title: Identification of novel compounds against an R294K substitution of influenza A (H7N9) virus using ensemble based drug virtual screening.
abstract: Influenza virus H7N9 foremost emerged in China in 2013 and killed hundreds of people in Asia since they possessed all mutations that enable them to resist to all existing influenza drugs, resulting in high mortality to human. In the effort to identify novel inhibitors combat resistant strains of influenza virus H7N9; we performed virtual screening targeting the Neuraminidase (NA) protein against natural compounds of traditional Chinese medicine database (TCM) and ZINC natural products. Compounds expressed high binding affinity to the target protein was then evaluated for molecular properties to determine drug-like molecules. 4 compounds showed their binding energy less than -11 Kcal/mol were selected for molecular dynamics (MD) simulation to capture intermolecular interactions of ligand-protein complexes. The molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method was utilized to estimate binding free energy of the complex. In term of stability, NA-7181 (IUPAC namely {9-Hydroxy-10-[3-(trifluoromrthyl) cyclohexyl]-4.8-diazatricyclo [6.4.0.02,6]dodec-4-yl}(perhydro-1H-inden-5-yl)formaldehyde) achieved stable conformation after 20 ns and 27 ns for ligand and protein root mean square deviation, respectively. In term of binding free energy, 7181 gave the negative value of -30.031 (KJ/mol) indicating the compound obtained a favourable state in the active site of the protein.
authors.affiliation: 1. Life Science Laboratory, Institute for Computational Science and Technology at Ho Chi Minh City, SBI building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam ; 2. School of Biotechnology, International University - Vietnam National University Ho Chi Minh City, Quarter 6, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Vietnam.
authors.forename: Nhut
authors.initials: N
authors.lastname: Tran
authors.affiliation: 1. Life Science Laboratory, Institute for Computational Science and Technology at Ho Chi Minh City, SBI building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam ; 2. School of Biotechnology, International University - Vietnam National University Ho Chi Minh City, Quarter 6, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Vietnam.
authors.forename: Thanh
authors.initials: T
authors.lastname: Van
authors.affiliation: 1. Life Science Laboratory, Institute for Computational Science and Technology at Ho Chi Minh City, SBI building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam.
authors.forename: Hieu
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: 1. Life Science Laboratory, Institute for Computational Science and Technology at Ho Chi Minh City, SBI building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam ; 2. School of Biotechnology, International University - Vietnam National University Ho Chi Minh City, Quarter 6, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Vietnam.
authors.forename: Ly
authors.initials: L
authors.lastname: Le
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D007251:Influenza, Human; D056004:Molecular Dynamics Simulation; D009439:Neuraminidase / Q000737:chemistry* / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D009439:Neuraminidase
keywords: Influenza virus; binding free energy; molecular dynamic simulation; neuraminidase; virtual screening