Severe acute respiratory syndrome coronavirus 2 genomic and subgenomic RNA (SARS-CoV-2 RNA)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic RNA (gRNA) is a single-stranded, positive-sense RNA molecule of approximately 30 kilobases that serves as the primary genetic blueprint for the virus [1]. Upon entering a host cell, the gRNA is translated to produce non-structural proteins that form the replication-transcription complex, which then synthesizes a series of nested subgenomic RNAs (sgRNAs) [2]. These sgRNAs are essential for the translation of structural proteins, such as Spike (S), Envelope (E), Membrane (M), and Nucleocapsid (N), as well as various accessory proteins required for viral pathogenesis and immune evasion [1,3]. As a therapeutic target, the RNA can be directly addressed using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) that trigger degradation or block translation, as well as small molecules that target highly conserved secondary structures like the 5' untranslated region (UTR) or the ribosomal frameshifting element [4]. Drugs like Molnupiravir act by being incorporated into the nascent RNA strand, leading to an accumulation of mutations that render the virus non-functional, a process known as lethal mutagenesis [5]. Targeting the RNA genome is a robust strategy because it can focus on highly conserved regions that are less prone to the mutations seen in surface proteins like the Spike protein [4]. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205740/ [2] https://www.nature.com/articles/s41586-020-2277-z [3] https://www.cell.com/cell/fulltext/S0092-8674(20)30462-3 [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415559/ [5] https://www.nature.com/articles/s41586-021-03544-w

Other names

SARS-CoV-2 gRNASARS-CoV-2 sgRNASARS-CoV-2 transcriptomeSevere acute respiratory syndrome coronavirus 2 genome2019-nCoV RNA

Inhibition of viral replication through chain termination, induction of lethal mutagenesis (error catastrophe), RNA interference (RNAi) mediated degradation, or antisense-mediated steric hindrance of translation and replication.