Drugging SARS-CoV2 RNA-protein interactions
Coronaviruses are single strand RNA viruses responsible for respiratory tract diseases including the current global pandemic. An RNA-protein interaction is critical for successful coronavirus replication. The SARS-CoV2 RNA genome is packaged into the virus nucleocapsid by the N protein, an RNA binding protein (chaperone) shown schematically above. Inhibiting the N protein interaction with the viral genome packaging sequence is expected to lead to virus capsids lacking RNA genomes, which are non-infectious particles. We have used our RNA discovery platform to identify the minimal RNA genome packaging sequences binding to the N protein. In addition to identifying disease-causing RNA-protein interactions, our platform can be used to discover small molecules that inhibit these disease-causing RNA-protein interactions. That is, we are “drugging” the interaction rather than either of the components alone. This work is one example of industry-sponsored research (Takeda) primed to generate data that allows translation to the clinic in the future.
In addition to finding inhibitors of viral RNA-protein interactions, we are planning to inhibit interactions between viral RNAs and cellular proteins that block virus replication.
There are known human protein interactions with viral RNAs that can affect coronoa virus replication. For example the human polypyrimidine tract binding (PTB) protein (aka. hnRNP I) has been shown to interact with pentanucleotide repeats in the 5’ UTR of the viral genome. Moreover,
We are looking to identify other viral RNA-human protein interaction and inhibitors of this interactions to inhibit viral replication.
Mouse models to study the effect of this protein-RNA interactions and their inhibition of coronavirus replication.
In addition to finding inhibitors of viral RNA-protein interactions, we are planning to inhibit interactions between viral RNAs and cellular proteins that block virus replication.
There are known human protein interactions with viral RNAs that can affect coronoa virus replication. For example the human polypyrimidine tract binding (PTB) protein (aka. hnRNP I) has been shown to interact with pentanucleotide repeats in the 5’ UTR of the viral genome. Moreover,
We are looking to identify other viral RNA-human protein interaction and inhibitors of this interactions to inhibit viral replication.
Mouse models to study the effect of this protein-RNA interactions and their inhibition of coronavirus replication.
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