A newly characterized virus isolated from patients is an enveloped, positive-sense RNA virus that replicates entirely in the cytoplasm and encodes an RNA-dependent RNA polymerase (RdRp) not present in host cells. Which antiviral strategy is most rational and why?

• A. Design drugs that inhibit host mitochondrial DNA polymerase because mitochondrial dysfunction during viral infection will preferentially kill infected cells and therefore reduce viral spread with minimal systemic effects.
• B. Create antibody therapies targeting host cytokines to reduce inflammation, which will eliminate virus replication by removing all inflammatory mediators that the virus exploits for replication in the cytoplasm.
• C. Use DNA polymerase inhibitors because blocking host DNA synthesis will prevent cellular proliferation and thus indirectly stop viral replication in all infected tissues without needing to target any virus-specific enzyme.
• D. Develop nucleoside analogs targeting the viral RdRp to be incorporated into nascent viral RNA, because the RdRp is virus-specific and absent from host cells, maximizing selective toxicity.

Answer: (D)