## Positive-Sense RNA Genome as mRNA **Key Point:** SARS-CoV-2 is a positive-sense (+) RNA virus, meaning its genomic RNA is in the same polarity (sense) as mRNA and can function directly as mRNA for translation. **High-Yield:** The ~30 kb SARS-CoV-2 genome is 5' capped and 3' polyadenylated, mimicking eukaryotic mRNA structure. This allows immediate recognition by host ribosomes and translation of viral proteins without requiring transcription. ## Mechanism of Direct Translation ```mermaid flowchart TD A[SARS-CoV-2 enters cytoplasm]:::outcome --> B[Viral genome released]:::outcome B --> C{Genome polarity?}:::decision C -->|Positive-sense| D[Genome = mRNA]:::action D --> E[Ribosome recognizes 5' cap]:::action E --> F[Direct translation of ORF1ab polyprotein]:::action F --> G[Viral proteases cleave polyprotein]:::action G --> H[Functional viral enzymes produced]:::outcome ``` ## Structural Features Enabling Direct Translation | Feature | Function | | --- | --- | | 5' cap (7-methylguanosine) | Recognized by eIF4E; recruits ribosome | | 3' poly(A) tail | Enhances mRNA stability and translation efficiency | | Positive-sense polarity | Same as mRNA; directly translatable | | ORF1ab at 5' end | Encodes viral replicase complex (RdRp, protease, etc.) | **Clinical Pearl:** The first protein synthesized is the viral polyprotein (ORF1ab), which is then cleaved by viral proteases (3CLpro, PLpro) into functional enzymes. This is why protease inhibitors (e.g., nirmatrelvir in Paxlovid) are effective antivirals. **Mnemonic:** **CAPS** — Capped 5' end, Adenylated 3' tail, Positive-sense genome, Serves as mRNA directly.
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