Computational screening of Traditional Chinese Medicine (TCM) library to identify potential inhibitors of H5N1 avian influenza neuraminidase: A molecular docking and dynamics simulation study

The influenza virus is a highly mutagenic pathogen that can drive a pandemic threat. This pandemic threat is currently very probable due to the recent outbreak of avian influenza H5N1 among cattle herds in United States. It is possible that this pathogenic strain can undergo evolution to easily infect other mammals including human beings. Therefore, it is of interest to identify new antiviral molecules that can fight both the circulating or novel strains of influenza. In this in-silico study, a library of Traditional Chinese Medicine (TCM) was screened against neuraminidase enzyme for H5N1 influenza virus. Both molecular docking and dynamics simulation were employed to identify potential inhibitors for N1 neuraminidase protein. According to the results of this study, both grosvenorine and pectolinarin are predicted to be effective N1 neuraminidase inhibitors. Evaluation of docking images points to the possibility that these two flavonoids may be engaged in multiple interactions with key residues in the active site of neuraminidase monomer. Additionally, the two compounds were able to record close proximity to target active site during simulation study. Also, the minimal average molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) binding energy was reported by pectolinarin throughout simulation interval. Finally, chemical and pharmacokinetics profiling refers to the possible hydrophilic nature of both grosvenorine and pectolinarin. Thus, these two compounds are expected to be soluble in water with low intestinal absorption. Also, both compounds are anticipated to be safe with high median lethal dose (LD50). However, these preliminary computation results must be further evaluated both in vitro and in vivo.