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

González-Paz, Lenin, Hurtado-León, María Laura, Lossada, Carla, Fernández-Materán, Francelys V., Vera-Villalobos, Joan, Loroño, Marcos, Paz, J.L., Jeffreys, Laura ORCID: https://orcid.org/0000-0002-0607-6116 and Alvarado, Ysaias J. (2021) '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'. Journal of Molecular Liquids, Vol 340, p. 117284.

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Abstract

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.

Item Type:	Article
Subjects:	QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 250 Anti-infective agents (General) QW Microbiology and Immunology > Viruses > QW 160 Viruses (General). Virology WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 505 Viral respiratory tract infections
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.molliq.2021.117284
Depositing User:	Cathy Waldron
Date Deposited:	30 Sep 2021 14:50
Last Modified:	01 Oct 2021 01:02
URI:	https://archive.lstmed.ac.uk/id/eprint/19053

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