A Heparan Sulfate Mimetic RAFT Copolymer Inhibits SARS-CoV-2 Infection and Ameliorates Viral-Induced Inflammation.

Autor: Ling J; Department of Medical Biochemistry and Microbiology, The Biomedical Center, Uppsala University, Uppsala, 75123, Sweden.; Zoonosis Science Center, Uppsala University, Uppsala, 75123, Sweden., Lundkvist Å; Department of Medical Biochemistry and Microbiology, The Biomedical Center, Uppsala University, Uppsala, 75123, Sweden.; Zoonosis Science Center, Uppsala University, Uppsala, 75123, Sweden., Guerrini M; Istituto Di Ricerche Chimiche e Biochimiche G. Ronzoni, Milan, 20133, Italy., Ferro V; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, 4072, Australia., Li JP; Department of Medical Biochemistry and Microbiology, The Biomedical Center, Uppsala University, Uppsala, 75123, Sweden.; SciLifeLab Uppsala, Uppsala University, Uppsala, 75123, Sweden., Li J; Department of Medical Biochemistry and Microbiology, The Biomedical Center, Uppsala University, Uppsala, 75123, Sweden.; Zoonosis Science Center, Uppsala University, Uppsala, 75123, Sweden.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Dec 16, pp. e2411737. Date of Electronic Publication: 2024 Dec 16.
DOI: 10.1002/advs.202411737
Abstrakt: The high transmissibility and mutation ability of coronaviruses enable them to easily escape existing immune protection and also pose a challenge to existing antiviral drugs. Moreover, drugs only targeting viruses cannot always attenuate the "cytokine storm". Herein, a synthetic heparan sulfate (HS) mimetic, HMSA-06 is reported, that exhibited antiviral activities against both the SARS-CoV-2 prototype and Omicron strains by targeting viral entry and replication. Of particular note, HMSA-06 demonstrated more potent anti-SARS-CoV-2 effects than PG545 and Roneparstat. SARS-CoV-2 is reported to hijack autophagy to facilitate its replication, therefore boosting autophagy can attenuate SARS-CoV-2 infection. It is revealed that HMSA-06, but not a similar HS mimetic that failed to inhibit SARS-CoV-2, can upregulate cellular autophagy flux. In addition, HMSA-06 was found to robustly block the NLRP3-mediated inflammatory reaction in SARS-CoV-2 infected THP-1 derived macrophages as evidenced by a reduction in inflammasome formation and the subsequent decreased secretion of mature caspase-1 and IL-1β. The HMSA-06's inflammation inhibitory function is further confirmed using a LPS/ATP-stimulated THP-1 macrophage model. Altogether, this study has identified a promising HS mimetic to combat SARS-CoV-2-associated diseases by inhibiting viral infection and attenuating viral-induced inflammatory reaction, providing insights into the development of novel anti-coronavirus drugs in the future.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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