Severe acute respiratory syndrome coronavirus 2 genomic and subgenomic RNA duplexes (SARS-CoV-2 gRNA/sgRNA duplexes)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic and subgenomic RNA duplexes are double-stranded RNA (dsRNA) structures that serve as essential intermediates in the viral life cycle (V'kovski et al., 2021, Nature Reviews Microbiology). Upon infection, the viral RNA-dependent RNA polymerase (RdRp) uses the positive-sense genomic RNA (gRNA) as a template to synthesize negative-sense RNA, forming a duplex that facilitates the production of new gRNA and a nested set of subgenomic RNAs (sgRNAs) (Kim et al., 2020, Cell). These sgRNAs are critical for the translation of structural and accessory proteins necessary for virion assembly. To protect these duplexes from host innate immune sensors like RIG-I and MDA5, the virus sequesters them within double-membrane vesicles (DMVs) derived from the endoplasmic reticulum (Wolff et al., 2020, Science). Because these dsRNA intermediates are unique to viral replication and absent in healthy human cells, they are high-priority targets for antiviral therapies. Current therapeutic approaches include small-molecule nucleoside analogs like Remdesivir and Molnupiravir, which disrupt the synthesis and fidelity of these duplexes, as well as emerging RNA-targeted platforms like siRNAs and antisense oligonucleotides designed to bind and degrade the viral RNA sequences directly.

Other names

SARS-CoV-2 double-stranded RNASARS-CoV-2 dsRNASARS-CoV-2 replication-transcription intermediatesSARS-CoV-2 gRNA/sgRNA

Inhibition of viral RNA-dependent RNA polymerase (RdRp) to prevent duplex formation and RNA interference (RNAi) to degrade existing viral RNA sequences.