US, WASHINGTON (ORDO NEWS) — Researchers at the University of Alberta published an article in The Journal of Biological Chemistry claiming that the antiviral drug remdesivir effectively stops coronavirus replication. Previously, these same scientists reported that the drug works well against MERS-CoV, the causative agent of the Middle East respiratory syndrome.
Remdesivir is an antiviral drug of the class of inhibitors of RNA-dependent RNA polymerase (SARS-CoV-2 virus uses this type of polymerase). It was developed in 2015 by specialists from the US Army Infectious Diseases Research Institute. Remdesivir was actively used during the Ebola epidemic in 2018 and was found to be safe, although less effective than monoclonal antibodies.
A new article describes in detail the mechanisms of the drug. According to scientists, remdesivir cheats viruses by mimicking its building proteins. “These coronavirus polymerases are very careless and easily misleading,” said Mattias Goethe, one of the authors of the work, poetically describes coronavirus enzymes. “Therefore, the inhibitor is included [in the replication process] many times, and the virus is no longer able to multiply.”
Studies were performed on purified SARS-CoV-2 RNA polymerase. The enzyme actively included craftdivir (more precisely, its active triphosphate form), incorporating it into RNA instead of one of the nucleotides. This, in turn, led to the fact that, after three nucleotides from the built-in craftdeviir, RNA polymerase could not move further along the synthesized chain, and RNA synthesis was blocked.
A key feature of the craftsmanship is its high selectivity (biochemical selectivity). In this regard, it is more effective than triphosphate forms of antiviral drugs such as sofosbuvir, favipiravir and ribavirin.
According to the authors of the study, their results, supported by data from earlier studies on model animals and cell cultures, suggest that remdesivir can be classified as a “direct-acting antiviral agent”. This fact gives scientists confidence in the promise of clinical studies of remdesivir, which are now taking place in several countries, including Russia.
However, Matthias Goethe cautions that the positive results obtained in the laboratory cannot be used to predict results in humans. “We should be patient and wait for the completion of randomized clinical trials in humans,” he says.
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