Binding Evolution of the Dengue Virus Envelope Against DC-SIGN: A Combined Approach of Phylogenetics and Molecular Dynamics Analyses Over 30 Years of Dengue Virus in Brazil

Author(s):Show less -

Penteado, Andre Berndt ; Ribeiro, Geovani de Oliveira ; Araujo, Emerson Luiz Lima ; Kato, Rodrigo Bentes ; Freire, Caio Cesar de Melo ; de Araujo, Joselio Maria Galvao ; Wallau, Gabriel da Luz ; Salvato, Richard Steiner ; de Jesus, Ronaldo ; Bosco, Geraldine Goes ; Franz, Helena Ferreira ; da Silva, Pedro Eduardo Almeida ; Leal, Elcio de Souza ; Trossini, Gustavo Henrique Goulart ; Neto, Daniel Ferreira de Lima

• Document type: Journal article
• Source: Journal of Molecular Biology; v. 436, n. 11, p. 26-pg., 2024-05-04.

Abstract

The Red Queen Hypothesis (RQH), derived from Lewis Carroll's "Through the Looking -Glass", postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host -pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus -cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus -host systems and noted patterns of co -evolution. As viruses evolved receptorbinding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co -evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this everevolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time. (c) 2024 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 17/25543-8 - Medicinal Chemistry strategies (LBDD and SBDD) in the search of tripanomatides sirtuin 2 inhibitors
• Grantee: Gustavo Henrique Goulart Trossini
• Support Opportunities: Regular Research Grants