A general strategy to inhibiting viral -1 frameshifting based on upstream attenuation duplex formation

Hu, Hao-Teng; Cho, Che-Pei; Lin, Ya-Hui; Chang, Kung-Yao

Mutagenesis in viral −1 PRF signals to change −1 PRF efficiency has been shown to impair the replication of several viruses, including HIV and severe acute respiratory syndrome coronavirus (SARS-CoV), suggesting that viral −1 PRF regulation is a potential antiviral means (20) (21) (22) . Given the crucial role of −1 PRF for efficient viral replication, different strategies have been developed to target viral −1 PRF stimulators to explore potential antiviral applications. Small ligands capable of interfering with viral −1 PRF activity by binding with the downstream −1 PRF stimulators of HIV and SARS-CoV have been identified either by screening or structure-based design (23) (24) (25) . Alternatively, antisense peptide nucleic acid (PNA) targeting the viral −1 PRF stimulator pseudoknot has been shown to impair the replication of an SARS-CoV replicon (26) . For both approaches, the functional characterization of a viral −1 PRF stimulator is required and this may represent a bottle-neck in combating emerging epidemic viral pathogens such as the MERS-CoV (27) .