Exploring the secrets of virus entry: the first respiratory syncytial virus carrying beta lactamase.

Autor:	De Ávila-Arias M; Departamento de Medicina, División Ciencias de la Salud, Universidad del Norte, Barranquilla, Colombia., Villarreal-Camacho JL; Programa de Medicina, Facultad de Ciencias de la Salud, Universidad Libre Seccional Barranquilla, Barranquilla, Colombia., Cadena-Cruz C; Programa de Medicina, Facultad de Ciencias de la Salud, Universidad Libre Seccional Barranquilla, Barranquilla, Colombia., Hurtado-Gómez L; Departamento de Medicina, División Ciencias de la Salud, Universidad del Norte, Barranquilla, Colombia., Costello HM; Genomics Services Laboratory, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., Rodriguez A; Departamento de Medicina, División Ciencias de la Salud, Universidad del Norte, Barranquilla, Colombia., Burgos-Florez F; Programa de regencia en farmacia, grupo de investigación creatividad e innovación tecnológica, Corporación tecnológica Indoamérica, Barranquilla, Colombia.; Escuela de Pregrado, Dirección Académica, Vicerrectoría de Sede, Universidad Nacional de Colombia, Sede La Paz, Cesar, Colombia., Bettin A; Departamento de Medicina, División Ciencias de la Salud, Universidad del Norte, Barranquilla, Colombia., Kararoudi MN; Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., Muñoz A; Departamento de Química y Biología, Universidad del Norte, Barranquilla, Colombia., Peeples ME; Center for Vaccines and Immunity, The Abagail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., San-Juan-Vergara H; Departamento de Medicina, División Ciencias de la Salud, Universidad del Norte, Barranquilla, Colombia.
Jazyk:	angličtina
Zdroj:	Frontiers in microbiology [Front Microbiol] 2024 Feb 16; Vol. 15, pp. 1339569. Date of Electronic Publication: 2024 Feb 16 (Print Publication: 2024).
DOI:	10.3389/fmicb.2024.1339569
Abstrakt:	Background: Respiratory Syncytial Virus (RSV) presents a significant health threat, especially to young children. In-depth understanding of RSV entry mechanisms is essential for effective antiviral development. This study introduces an innovative RSV variant, featuring the fusion of the beta-lactamase (BlaM) enzyme with the RSV-P phosphoprotein, providing a versatile tool for dissecting viral entry dynamics. Methods: Using the AlphaFold2 algorithm, we modeled the tertiary structure of the P-BlaM chimera, revealing structural similarities with both RSV-P and BlaM. Functional assessments, utilizing flow cytometry, quantified beta-lactamase activity and GFP expression in infected bronchial epithelial cells. Western blot analysis confirmed the integrity of P-BlaM within virions. Results: The modeled P-BlaM chimera exhibited structural parallels with RSV-P and BlaM. Functional assays demonstrated robust beta-lactamase activity in recombinant virions, confirming successful P-BlaM incorporation as a structural protein. Quercetin, known for its antiviral properties, impeded viral entry by affecting virion fusion. Additionally, Ulixertinib, an ERK-1/2 inhibitor, significantly curtailed viral entry, implicating ERK-1/2 pathway signaling. Conclusions: Our engineered RSV-P-BlaM chimera emerges as a valuable tool, illuminating RSV entry mechanisms. Structural and functional analyses unveil potential therapeutic targets. Quercetin and Ulixertinib, identified as distinct stage inhibitors, show promise for targeted antiviral strategies. Time-of-addition assays pinpoint quercetin's specific interference stage, advancing our comprehension of RSV entry and guiding future antiviral developments. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 De Ávila-Arias, Villarreal, Cadena-Cruz, Hurtado-Gómez, Costello, Rodriguez, Burgos-Florez, Bettin, Kararoudi, Muñoz, Peeples and San-Juan-Vergara.)
Databáze:	MEDLINE
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