Research progress on the mechanism of nucleoside antiviral drugs
10.11665/j.issn.1000-5048.2025041201
- VernacularTitle:核苷类抗病毒药物的作用机制研究进展
- Author:
Mengting LIU
1
;
Yifan ZHU
;
Zi 'an WANG
;
Yicheng JIA
;
Huixian WANG
;
Xingru HE
Author Information
1. 杭州师范大学药学院, 杭州311121
- Publication Type:Journal Article 期刊文章
- Keywords:
nucleoside drugs;
mechanism of action;
polymerase;
prodrug;
antiviral
- From:
Journal of China Pharmaceutical University
2025;56(6):678-688
- CountryChina
- Language:Chinese
-
Abstract:
As an important strategy in antiviral drug development, nucleoside analogs (NAs) have attracted considerable attention due to their unique mechanisms of action and favorable safety profile. This review systematically summarizes recent advances in the mechanisms of action of NAs, focusing on the following four aspects: (1) Targeting viral polymerases, inhibiting viral replication through mechanisms such as non-absolute termination, delayed chain termination and induction of viral RNA mutations in addition to classical chain termination, which has been newly discovered; (2) Regulating RNA methylation modifications—for instance, competitively inhibiting methyltransferases, which significantly reduces viral replication efficiency; (3) Depleting nucleotide pools—by affecting host cell purine nucleotide synthesis pathways, thereby indirectly inhibiting viral replication; and (4) Immunomodulatory functions—including activation of the STING pathway to promote interferon production. Furthermore, this review systematically discusses the breakthrough progress in prodrug technologies for addressing key clinical challenges such as drug resistance and off-target toxicity of NAs. These advances provide crucial technical support for the clinical translation of NAs. These advances provide key technical support for the clinical translation of NAs. This review clarifies the multi-target action rules of NAs and provides a theoretical framework for the design of next-generation broad-spectrum antiviral agents.
