Structural analysis of viral ExoN domains reveals polyphyletic hijacking events

Nidoviruses and arenaviruses are the only known RNA viruses encoding a 3’-5’ exonuclease domain (ExoN). The proofreading activity of ExoN has played key role in growth nidoviral genomes, while this partakes suppression host innate immune signaling. Sequence structural homology analyses suggest that these proteins have been hijacked from cellular hosts many times. Analysis available sequences reveals high conservation level comparable to viral RNA-dependent polymerases (RdRp), which most conserved proteins. Two highly preserved zinc fingers present all exonucleases, arenaviral protein one finger can be identified. This is sharp contrast with reported lack ExoNs, opens possibility therapeutic strategies struggle against COVID-19.