Susceptibility of inhibitors against 3C protease of coxsackievirus A16 and enterovirus A71 causing hand, foot and mouth disease: A molecular dynamics study
| Autor: | Nawee Kungwan, Supot Hannongbua, Bodee Nutho, W. Jetsadawisut, Arthitaya Meeprasert, Peter Wolschann, Thanyada Rungrotmongkol |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Proteases Phenylalanine media_common.quotation_subject 030106 microbiology Biophysics In Vitro Techniques Molecular Dynamics Simulation Biochemistry Coxsackievirus a16 Hand-foot-and-mouth disease Microbiology Viral Proteins 03 medical and health sciences stomatognathic system medicine Humans Enzyme Inhibitors 3c protease Enterovirus media_common Drug candidate Chemistry Organic Chemistry 3C Viral Proteases Valine Isoxazoles Enterovirus a71 medicine.disease Cysteine protease Virology Pyrrolidinones Enterovirus A Human Cysteine Endopeptidases Drug Design Hand Foot and Mouth Disease Peptides Oligopeptides Protein Binding |
| Zdroj: | Biophysical Chemistry. 219:9-16 |
| ISSN: | 0301-4622 |
| DOI: | 10.1016/j.bpc.2016.09.005 |
| Popis: | Hand foot and mouth disease (HFMD) epidemic has occurred in many countries. Coxsackievirus A16 (CV-A16) and Enterovirus A71 (EV-A71) are the main causes of HFMD. Up to now, there are no anti-HFMD drugs available. Rupintrivir, a broad-spectrum inhibitor, is a drug candidate for HFMD treatment, while other HFMD inhibitors designed from several studies have a relatively low efficiency. Therefore, in this work we aim to study the binding mechanisms of rupintrivir and a peptidic α,β-unsaturated ethyl ester (SG85) against both CV-A16 and EV-A71 3C proteases (3Cpro) using all-atoms molecular dynamics simulation. The obtained results indicate that SG85 shows a stronger binding affinity than rupintrivir against CV-A16. Both inhibitors exhibit a comparable affinity against EV-A71 3Cpro. The molecular information of the binding of the two inhibitors to the proteases will be elucidated. Thus, it is implied that these two compounds may be used as leads for further anti-HFMD drug design and development. |
| Databáze: | OpenAIRE |
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