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

Outbreak of the SARS-CoV at Asia in 2013 was followed by the emergence of MERS-CoV in the Kingdom of Saudi Arabia 10 years later. Both virologists and epidemiologists predict that there will be more and more novel human coronaviruses emerging due to rapid mutation of viral genomes and the zoonotic features (54) (55) . Unfortunately, there is no approved vaccine for SARS or MERS. Therefore, the development of an antiviral strategy for rapid response to the emerging coronavirus infection is important. Antiviral approaches against viral −1 PRF have been targeting on the downstream stimulators (20) (21) (22) . Although small-molecule drugs provide uptake advantage, detailed structural information of the stimulator RNA is needed for this approach. Unfortunately, no high resolution −1 PRF stimulator structure of hCoV is available. Recently, three-dimensional RNA structure modeling of SARS-CoV −1 PRF stimulator pseudoknot in combination with computer-aided drug library modeling and screening have helped identifying potential leads for the inhibition of SARS-CoV −1 PRF (25) . However, the proposed binding pocket of the leads seems to be specific for SARS-CoV pseudoknot stimulator (25) .