Structural deformability induced in proteins of potential interest associated with COVID-19 by binding of homologues present in ivermectin: Comparative study based in elastic networks models
| Autor: | María Laura Hurtado-León, Ysaias Alvarado, Francelys V. Fernández-Materán, Joan Vera-Villalobos, Marcos Loroño, José Luis Paz, Carla A. Lossada, Laura Jeffreys, Lenin A. González-Paz |
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| Rok vydání: | 2021 |
| Předmět: |
2019-20 coronavirus outbreak
Coronavirus disease 2019 (COVID-19) ENM Elastic Network Models Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) NMA Normal Mode Analysis Article Turn (biochemistry) SPECTRUS SPECTral-based Rigid Units Subdivision Ivermectin Materials Chemistry medicine CG Coarse-Grained GNM Gaussian Network Model Physical and Theoretical Chemistry SWAXS Small- and Wide-Angle X-ray Scattering curves Elastic network models NMA Spectroscopy Chemistry SARS-CoV-2 Condensed Matter Physics Atomic and Molecular Physics and Optics In vitro Electronic Optical and Magnetic Materials ANM Anisotropic Network Models ANM PSN Protein Structure Network Intramolecular force Biophysics GNM medicine.drug ENM |
| Zdroj: | Journal of Molecular Liquids |
| ISSN: | 0167-7322 |
| Popis: | The COVID-19 pandemic has accelerated the study of the potential of multi-target drugs (MTDs). The mixture of homologues called ivermectin (avermectin-B1a + avermectin-B1b) has been shown to be a MTD with potential antiviral activity against SARS-CoV-2 in vitro. However, there are few reports on the effect of each homologue on the flexibility and stiffness of proteins associated with COVID-19, described as ivermectin targets. We observed that each homologue was stably bound to the proteins studied and was able to induce detectable changes with Elastic Network Models (ENM). The perturbations induced by each homologue were characteristic of each compound and, in turn, were represented by a disruption of native intramolecular networks (interactions between residues). The homologues were able to slightly modify the conformation and stability of the connection points between the Cα atoms of the residues that make up the structural network of proteins (nodes), compared to free proteins. Each homologue was able to modified differently the distribution of quasi-rigid regions of the proteins, which could theoretically alter their biological activities. These results could provide a biophysical-computational view of the potential MTD mechanism that has been reported for ivermectin. |
| Databáze: | OpenAIRE |
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