Kim, Tai Young Kim, Ji-Young Kwon, Hak Cheol Jeon, Sangeun Lee, Sol ji Jung, Haejin Kim, Seungtaek Jang, Dae Sik Lee, C Justin 2024-01-12T02:34:14Z 2024-01-12T02:34:14Z 2022-11-30 2022-12 0166-3542 https://pubs.kist.re.kr/handle/201004/75888 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. English Elsevier BV Astersaponin I from Aster koraiensis is a natural viral fusion blocker that inhibits the infection of SARS-CoV-2 variants and syncytium formation Article 10.1016/j.antiviral.2022.105428 1 Antiviral Research, v.208, pp.1 - 13 Antiviral Research 208 1 13 N scie scopus 000903285700002 Pharmacology & Pharmacy Virology Pharmacology & Pharmacy Virology Article OMICRON REPLICATION PATHOLOGY MEDICINE EVASION SARS-CoV-2 variants COVID-19 Astersaponin I Aster koraiensis Membrane fusion Syncytium