Investigating -1 PRF in Coronaviruses
Overview. Coronaviruses are positive-strand RNA viruses that represent a significant threat to public health because they have pandemic potential. Antiviral therapies that stop viral replication are key to limiting viral transmission and disease. Steps in the viral life cycle that are both unique to the virus and critical to viral replication represent good antiviral targets. During an early step in the coronavirus life cycle, the RNA genome is translated to produce viral polyproteins. A subset of these proteins, including the RNA dependent RNA polymerase (RdRp), are synthesized by way of a -1 PRF (Figure 5A). This translational event is critical to the coronavirus life cycle because this is how the main replicative enzyme for the virus, the RdRp, is synthesized. Previous research on the SARS coronavirus revealed that altering its -1 PRF efficiency drastically reduced viral replication, suggesting this step is a viable antiviral target. Given that coronavirus frameshift sites are highly-conserved in both sequence and structure, antiviral treatments that target frameshift sites are not likely to readily select for viable drug-resistant virus isolates. Research on -1 PRF in coronaviruses will be important to future drug development efforts targeting this step in the viral life cycle.
Relevant publications: we just started this research in June, 2020, and thus, don’t have any publications to share just yet.
