In silico analysis of Moroccan medicinal plant compounds as potential inhibitors of influenza A (H3N2)

The treatment of influenza A, particularly the H3N2 subtype, remains a major challenge due to the seasonal mutations of this virus. These mutations complicate the development of effective treatments. Influenza A, specifically the H3N2 strain, is responsible for severe respiratory infections, which impact public health and contribute to global epidemics.

This study aims to explore the antiviral inhibitory potential of compounds derived from Moroccan medicinal plants, sourced from different regions, targeting the biologically active sites of the H3N2 virus. Two types of viral proteins, hemagglutinin (HA) and nucleoprotein (NP) of the H3N2 influenza virus, representing distinct functional mechanisms (PDB ID: 4we8 for HA and PDB ID: 7nt8 for (NP), were selected for this investigation. In silico studies, such as molecular docking, ADMET(Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties evaluation, and molecular dynamics simulation, were employed to predict the interactions and energy scores of candidate molecules with the two proteins, evaluate the bioavailability and behavior of these molecules within the human body, and assess the stability of the selected candidates with the two proteins. The ultimate goal is to identify potential inhibitors that could be developed into drugs. Several molecules were selected through molecular docking and ADMET evaluation, and their further study through molecular dynamics simulation aims to propose promising anti-H3N2 inhibitors. Indeed, compound no. 329, which multitargets both HA and NP structures, was chosen as it met all the criteria for eventual in vitro and in vivo validation.