RNA-dependent RNA polymerase inhibitors in COVID-19 therapy COVID19 coronavirus covid RNA
By Dr. Liji Thomas, MDOct 10 2022Reviewed by Danielle Ellis, B.Sc. The severe acute respiratory syndrome coronavirus 2 pathogen emerged in Wuhan at the end of 2019 to trigger the latest and most devastating coronavirus pandemic of the last hundred years. With a toll of six million deaths and counting, it triggered intense scientific efforts to discover effective and safe antivirals.
Emerging virus variants have displayed mutations in the spike protein that enhance virulence, transmissibility, or immune evasion capabilities. Therefore, antivirals remain a highly desirable goal, despite the rollout of numerous vaccines against the virus. All three types are activated by phosphorylation. This allows them to be inserted into the nascent RNA.
Molnupiravir is mutagenic in its antiviral action. However, since it may induce mutations in the host cell also, as observed in cell culture models, further study is required. Some in vitro evidence show cooperative inhibition of SARS-CoV-2 replication with a combination of these drugs. A small randomized clinical trial in moderate-severe COVID-19 patients supports their utility, with reduced hospital stays compared to standard COVID-19 care.
Their additional anti-inflammatory, antioxidant, immunomodulatory, and cardioprotective functions increase their potential usefulness in COVID-19. Other mechanisms are also being observed, such as electrostatic binding to RNA-binding proteins required for RNA replication and perhaps a synergistic effect with quinacrine on the SARS-CoV-2 main protease.
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