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World J Virol. Dec 25, 2024; 13(4): 99110
Published online Dec 25, 2024. doi: 10.5501/wjv.v13.i4.99110
Viral-host molecular interactions and metabolic modulation: Strategies to inhibit flaviviruses pathogenesis
Zeeshan Ahmad Khan, Mukesh Kumar Yadav, Dong-Woo Lim, Hojun Kim, Jing-Hua Wang, AbuZar Ansari
Zeeshan Ahmad Khan, Biohealth Products Research Center (BPRC), Research Center for Aged-life Redesign (RCAR), Department of Physical Therapy, INJE University, Gimhae 5084, South Korea
Mukesh Kumar Yadav, Department of Microbiology, Central University of Punjab, Bathinda 151401, India
Dong-Woo Lim, Department of Diagnostics, College of Korean Medicine, Dongguk University, Goyang 10326, South Korea
Hojun Kim, Division of Rehabilitation Medicine of Korean Medicine, Department of Oriental Rehabilitation Medicine, Dongguk University, Ilsan Hospital, Goyang 10326, South Korea
Jing-Hua Wang, Institute of Oriental Medicine, Dongguk University, Goyang 10326, South Korea
AbuZar Ansari, Department of Obstetrics and Gynecology, Ewha Womans University, Seoul 07985, South Korea
Co-first authors: Zeeshan Ahmad Khan and Mukesh Kumar Yadav.
Co-corresponding authors: Jing-Hua Wang and AbuZar Ansari.
Author contributions: Ansari A, Yadav MK, and Wang JH were responsible for conceptualization; Khan Z, Yadav MK, Kim H, and Lim DW were responsible for writing review and editing; Khan Z, Yadav MK, and Lim DW were responsible for visualization; Ansari A and Wang JH were responsible for supervision; all the authors have read and approved the final version of the manuscript.
Supported by The South Korea Health Technology R and D Project through the South Korea Health Industry Development Institute, Funded by the Ministry of Health and Welfare, South Korea, No. HF20C0020.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: AbuZar Ansari, MPhil, PhD, Research Professor, Department of Obstetrics and Gynecology, Ewha Womans University, 529 Seongsan-ro, Seoul 07985, South Korea. abu.kim.0313@gmail.com
Received: July 14, 2024
Revised: August 16, 2024
Accepted: August 27, 2024
Published online: December 25, 2024
Processing time: 95 Days and 18.2 Hours
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; Nonstructural proteins; Virus-host interaction; Metabolism; Inhibitors; Vaccines

Core Tip: Targeting host metabolic molecules and interactions shows promise for combating flavivirus infections but has limitations such as potential off-target effects, disruption of essential cellular functions, and virus resistance. A viral-host interactome can elucidate complex interactions, guiding anti-flavivirus drug and vaccine development. By inhibiting metabolic signaling, researchers can disrupt viral replication, entry, and assembly, increasing the likelihood of effective antiviral agents. This approach is key for developing treatments despite its challenges.