Elsevier

Antiviral Research

Volume 208, December 2022, 105428
Antiviral Research

Astersaponin I from Aster koraiensis is a natural viral fusion blocker that inhibits the infection of SARS-CoV-2 variants and syncytium formation

https://doi.org/10.1016/j.antiviral.2022.105428Get rights and content

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.

Keywords

SARS-CoV-2 variants
COVID-19
Astersaponin I
Aster koraiensis
Membrane fusion
Syncytium

Abbreviations

AI
Astersaponin I
AK
Aster koraiensis
COVID-19
coronavirus disease 2019
ACE2
angiotensin converting enzyme 2
SARS-CoV-2
Severe acute respiratory syndrome coronavirus-2

Data availability

Data will be made available on request.

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1

These authors equally contributed to this work.

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