Anti-enterovirus 71 activity of native fucosylated chondroitin sulfates and their derivatives

• Published in: Carbohydrate polymers Vol. 346; p. 122657
• Main Authors: Niu, Qingfeng, Zhou, Han, Ma, Xiaoyao, Jiang, Yuanyuan, Liu, Chanjuan, Wang, Wei, Yu, Guangli, Li, Guoyun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.12.2024
• Subjects: Animals; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antiviral effect; Chlorocebus aethiops; Chondroitin Sulfates - chemistry; Chondroitin Sulfates - pharmacology; Enterovirus 71; Enterovirus A, Human - drug effects; Fucosylated chondroitin sulfate; Humans; Molecular Weight; Sea Cucumbers - chemistry; Structure elucidation; Structure-Activity Relationship; Vero Cells; Enterovirus 71; Antiviral effect; Structure elucidation; Structure-activity relationship; Fucosylated chondroitin sulfate
• ISSN: 0144-8617; 1879-1344; 1879-1344
• DOI: 10.1016/j.carbpol.2024.122657

Enterovirus 71 (EV71) is recognized as a major causative agent of hand, foot, and mouth disease (HFMD), posing a significant global public health concern due to its widespread impact and resulting in a major public health issue worldwide. Despite its prevalence, current clinical therapy lacks effective antiviral agents. Fucosylated chondroitin sulfates (FCS) derived from sea cucumber exhibits a range of biological activities including potent antiviral effects. This study provides compelling evidence of the potent antiviral efficacy of FCS against EV71. To further elucidate the impact of structural variations on the anti-EV71 activity, native FCSs with diverse sulfation patterns and a varity of FCS derivatives were prepared and analyzed. Notably, this study presents the detailed structural characterization of FCSs from the sea cucumbers Holothuria scabra Jaege and Holothuria fuscopunctata. Analysis of the structure-activity relationships revealed that molecular weight, sulfated fucose branches, and sulfation pattern were all crucial factors contributing to the potent inhibitory effects of FCS against EV71. Interestingly, molecular weight emerged as the most significant structural determinant of the antiviral potency. These findings suggest the promising potential of utilizing FCS as an innovative EV71 entry inhibitor for the treatment of HFMD. [Display omitted]