2. Academic Validation
  3. Discovery of Amino Acid-Functionalized Multisubstituted Pyrimidines as Novel Efficient Antiviral Agents Against Enteroviruses

Discovery of Amino Acid-Functionalized Multisubstituted Pyrimidines as Novel Efficient Antiviral Agents Against Enteroviruses

  • J Med Chem. 2026 Feb 12;69(3):2916-2937. doi: 10.1021/acs.jmedchem.5c02792.
Fuqiang Zheng 1 2,  Junkun Ren 1,  Wula Alateng 2,  Hexiang Wang 1,  Liping Duan 3,  Longzhu Bao 1,  Shaoyong Ke 1,  Yanhong Wei 2
Affiliations

Affiliations

  • 1 Key Lab of Microbial Pesticides (Ministry of Agriculture and Rural Affairs), National Biopesticide Engineering Research Centre, Hubei Centre of Technology Innovation for Biopesticide, Hubei Biopesticide Engineering Research Centre, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.
  • 2 National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China.
  • 3 National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai 200025, China.
PMID: 41568669 DOI: 10.1021/acs.jmedchem.5c02792
Abstract

As viral infectious diseases increasingly threaten global health, Antiviral drug research has become a crucial focus in medicinal chemistry, especially enteroviruses are common in summer and autumn, with few specific treatments available. Amino acids are essential for protein formation and biological processes. Novel multisubstituted pyrimidine derivatives with amino acid units were designed and synthesized to evaluate their Antiviral effects against EV71 and CVB3. Compound 8d showed anti-EV71 activity (EC50 = 12.86 ± 0.61 μM), while compound 8e was highly active against CVB3 (EC50 = 11.72 ± 1.01 μM), which primarily acted during the replication stage post-EV71 Infection. Although it did not directly inhibit key viral proteases like 2Apro, 3Cpro, and 3Dpol, it activated the expression of genes related to the cellular type I interferon signaling pathway, enhancing the host's Antiviral defense, which suggests a unique Antiviral mechanism. Our research on amino acid-functionalized pyrimidines has clarified their structure-activity relationships, offering a basis for developing new Antiviral drugs.

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