N-protein-RNA interaction is a drug target in a negative strand RNA virus

Chakraborty, Prasenjit; Chattopadhyay, Dhrubajyoti; Roy, Siddhartha

The negative strand RNA virus family contains many human pathogens. Finding new antiviral drug targets against this class of human pathogens is one of the significant healthcare needs. Nucleocapsid proteins of negative strand RNA viruses wrap the viral genomic RNA and play essential roles in gene transcription and genome replication. Chandipura virus, a member of the Rhabdoviridae family, has a negative strand RNA genome. In addition to wrapping the genomic RNA, its nucleocapsid protein interacts with the positive strand leader RNA and plays a vital role in the virus life-cycle. We have designed a peptide, based on prior knowledge and demonstrated that the peptide is capable of binding specifically to the positive strand leader RNA. When the peptide was transported inside the cell, it inhibited viral growth with IC(50) values in the low micromolar range. Given the widespread occurrence of leader RNAs in negative strand RNA viruses and its interaction with the nucleocapsid protein, it is likely that this interaction could be a valid drug target for other negative strand RNA viruses.