In silico identification of ivermectin as an influenza A virus nuclear export protein inhibitor

Abstract

Influenza A virus (IAV) is an etiological agent infecting animals and humans that is responsible for seasonal epidemics and devastating pandemics. IAV nuclear export protein (NEP) is a multifaceted protein that plays a pivotal role in the virus life cycle. One of the most important functions of IAV NEP is to transport newly synthesized viral ribonucleoproteins from the nucleus to the cytoplasm. This function is achieved by the interaction between NEP and matrix protein 1 (M1) facilitated by Trp78 surrounded by negatively charged Glu residues in the M1 binding domain of NEP. In the present study, we targeted the IAV NEP with ivermectin. Utilizing in silico molecular docking, we tested ivermectin for its ability to bind NEP. We found that ivermectin strongly binds to NEP with an affinity of –7.3 kcal/mol. The ivermectin binding site identified in this study is located in the NEP-M1 protein interaction region. It is anticipated that blocking NEP-M1 protein interaction can have a considerably deleterious effect on IAV assembly and propagation. This study highlights the possibility of exploring ivermectin as a potential IAV NEP protein blocker, which could be an important therapeutic strategy in the treatment of influenza.