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Cap-dependent endonuclease (CEN) is a viral enzyme critical for the replication and transcription of certain negative-strand RNA viruses, most notably influenza viruses. It is a component of the viral RNA polymerase complex and plays an essential role in the "cap-snatching" mechanism, which allows the virus to hijack host mRNA caps to prime synthesis of its own mRNAs. Inhibitors targeting CEN have shown broad-spectrum antiviral potential against various influenza strains due to high conservation among different types/subtypes. Resistance mutations can arise but typically involve changes at or near key residues coordinating metal ions or substrate recognition within PA’s N-terminal region.
Inhibition of cap-dependent endonuclease activity by binding to the active site and preventing host mRNA cleavage and primer generation for viral mRNA synthesis.
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