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The influenza H1N1 virus is the causative agent of the flu pandemic in the world. Due to the shortage of effective means of control, it is remained the serious threats to public and avian health. To battle the surge of viral outbreaks, new treatments are crucially needed. The viral RNA polymerase, which is responsible for transcription and replication of the RNA genome, is comprised of subunits PA, PB1 and PB2. PA has endonuclease activity and is a well known target for inhibitor and drug design. In the current study, we employed molecular docking, molecular dynamics (MD), MMPBSA, QMMM and ADME studies to find and propose an inhibitor among 11,873 structures against PA. Our molecular docking, MD, MMPBSA and QMMM studies showed that ZINC15340668 has ideal characteristics as a potent PA inhibitor, and can be used in experimental phase and further development. Also, ADME prediction demonstrated that all physico-chemical parameters are within the acceptable range defined for human use. Molecular mechanism based study revealed that upon inhibitor binding; the flexibility of PA backbone is increased. This observation demonstrates the plasticity of PA active site, and it should be noticed in drug design against PA Influenza A viruses. In the final phase of the study, the efficiency of our proposed hit was tested computationally against mutant drug resistant I38T_PA. Our results exhibited that the hit inhibits the I38T_PA in different manner with high potency., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Recently, the quick spreads of broad-spectrum beta-lactams antibiotic resistance in pathogenic strains of bacteria have become a major global health problem. These new emerging resistances cause ineffectiveness of antibiotics and increasing the severity of diseases and treatment costs. Among different and diverse resistance targets, we chose a class A beta lactamase, CTX-M-9, with the aim of identifying new chemical entities to be used for further rational drug design. Based on this purpose, a set of 5000 molecules from the Zinc database have been screened by docking experiments using AutoDock Vina software. The best ranked compound, with respect of the previously proved inhibitor compound 19, was further tested by molecular dynamics (MD) simulation. Our molecular modeling analysis demonstrates that ZINC33264777 has ideal characteristics a potent beta lactamase CTX-M-9 inhibitor. In the free form of beta lactamase, NMR relaxation studies showed the extensive motions near the active site and in the Ω-loop. However, our molecular dynamics studies revealed that in the compound 1: beta lactamase complex, the flexibility of Ω-loop was restricted., (Copyright © 2017 Elsevier Ltd. All rights reserved.)