Small-molecule inhibitors targeting the catalytic site and allosteric pockets of Mononegavirales RNA polymerases reveal conserved druggable pockets for broad-spectrum antiviral development.
Structural and biochemical insights into Mononegavirales polymerases reveal conserved druggable pockets that could guide the development of broad-spectrum antivirals.
ABSTRACT The order Mononegavirale s includes several non‐segmented negative‐sense RNA viruses that are significant human pathogens, whose transcription and replication depend on multifunctional RNA‐dependent RNA polymerase (L protein). Recent discoveries in cryo‐electron microscopy (cryo‐EM) have elucidated the structures of these polymerases and their interactions with small‐molecule inhibitors, providing possible insights for antiviral design. This review summarizes current developments and discoveries in small‐molecule inhibition of Mononegavirales polymerases, exploring nucleoside/nucleotide inhibitors that target the catalytic site and non‐nucleoside inhibitors that engage allosteric pockets within the L protein. By combining biochemical and structural findings, these studies reveal conserved druggable pockets, providing opportunities for the development of broad‐spectrum antivirals drugs against Mononegavirales pathogens.
Cao et al. (Fri,) conducted a review in Mononegavirales infections. Small-molecule inhibitors was evaluated. Small-molecule inhibitors targeting the catalytic site and allosteric pockets of Mononegavirales RNA polymerases reveal conserved druggable pockets for broad-spectrum antiviral development.