individual units in these strands.
Remdesivir comes as a solution and as powder to be mixed with liquid and infused into a vein over 30 to 120 minutes by a doctor or nurse in hospital. Remdesivir can be synthesized by in multiple steps from ribose derivatives. This drug is studied in several clinical trials. A patient with COVID-19 who receives a loading dose of Remdesivir 200mg would receive 6g to 12g of SBECD depending on the formulation.
Remdesivir structurally form looks very similar to adenosine. Adenosine is the nucleoside in RNA. There is two nitrogens in the top to right of molecule are identical to adenosine, so like adenosine they will form hydrogen bonds to Uridine, another RNA nucleoside. The difference between the Remdesivir and Adenosine is the Cyanide group added in Remdesivir. This affects the shape of the sugar part of the molecule, which in turn distorts the RNA polymerase can only add three more nucleosides before it comes crunching to a halt.
There are many common adverse effects in people treated with Remdesivir were respiratory failure and blood biomarkers of organ impairment including low albumin, low potassium, low count of red blood cells, low count of thrombocytes and elevated billirubin. Increase in levels of liver blood tests. Increase levels of liver enzymes have been seen in people who have received Remdesivir which may be a sign of inflammation or damage to cells in the liver.
Molnupiravir is also the nucleoside analogue being pursued as a COVID-19 treatment, looks more positive. Pharmaceutical major Merck and Ridgeback Biotherapeutics announced via a press release on October 1 the early results from Phase-3 trials that it's anti-viral drug molnupiravir halved the chances of hospitalisation in COVID 19 patients. After 1 month of monitoring, no deaths were reported in patients who received molnupiravir. Several noted clinicians have said that these are promising results, and what is particularly encouraging is that molnupiravir is a pill, unlike other drums with similar efficiency used in COVID 19 treatment which needs to be administered Intravenously.
The company name for molnupiravir is 'EIDD 2801' the 'E' indicating it was developed at Emory University. Antiviral drugs, and this includes the much in demand Remdesivir, work by inhibiting the process by which the virus replicates. Unlike Remdesivir, these structural changes don't directly stop the RNA copy being built. But because molnupiravir's active form can appear as two different nucleosides it confuses the RNA polymerase when it tries to recopy the copied RNA, introducing copying errors that lead to the virus demise.
A key challenge has been that many such antivirals, following a similar mechanism are not effective as oral pills. However, the Merck pill reportedly appears to have overcome this barrier and adds to it's promise as 'game-changing' pill amid the COVID-19 crisis.
Several countries have preemptively put in orders, though some safety concerns have been raised, and safety data has yet to be published, the drug passed phase 1 safety trials. Nucleoside analogues aren't the only COVID treatment drugs in development. These drugs bind to the viral protease enzyme and stop the virus from copying itself. Like vaccines, these antiviral medicines won't eradicate COVID. But they will hopefully help us reduce the numbers of hospitalisation and death from the disease. With many governments now pursuing a plan of "learning to live with the virus", this will be essential to reduce the numbers of preventable death.