INTERACTION MECHANISMS OF NOVEL ANTIVIRAL PEPTIDES AGAINST N1 SUBTYPE NEURAMINIDASE: A COMPUTATIONAL EXPLORATION

In light of the current pandemic threat and the emergence of drug resistances, the development of next-generation anti-influenza agents must be a high priority, with many efforts to bind with the 150-cavity of N1 subtype neuraminidase (NA). In this work, docking and explicit solvent molecular dynamics simulations were combined to study the interactions between N1 subtype NA and novel inhibitory peptides EISYIHAEAYRRGELK, YIHAEAYRRG and HAEAYR. It was found that 16-mer peptide EISYIHAEAYRRGELK has the binding specificity to N1 subtype NA and the capability to lock the 150-cavity. The binding-site residues Asp198, Glu227 and Glu229 play important roles during the binding process. Compared with the 16-mer peptide, YIHAEAYRRG and HAEAYR even tightly coordinated to the 150-cavity, especially of the latter. The total interaction energies (E-total) of them with N1 subtype NA were calculated to be -578.21, -442.21 and -358.80 kcal mol(-1), respectively. Further energetic and geometric analyses revealed that the portion of Tyr-Arg in peptides is more helpful for maintaining favorable contacts with residues around 150-cavity and is of great importance in the scaffold modification. We hope that the results will be helpful for designing novel anti-influenza drugs.