Coronavirus RNA proofreading: molecular basis and therapeutic targeting

Official URL: https://dx.doi.org/10.1016/j.molcel.2020.07.027

The coronavirus disease 2019 (COVID-19) that is wreaking havoc on worldwide public health and economies has heightened awareness about the lack of effective antiviral treatments for human coronaviruses (CoVs). Many current antivirals, notably nucleoside analogs (NAs), exert their effect by incorporation into viral genomes and subsequent disruption of viral replication and fidelity. The development of anti-CoV drugs has long been hindered by the capacity of CoVs to proofread and remove mismatched nucleotides during genome replication and transcription. Here, we review the molecular basis of the CoV proofreading complex and evaluate its potential as a drug target. We also consider existing nucleoside analogs and novel genomic techniques as potential anti-CoV therapeutics that could be used individually or in combination to target the proofreading mechanism.© 2020 Elsevier Inc.Robson et al. examine the molecular basis of the coronavirus proofreading mechanism and how this contributes to the resistance of this family of viruses to nucleoside analog (NA) antiviral drugs. They discuss antisense oligonucleotide (ASO) therapy in combination with NAs to potentially improve the potency and delivery of antiviral drugs.