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Biophysical chemistry
11, 2021;278 106677.

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach.

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
Author Information
  1. Lenin González-Paz: Universidad del Zulia (LUZ), Facultad Experimental de Ciencias (FEC), Departamento de Biología, Laboratorio de Genética y Biología Molecular (LGBM), 4001 Maracaibo, Venezuela; Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Estudios Botánicos y Agroforestales (CEBA), Laboratorio de Protección Vegetal (LPV), 4001 Maracaibo, Venezuela. Electronic address: lgonzalezpaz@gmail.com.
  2. María Laura Hurtado-León: Universidad del Zulia (LUZ), Facultad Experimental de Ciencias (FEC), Departamento de Biología, Laboratorio de Genética y Biología Molecular (LGBM), 4001 Maracaibo, Venezuela.
  3. Carla Lossada: Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Investigación y Tecnología de Materiales (CITeMA), Laboratorio de Caracterización Molecular y Biomolecular, 4001 Maracaibo, Venezuela.
  4. Francelys V Fernández-Materán: Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Investigación y Tecnología de Materiales (CITeMA), Laboratorio de Caracterización Molecular y Biomolecular, 4001 Maracaibo, Venezuela.
  5. Joan Vera-Villalobos: Facultad de Ciencias Naturales y Matemáticas, Departamento de Química y Ciencias Ambientales, Laboratorio de Análisis Químico Instrumental (LAQUINS), Escuela Superior Politécnica del Litoral, Guayaquil, Ecuador.
  6. Marcos Loroño: Departamento Académico de Química Analítica e Instrumental, Facultad de Química e Ingeniería Química, Universidad Nacional Mayor de San Marcos, Lima, Peru.
  7. J L Paz: Departamento Académico de Química Inorgánica, Facultad de Química e Ingeniería Química, Universidad Nacional Mayor de San Marcos, Lima, Peru.
  8. Laura Jeffreys: Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
  9. Ysaias J Alvarado: Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Investigación y Tecnología de Materiales (CITeMA), Laboratorio de Caracterización Molecular y Biomolecular, 4001 Maracaibo, Venezuela. Electronic address: alvaradoysaias@gmail.com.
PMID: 34428682 DOI: 10.1016/j.bpc.2021.106677

Abstract

The SARS-CoV-2 pandemic has accelerated the study of existing drugs. The mixture of homologs called ivermectin (avermectin-B1a [HB1a] + avermectin-B1b [HB1b]) has shown antiviral activity against SARS-CoV-2 in vitro. However, there are few reports on the behavior of each homolog. We investigated the interaction of each homolog with promising targets of interest associated with SARS-CoV-2 infection from a biophysical and computational-chemistry perspective using docking and molecular dynamics. We observed a differential behavior for each homolog, with an affinity of HB1b for viral structures, and of HB1a for host structures considered. The induced disturbances were differential and influenced by the hydrophobicity of each homolog and of the binding pockets. We present the first comparative analysis of the potential theoretical inhibitory effect of both avermectins on biomolecules associated with COVID-19, and suggest that ivermectin through its homologs, has a multiobjective behavior.

Keywords

Avermectin COVID-19 Ivermectin Molecular docking Molecular dynamic SARS-CoV-2

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MeSH Term

Animals
Antiviral Agents
Binding Sites
COVID-19
Coronavirus 3C Proteases
DNA Helicases
Humans
Ivermectin
Kinetics
Mice
Molecular Docking Simulation
Molecular Dynamics Simulation
Protein Binding
Protein Conformation
Protein Interaction Domains and Motifs
SARS-CoV-2
Thermodynamics
alpha Karyopherins
beta Karyopherins
COVID-19 Drug Treatment

Chemicals

Antiviral Agents
KPNB1 protein, human
alpha Karyopherins
beta Karyopherins
karyopherin alpha 2
Ivermectin
avermectin
Coronavirus 3C Proteases
DNA Helicases
Comparative Study Journal Article
Article has an altmetric score of 12

Word Cloud

Created with Highcharts 10.0.0SARS-CoV-2homologivermectinbehaviorassociatedstudyhomologsinteractioninterestbiophysicaldockingdifferentialstructuresCOVID-19Molecularpandemicacceleratedexistingdrugsmixturecalledavermectin-B1a[HB1a] + avermectin-B1b[HB1b]shownantiviralactivityvitroHoweverreportsinvestigatedpromisingtargetsinfectioncomputational-chemistryperspectiveusingmoleculardynamicsobservedaffinityHB1bviralHB1ahostconsideredinduceddisturbancesinfluencedhydrophobicitybindingpocketspresentfirstcomparativeanalysispotentialtheoreticalinhibitoryeffectavermectinsbiomoleculessuggestmultiobjectiveComparativeproteinsSARS-CoV-2:computationalapproachAvermectinIvermectindynamic

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