Molecular modeling and lead design of substituted zanamivir derivatives as potent anti-influenza drugs

BMC Bioinformatics

Research

Salma Jamal¹  Sukriti Goyal¹  Asmita Das²  Dhwani Dholakia²  Aditi Singh³  Abhinav Grover⁴ 

[1]Department of Bioscience and Biotechnology, Banasthali University, 304022, Tonk, Rajasthan, India

[2]Department of Biotechnology, Delhi Technological University, 110042, New Delhi, India

[3]Department of Biotechnology, TERI University, 110070, New Delhi, India

[4]School of Biotechnology, Jawaharlal Nehru University, 110067, New Delhi, India

关键词: Neuraminidase;    H1N1;    H3N2;    NA;    Influenza;    QSAR;   

DOI  :  10.1186/s12859-016-1374-1

来源: Springer

【 摘 要 】

BackgroundInfluenza virus spreads infection by two main surface glycoproteins, namely hemagglutinin (HA) and neuraminidase (NA). NA cleaves the sialic acid receptors eventually releasing newly formed virus particles which then invade new cells. Inhibition of NA could limit the replication of virus to one round which is insufficient to cause the disease.ResultsAn experimentally reported series of acylguanidine zanamivir derivatives was used to develop GQSAR model targeting NA in different strains of influenza virus, H1N1 and H3N2. A combinatorial library was developed and their inhibitory activities were predicted using the GQSAR model.ConclusionThe top leads were analyzed by docking which revealed the binding modes of these inhibitors in the active site of NA (150-loop). The top compound (AMA) was selected for carrying out molecular dynamics simulations for 15 ns which provided insights into the time dependent dynamics of the designed leads. AMA possessed a docking score of −8.26 Kcal/mol with H1N1 strain and −7.00 Kcal/mol with H3N2 strain. Ligand-bound complexes of both H1N1 and H3N2 were observed to be stable for 11 ns and 7 ns respectively. ADME descriptors were also calculated to study the pharmacokinetic properties of AMA which revealed its drug-like properties.

【 授权许可】

CC BY   
© The Author(s). 2016