Therapeutic p28 peptide targets essential H1N1 influenza virus proteins: insights from docking and molecular dynamics simulations

Graphic abstract The H1N1 influenza virus causes a severe disease that affects the human respiratory tract leading to millions of deaths every year. At present, certain vaccines and few drugs are used to control the virus during seasonal outbreaks. However, high mutation rates and genetic reassortment make it challenging to prevent and mitigate outbreaks, leading to pandemics. Thus, alternate therapies are required for its management and control. Here, we report that a bacterial protein, azurin, and its peptide derivatives p18 and p28 target critical proteins of the influenza virus in an effective manner. The molecular docking studies show that the p28 peptide could target C-PB1, NS1-ED, PB2-CBD, PB2-RBD, NP, and PA proteins. These complexes were further subjected to the simulation of molecular dynamics and binding free energy calculations. The data indicate that p28 has an unusually high affinity and forms stable complexes with the viral proteins C-PB1, PB2-CBD, PB2-RBD, and NP. We suggest that the azurin derivative p28 peptide can act as an anti-influenza agent as it can bind to multiple targets and neutralize the virus. Additional experimental studies need to be conducted to evaluate its safety and efficacy as an anti-H1N1 molecule.