Mechanisms of Coronavirus Genome Stability As Potential Targets for Antiviral Drugs

The COVID-19 pandemic has made it necessary to create antivirals active against the SARS-CoV-2 coronavirus. One of the widely used strategies to fight off viral infections is the use of modified nucleoside analogues that inhibit viral replication by incorporating DNA or RNA into the growing chain, thus stopping its synthesis. The difficulty of using this method of treatment in the case of SARS-CoV-2 is that coronaviruses have an effective mechanism for maintaining genome stability. Its central element is the nsp14 protein, which is characterized by exonuclease activity, due to which incorrectly included and noncanonical nucleotides are removed from the 3' end of the growing RNA chain. Inhibitors of nsp14 exonuclease and nucleoside analogues resistant to its action are viewed as potential targets for anticoronavirus therapy.