Molecular modeling simulation studies reveal new potential inhibitors against HPV E6 protein

Joel Ricci-Lopez (2019, [Artículo])

High-risk strains of human papillomavirus (HPV) have been identified as the etiologic agent of some anogenital tract, head, and neck cancers. Although prophylactic HPV vaccines have been approved; it is still necessary a drug-based treatment against the infection and its oncogenic effects. The E6 oncoprotein is one of the most studied therapeutic targets of HPV, it has been identified as a key factor in cell immortalization and tumor progression in HPV-positive cells. E6 can promote the degradation of p53, a tumor suppressor protein, through the interaction with the cellular ubiquitin ligase E6AP. Therefore, preventing the formation of the E6-E6AP complex is one of the main strategies to inhibit the viability and proliferation of infected cells. Herein, we propose an in silico pipeline to identify small-molecule inhibitors of the E6-E6AP interaction. Virtual screening was carried out by predicting the ADME properties of the molecules and performing ensemble-based docking simulations to E6 protein followed by binding free energy estimation through MM/PB(GB)SA methods. Finally, the top-three compounds were selected, and their stability in the E6 docked complex and their effect in the inhibition of the E6-E6AP interaction was corroborated by molecular dynamics simulation. Therefore, this pipeline and the identified molecules represent a new starting point in the development of anti-HPV drugs. © 2019 Ricci-López et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ligand, luteolin, protein E6, protein inhibitor, ubiquitin protein ligase, ubiquitin protein ligase E6AP, unclassified drug, antivirus agent, DNA binding protein, E6 protein, Human papillomavirus type 18, oncoprotein, protein binding, protein p53, TP CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA

Contrabando y redes de negocios : Hispanoamérica en el comercio global, 1610-1814

Guillermina del Valle Pavón (2023, [Libro])

"Las colaboraciones que integran este libro colectivo profundizan en el análisis de algunos circuitos comerciales, que fueron claves en el juego de intercambios en Nueva España, Perú, las Filipinas, La Habana y Buenos Aires, en el arco temporal que se extiende de 1610 a 1814."

Hispanoamérica (Antiguo Régimen); Nueva España (Virreinato); Comercio; Comercio mundial; Comerciantes; Contrabando; Corrupción; Empresas; Mercantilismo; Monarquía hispánica; Mercaderes; Redes de negocios; Argentina; Estudios de caso; Siglos XVII-XIX; CIENCIAS SOCIALES HISTORIA HISTORIA POR ESPECIALIDADES HISTORIA POR ESPECIALIDADES

Effect of antimicrobial nanocomposites on Vibrio cholerae lifestyles: Pellicle biofilm, planktonic and surface-attached biofilm

ANAID MEZA VILLEZCAS (2019, [Artículo])

Vibrio cholerae is an important human pathogen causing intestinal disease with a high incidence in developing countries. V. cholerae can switch between planktonic and biofilm lifestyles. Biofilm formation is determinant for transmission, virulence and antibiotic resistance. Due to the enhanced antibiotic resistance observed by bacterial pathogens, antimicrobial nanomaterials have been used to combat infections by stopping bacterial growth and preventing biofilm formation. In this study, the effect of the nanocomposites zeolite-embedded silver (Ag), copper (Cu), or zinc (Zn) nanoparticles (NPs) was evaluated in V. cholerae planktonic cells, and in two biofilm states: pellicle biofilm (PB), formed between air-liquid interphase, and surface-attached biofilm (SB), formed at solid-liquid interfaces. Each nanocomposite type had a distinctive antimicrobial effect altering each V. cholerae lifestyles differently. The ZEO-AgNPs nanocomposite inhibited PB formation at 4 μg/ml, and prevented SB formation and eliminated planktonic cells at 8 μg/ml. In contrast, the nanocomposites ZEO-CuNPs and ZEO-ZnNPs affect V. cholerae viability but did not completely avoid bacterial growth. At transcriptional level, depending on the nanoparticles and biofilm type, nanocomposites modified the relative expression of the vpsL, rbmA and bap1, genes involved in biofilm formation. Furthermore, the relative abundance of the outer membrane proteins OmpT, OmpU, OmpA and OmpW also differs among treatments in PB and SB. This work provides a basis for further study of the nanomaterials effect at structural, genetic and proteomic levels to understand the response mechanisms of V. cholerae against metallic nanoparticles. © 2019 Meza-Villezcas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

bacterial protein, copper nanoparticle, nanocomposite, OmpT protein, OmpU protein, OmpW protein, outer membrane protein A, silver nanoparticle, unclassified drug, zeolite, zinc nanoparticle, antiinfective agent, copper, metal nanoparticle, nanocompos BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA MICROBIOLOGÍA MICROBIOLOGÍA