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Virol J . Calceolarioside B inhibits SARS-CoV-2 Omicron BA.2 variant cell entry and modulates immune response

tetano

Editor, Senior Moderator
Virol J


. 2024 Dec 21;21(1):329.
doi: 10.1186/s12985-024-02566-w. Calceolarioside B inhibits SARS-CoV-2 Omicron BA.2 variant cell entry and modulates immune response

Xiao-Bin Lin[SUP] #[/SUP][SUP] 1 [/SUP], Yu-Zhi Yao[SUP] #[/SUP][SUP] 1 2 [/SUP], Qi-Rong Wen[SUP] 3 [/SUP], Fu-Bin Liu[SUP] 4 [/SUP], Yuan-Xuan Cai[SUP] 1 [/SUP], Rui-Hong Chen[SUP] 5 [/SUP], Jin Han[SUP] 6 [/SUP]



Affiliations
Abstract

This study evaluated the inhibitory effects of calceolarioside B, extracted from the traditional Chinese herb Mutong (Akebia quinata Thumb), on the SARS-CoV-2 Omicron BA.2 variant. Molecular docking and molecular dynamics simulations predicted the binding sites and interactions between calceolarioside B and the Omicron BA.2 spike (S) protein. Biolayer interferometry (BLI) and immunofluorescence assays validated its high-affinity binding. Pseudovirus entry assays assessed the inhibitory effects of calceolarioside B on viral entry into host cells, while enzyme-linked immunosorbent assay (ELISA) measured inflammatory cytokine levels. Flow cytometry was used to analyze its effects on macrophage phenotype switching. Results demonstrated that calceolarioside B could bind to the Omicron BA.2 S protein with high affinity, and significantly inhibited viral entry into host cells by interfering with the binding of angiotensin-converting enzyme 2 (ACE2) receptor and S protein. Additionally, calceolarioside B reduced IL(interleukin)-6 expression levels and promoted the switch of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. These findings suggest that calceolarioside B possesses antiviral and immunomodulatory effects, making it a potential dual-function inhibitor for the treatment of COVID-19.

Keywords: Calceolarioside B; Immunomodulation; Molecular docking; SARS-CoV-2 Omicron BA.2; Viral inhibition.

 
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