Parnad Basu, Amity University Kolkata
Remdesivir (C27H35N6O8P), is a broad-spectrum antiviral medication. It is administered via injection into a vein. Before the completion of clinical trials of the COVID-19 vaccines, remdesivir will be used to fight COVID-19. Now, COVID-19 is always mutating. And it is important to study those mutations to make remdesivir more effective against COVID-19. In a study done by scientists, it was found that SARS-CoV-2 needs a very less amount of mutation to grow remdesivir resistance.
Scientists obtained interacting residues between nsp12 and remdesivir from the cryoEM structure of the SARS-CoV-2 RdRp (RNA-dependent RNA polymerase). It was found that 56 residues obtained from nsp12 interacted with remdesivir. Out of those 56 residues 10 interacted with remdesivir and were essential to maintain the catalytic activity of RdRp. Scientists also sampled remdesivir-bound nsp12 by computing the total scores against the RMSD (root mean square deviation). This resulted in half of the top-scoring designs showing deviations in their RMSDs below 0.5 Å. Which made scientists believe that there was no significant deviation from the starting complex structure during repacking. In terms of binding affinity, affinity-attenuating designs showed significantly lower binding affinity.
In addition to that, it was concluded that some residues are prone to mutation and can form a resistance against remdesivir. Whenever the virus experiences evolutionary changes, the residues can show mutation finally resulting in remdesivir resistance.
However, predicting the evolution of a virus is certainly difficult. That too in case of a novel virus. Most SARS-CoV-2 genomes differ by few mutations, which enables the accurate investigation into spread patterns. Further studies on remdesivir resistance of SARS-CoV-2 genomes are to be done to find detailed information.
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Reference: High-Throughput Rational Design of the Remdesivir Binding Site in the RdRp of SARS-CoV-2: Implications for Potential Resistance Timir Tripathi et al.: https://doi.org/10.1016/j.isci.2020.101992
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