SARS-CoV-2

Inhibition of SARS-Cov-2 programmed ribosomal frameshifting

Project is FOUNDED BY THE POLISH NATIONAL SCIENCE CENTRE (NCN)
SARS-CoV-2, a causative agent of COVID-19 pandemic, is a positive-sense single-stranded RNA virus, closely related to the SARS-CoV-1 responsible for the SARS epidemic. A key mechanism required for translation of coronavirus genome is -1 programmed ribosomal frameshifting (-1PRF). A defined proportion of ribosomes translating orf1a switches the reading frame at the precise location and decodes orf1b. This event is essential for the synthesis of viral RNA-dependent RNA Polymerase and thus replication and propagation of the virus. The ratio of ribosomes, which undergo frameshifting is tightly regulated and any deviation from the programmed value impacts virus proliferation capability. 
 
We study the mechanisms driving the ribosomal frameshifting in SARS-CoV-2, with the focus on translation initiation. We are interested in prospects of designing small molecule-based inhibitors of the frameshifting process.