Viral-host molecular interactions and metabolic modulation: Strategies to inhibit flaviviruses pathogenesis

Abstract

Flaviviruses, which include globally impactful pathogens, such as West Nile virus, yellow fever virus, Zika virus, Japanese encephalitis virus, and dengue virus, contribute significantly to human infections. Despite the ongoing emergence and resurgence of flavivirus-mediated pathogenesis, the absence of specific therapeutic options remains a challenge in the prevention and treatment of flaviviral infections. Through the intricate processes of fusion, transcription, replication, and maturation, the complex interplay of viral and host metabolic interactions affects pathophysiology. Crucial interactions involve metabolic molecules, such as amino acids, glucose, fatty acids, and nucleotides, each playing a pivotal role in the replication and maturation of flaviviruses. These viral-host metabolic molecular interactions hijack and modulate the molecular mechanisms of host metabolism. A comprehensive understanding of these intricate metabolic pathways offers valuable insights, potentially unveiling novel targets for therapeutic interventions against flaviviral pathogenesis. This review emphasizes promising avenues for the development of therapeutic agents that target specific metabolic molecules, such as amino acids, glucose, fatty acids, and nucleotides, which interact with flavivirus replication and are closely linked to the modulation of host metabolism. The clinical limitations of current drugs have prompted the development of new inhibitory strategies for flaviviruses based on an understanding of the molecular interactions between the virus and the host.

Keywords: Flavivirus; Inhibitors; Metabolism; Nonstructural proteins; Vaccines; Virus-host interaction.

Figure 1

Flavivirus structural features. NS: Nonstructural.

Figure 2

Flavivirus mechanism of infection to host cell. PH: Pondus hydrogenii; DC-Sign: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin.

Figure 3

Flavivirus-host metabolic interaction and associated therapeutics targets. Protein-protein metabolic interaction, carbohydrate metabolic interaction, lipid metabolic interaction, nucleotide metabolic interaction associated therapeutic strategy. PH: Pondus hydrogenii; DC-Sign: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; FASN: Fatty acid synthase; ATP: Adenosine triphosphate; COA: Coenzyme A; TCA: Tricarboxylic acid; SCD: Sperm chromatin dispersion; SFA: Saturated fatty acid; MUFA: Monounsaturated fatty acid; CPT: Camptothecin; HMG: 3-hydroxy-3-methylglutaryl.