A recent article published in the journal Science has shown that the already-promising drug candidate remdesivir, on trial now, exhibits promising activity against the COVID-19 causing virus and might work well in retarding virus replication.
The SARS-CoV-2 virus exists as a mere strand of RNA and it requires a host to replicate. Scientists have discovered that the active site of RDRp shows striking similarities with the Polio Virus and the Hepatitis C virus, and using that knowledge, they have tried to use known drug candidates that work in that RDRp environment and work back to see if they are effective with the novel coronavirus. They also showed exactly where on the RNA dependent RNA polymerase — the main machinery to form strands of RNA — that this drug will bind with. Remdesivir, a nucleotide analogue, then acts as part of the growing RNA chain, fooling the virus into believing it is replicating, and thereby stops true replication.
In the article “Structure of the RNA-dependent RNA polymerase (RDRp) from COVID-19 virus” Yan Gao et al, a group of researchers from various institutes in China and one in Australia, describes the biophysical and molecular interactions between COVID-19 virus RDRp and the antiviral drug remdesvir. “The findings highlight the fact that virus replication inhibitors hold promise and that the virus enzyme protein nsp12 represents a high value target to develop novel therapies for treating COVID-19 patients,” explains Panduranga Rao Varada, director, Animal Science Centre, Boston University.
Based on familiar viruses
“The RNA polymerase is what is used to replicate. Here, it began with the identification of similarities in viruses with which we are already familiar — Polio Virus and HCV. If the binding happens with the drug, virus proliferation can be reduced. Then, the stress on the immune system too will come down. This can reduce, to a large extent, the number of people slipping into a critical stage, having a positive impact on mortality and survival rates,” explains V. Dhanasekaran, a structural biologist, who also runs an education neuroscience start up.
The good news is that these candidates that seem to work well have already been tested, the safety and efficacy has been proven for other usage, Dr. Dhanasekaran adds. The study indicates sofosbuvir, along with remdesivir as probable candidates. Sofosbuvir is already being made in India to treat Hepatitis C, he adds.
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Currently, remdesivir, which is made by the American pharma company Gilead Sciences, is not available in India. With over 16 lakh cases of COVID-19 in 213 countries across the world, as per WHO statistics, and a record 99,690 confirmed deaths, the race to pick a winning candidate for treating and reducing the mortality and morbidity from the disease is on. A couple of trials, are already ongoing to test remdesivir, which has been already emerged as a promising candidate. This study further reinforces the viability of using the drug.