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

Lenin González-Paz, María Laura Hurtado-León, Carla Lossada, Francelys V. Fernández-Materán, Joan Vera-Villalobos, Marcos Loroño, J. L. Paz, Laura Jeffreys, Ysaias J. Alvarado

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

Resumen

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.

Idioma originalInglés
Número de artículo117284
PublicaciónJournal of Molecular Liquids
Volumen340
DOI
EstadoPublicada - 15 oct 2021

Nota bibliográfica

Publisher Copyright:
© 2021 Elsevier B.V.

Huella

Profundice en los temas de investigación de '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'. En conjunto forman una huella única.

Citar esto