Coronavirus genomic nsp14‐ExoN, structure, role, mechanism, and potential application as a drug target

Tahir, Mohammed

The recent coronavirus disease 2019 (COVID‐19), causing a global pandemic with devastating effects on healthcare and social‐economic systems, has no special antiviral therapies available for human coronaviruses (CoVs). The severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2) possesses a nonstructural protein (nsp14), with amino‐terminal domain coding for proofreading exoribonuclease (ExoN) that is required for high‐fidelity replication. The ability of CoVs during genome replication 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.