4.7 Article

The inhibition effects and mechanisms of sulfated chitooligosaccharides on influenza A virus in vitro and in vivo

Journal

CARBOHYDRATE POLYMERS
Volume 286, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2022.119316

Keywords

Influenza A virus Sulfated chitooligosaccharide; Adsorption; Membrane fusion; HA protein; Sulfated chitooligosaccharide

Funding

  1. National Natural Science Foundation of China [82173860, 81874320]
  2. NSFC-Shandong Joint Fund [U1706210]
  3. Shandong Province Major Science and Technology Innovation Project Special [2018SDKJ0404-2]
  4. Shandong Provincial Natural Science Foundation [ZR2019ZD18, ZR2017MH013]

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Sulfated chitooligosaccharide demonstrates broad-spectrum anti-influenza A virus activity and low toxicity, with sulfation modification enhancing its antiviral effects.
Sulfated chitooligosaccharide was reported to possess inhibition effect on human immunodeficiency virus (HIV) entry into host cells. Herein, we prepared chitooligosaccharide COS and its sulfate derivative SCOS and explored whether the sulfation modification can enhance the anti-influenza A virus (IAV) activity of COS. Interestingly, we discovered that SCOS possessed broad-spectrum anti-IAV effects with low toxicity, while the non-sulfated chitooligosaccharide COS had very low inhibition on IAV, verifying that the sulfation modification is essential for the anti-IAV actions of chitooligosaccharide. SCOS may target virus hemagglutinin (HA) protein to block both virus adsorption and membrane fusion processes. Oral administration of SCOS significantly decreased pulmonary viral titers and improved survival rate in IAV infected mice, comparable to the effects of Oseltamivir. Therefore, our findings support further studies on the use of SCOS as a novel entry inhibitor for IAV and as a supplement to current therapeutics for influenza.

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