Research Projects

The COVID-19 outbreak has led to the search for new therapeutic targets, such as targeting the viral genome. The SARS-CoV2 virus's RNA genome contains programmed -1 ribosomal frameshifting (-1 PRF) elements, which are essential for replicating its genome and transcription of viral genes. This has led to the development of RNA binding agents that inhibit -1 PRF, which are less prone to drug resistance. The current proposal aims to identify a SARS-CoV2 pseudoknot binding agent that inhibits -1 programmed ribosomal frameshifting. The RNA binding affinity of hits will be validated using SPR studies. The method involves screening a focused RNA library using a dual luciferase assay, further screening for antiviral assay, and resynthesizing and validating active ligands for antiframeshifting and antiviral activity. The binding affinity of HITS to RNA will be confirmed using SPR studies. The proposed study aims to identify a new class of antiframeshifting agents with proven RNA affinity and antiframeshifting capability at the molecular level. The identified agents will be patented and taken up for hit-to-lead optimization in the future, potentially acting as broad-spectrum antivirals in future viral outbreaks. The identified agents will be taken up for hit-to-lead optimization in the future.