韓国で自生する植物から抗ウイルス物質を発見(Antiviral substances discovered within native plants in South Korea)

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TOmicronを含むSARS-CoV-2亜種の細胞侵入能力を阻害する効果が高い2種類のサポニンを同定した wo saponins were identified to be highly effective in blocking the ability of SARS-CoV-2 variants including Omicron to enter the cells

2022-11-11 大韓民国・基礎科学研究院(IBS)

ノテガシワと高麗人(コリアンダー)、韓国固有の植物から新しい抗ウイルス化合物を発見した。研究チームは、これらの植物に含まれるサポニンが、ウイルスが宿主細胞に侵入するための膜融合を阻害することにより、SARS-CoV-2感染を抑制することに特に有効であることを発見した。
研究チームは、前述の2つの植物に含まれる2つのが、このコロナウイルスとヒト細胞間の膜融合を阻害し、ウイルスが宿主に感染する経路をすべて効果的に遮断できることを明らかにした。
研究チームはまず、ACE2受容体タンパク質を過剰発現したヒト肺細胞と、比較的制約の少ないバイオセーフティレベル2の研究施設で使用できる、ウイルススパイクタンパク質を表面に発現した疑似ウイルスを使って、SARS-CoV-2感染モデルを作製した。この細胞をアステルサポニンIとランセマサイドAで処理し、化合物のウイルス感染抑制効果を検証した。両サポニンのIC50値(半値最大阻害濃度)は2μMであり、コロナウイルスの細胞内への侵入を阻止する効果が高いことがわかった。その後の実際の本物のコロナウイルスを用いた実験でも同様の結果が確認され、ほぼ同じ効率で感染が抑制された。さらに重要なことは、その抑制効果がオミクロンなどすべてのSARS-CoV-2亜種で同じであったことである。

<関連情報>

Aster koraiensis由来のAstersaponin Iは、SARS-CoV-2亜種の感染とシンシチウム形成を阻害する天然のウイルス融合ブロッカーである Astersaponin I from Aster koraiensis is a natural viral fusion blocker that inhibits the infection of SARS-CoV-2 variants and syncytium formation

Tai Young Kim,Ji-Young Kim,Hak Cheol Kwon,Sangeun Jeon,Sol ji Lee,Haejin Jung,Seungtaek Kim,Dae Sik Jang,C Justin Lee
Antiviral Research  Available online 15 October 2022
DOI:https://doi.org/10.1016/j.antiviral.2022.105428

Fig. 1

Abstract

The continuous emergence of SARS-CoV-2 variants prolongs COVID-19 pandemic. Although SARS-CoV-2 vaccines and therapeutics are currently available, there is still a need for development of safe and effective drugs against SARS-CoV-2 and also for preparedness for the next pandemic. Here, we discover that astersaponin I (AI), a triterpenoid saponin in Aster koraiensis inhibits SARS-CoV-2 entry pathways at the plasma membrane and within the endosomal compartments mainly by increasing cholesterol content in the plasma membrane and interfering with the fusion of SARS-CoV-2 envelope with the host cell membrane. Moreover, we find that this functional property of AI as a fusion blocker enables it to inhibit the infection with SARS-CoV-2 variants including the Alpha, Beta, Delta, and Omicron with a similar efficacy, and the formation of syncytium, a multinucleated cells driven by SARS-CoV-2 spike protein-mediated cell-to-cell fusion. Finally, we claim that the triterpene backbone as well as the attached hydrophilic sugar moieties of AI are structurally important for its inhibitory activity against the membrane fusion event. Overall, this study demonstrates that AI is a natural viral fusion inhibitor and proposes that it can be a broad-spectrum antiviral agent against current COVID-19 pandemic and future outbreaks of novel viral pathogens.

SARS-CoV-2に対するサポニン系膜融合阻害剤の合成と構造活性相関研究 Synthesis and structure–activity relationship study of saponin-based membrane fusion inhibitors against SARS-CoV-2

YounghoJ ang,Tai Young Kim,Sangeun Jeon,Hyeonggeun Lim,Jin AhLee,Seungtaek Kim,C.Justin Lee,Sunkyu Han
Bioorganic Chemistry  Available online: 26 June 2022
DOI:https://doi.org/10.1016/j.bioorg.2022.105985

Highlights:

•SAR studies of synthetic saponins regarding their inhibition of SARS-CoV-2′s cell entry.
•Development of two minimal synthetic saponins (19 and 20) that are equipotent to platycodin D.
•Our newly developed saponin derivatives prevent the fusion between the virus and host cell membranes.
•Effectiveness of our newly developed saponin based antiviral agents against all known variants of SARS-CoV-2.

Abstract

We previously discovered that triterpenoid saponin platycodin D inhibits the SARS-CoV-2 entry to the host cell. Herein, we synthesized various saponin derivatives and established a structure–activity relationship of saponin-based antiviral agents against SARS-CoV-2. We discovered that the C3-glucose, the C28-oligosaccharide moiety that consist of (→3)-β-d-Xyl-(1 → 4)-α-l-Rham-(1 → 2)-β-d-Ara-(1 → ) as the last three sugar units, and the C16-hydroxyl group were critical components of saponin-based coronavirus cell entry inhibitors. These findings enabled us to develop minimal saponin-based antiviral agents that are equipotent to the originally discovered platycodin D. We found that our saponin-based antiviral agents inhibited both the endosomal and transmembrane protease serine 2-mediated cell surface viral entries. Cell fusion assay experiment revealed that our newly developed compounds inhibit the SARS-CoV-2 entry by blocking the fusion between the viral and host cell membranes. The effectiveness of the newly developed antiviral agents over various SARS-CoV-2 variants hints at the broad-spectrum antiviral efficacy of saponin-based therapeutics against future coronavirus variants.

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有機化学・薬学
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