Saturday, May 2, 2020

The Mode of Action of the Anti-viral Drug Remdesivir

Currently, the United States along with many parts of the world is being severely impacted by the COVID-19 pandemic. As discussed in more detail in previous reports, COVID-19 is an RNA virus that was previously resident in another mammalian species and underwent a genetic modification that allowed it to cross species to humans – a not uncommon event among viral pathogens. The current genetic evidence is strongly suggestive that the mammalian species from where the virus originated was the bat. 

Recent clinical trials have demonstrated that the anti-viral drug remdesivir has some efficacy in the treatment of the illness brought about by COVID-19 infection. Remdesivir is a nucleoside analog (structure shown below)

Structure of Remdesivir

Inside the target host cell – lung tissue as an example – this substance functions as an inhibitor of the process that is involved in viral replication. The drug’s specific target tin RdRp (see diagram below) – the protein complex that the coronavirus uses to replicate its RNA genome.

Structure of RdRp

According to a report presented by E.S. Amirian, “After the host metabolizes remdesivir into active nucleoside triphosphate (NTP), the metabolite competes with adenosine triphosphate (ATP; the natural nucleotide normally used in this process) for incorporation into the nascent RNA strand – effectively substituting the drug metabolite for ATP. The incorporation of this substitute into the new strand results in premature termination of RNA synthesis, halting the growth of the RNA strand after a few more nucleotides are added. Although coronaviruses (CoVs) have a proofreading process that is able to detect and remove other nucleoside analogs, rendering them resistant to many of these drugs, remdesivir seems to outpace this viral proofreading activity, thus maintaining antiviral activity. Unsurprisingly, Agostini et al. reported that a mutant murine hepatitis virus (MHV) devoid of proofreading ability was more sensitive to remdesivir.”

Since viruses are prone to mutations, it is also possible that that mutations could spontaneously occur that would effectively improve proofreading and result in remdesivir resistance. In addition, it also quite possible that the effectiveness of this anti-viral drug could be due to additional factors that are currently unknown.

At the present time, in-vitro and clinical trials have yielded strong suggestive evidence that remdesivir may provide a clinical route to a therapy that could be applied to COVID-19 patients. Ongoing studies are also investigating the possibility of finding additional drugs that could provide a synergistic effect to further improve positive outcomes.

This line of investigation together with a fast-track search for an effective vaccine may ultimately safe countless lives worldwide. These scientific investigations highlight the intrinsic and inestimable value that the ongoing scientific studies contribute to humanity and its future.

No comments:

Post a Comment