The effects of mutation on the drug binding affinity of Neuraminidase: case study of Capsaicin using steered molecular dynamics simulation.

The influenza virus is an important respiratory pathogen that causes many incidences of diseases and even death each year. One of the primary factors of this virus is the Neuraminidase surface protein, which causes the virus to leave the host cell and spread to new target cells. The main antiviral medication for influenza is designed as a protein inhibitor ligand that prevents further spread of the disease, and eventually relieves the emerged symptoms. The effectiveness of such inhibitory drugs is highly associated with their binding affinity. In this paper, the binding affinity of an herbal ligand of Capsaicin bound to Neuraminidase of the influenza virus is investigated using steered molecular dynamics (SMD) simulation. Since mutations of the virus directly impact the binding affinity of the inhibitory drugs, different mutations were generated by using Mutagenesis module. The rapid spread of infection during the avian influenza A/H5N1 epidemic has raised concerns about far more dangerous consequences if the virus becomes resistant to current drugs. Currently, oseltamivir (Tamiflu), zanamivir (Relenza), pramivir (Rapivab), and laninamivir (Inavir) are increasingly used to treat the flu. However, with the rapid evolution of the virus, some drug-resistant strains are emerging. Therefore, it is very important to seek alternative therapies and identify the roots of drug resistance. Obtained results demonstrated a reduced binding affinity for the applied mutations. This reduction in binding affinity will cause the virus mutation to become resistant to the drug, which will spread the disease and make it more difficult to treat. From a molecular prospect, this decrease in binding affinity is due to the loss of a number of effective bonds between the ligand and the receptor, which occurs with mutations of the wild-type (WT) species. The results of the present study can be used in the rational design of novel drugs that are compatible with specific mutations.