The recent coronavirus disease 2019 (COVID-19), causing a global pandemic with devastating effects on healthcare and social-economicsystems, has no special antiviral therapies available for human coronaviruses (CoVs). The severe acute respiratory syndrome coronavirus2 (SARS-Cov-2) possesses a non-structural protein (nsp14), with aminoterminal domain coding for a proofreading exoribonuclease (ExoN) that is required for high-fidelity replication. The ability of CoVs during genomereplication and transcription to proofread and exclude mismatched nucleotides has long hindered the development of anti-CoV drugs. The resistance of SARS-CoV-2 to antivirals, especially nucleoside analogs(NAs), shows the need to identify new CoV inhibition targets. Therefore, this review highlights the importance of nsp14-ExoN as a target for inhibition. Also, nucleoside analogs could be used in combination with existing anti-CoV therapeutics to target the proofreading mechanism.

Keywords: Coronavirus, Proofreading, Non-structural protein 14, Exoribonuclease, RNA recombination