Alisol B 23-acetate broadly inhibits coronavirus through blocking virus entry and suppresses proinflammatory T cells responses for the treatment of COVID-19

Qiaohui Du; Ronghui Liang; Meiling Wu; Minxiao Yang; Yubin Xie; Qing Liu; Kaiming Tang; Xiang Lin; Shuofeng Yuan; Jiangang Shen

doi:10.1016/j.jare.2023.10.002

Alisol B 23-acetate broadly inhibits coronavirus through blocking virus entry and suppresses proinflammatory T cells responses for the treatment of COVID-19

J Adv Res. 2023 Oct 4:S2090-1232(23)00294-1. doi: 10.1016/j.jare.2023.10.002. Online ahead of print.

Authors

Qiaohui Du¹, Ronghui Liang², Meiling Wu³, Minxiao Yang³, Yubin Xie², Qing Liu³, Kaiming Tang², Xiang Lin³, Shuofeng Yuan⁴, Jiangang Shen⁵

Affiliations

¹ School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 3 Sassoon Road, Pokfulam, Hong Kong, Hong Kong Special Administrative Region; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Pokfulam, Hong Kong, Hong Kong Special Administrative Region.
² State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
³ School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 3 Sassoon Road, Pokfulam, Hong Kong, Hong Kong Special Administrative Region.
⁴ State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region; Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China. Electronic address: yuansf@hku.hk.
⁵ School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 3 Sassoon Road, Pokfulam, Hong Kong, Hong Kong Special Administrative Region; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Pokfulam, Hong Kong, Hong Kong Special Administrative Region. Electronic address: shenjg@hku.hk.

PMID: 37802148
DOI: 10.1016/j.jare.2023.10.002

Abstract

Introduction: Emerging severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 causes a global health disaster and pandemic. Seeking effective anti-pan-CoVs drugs benefit critical illness patients of coronavirus disease 2019 (COVID-19) but also may play a role in emerging CoVs of the future.

Objectives: This study tested the hypothesis that alisol B 23-acetate could be a viral entry inhibitor and would have proinflammatory inhibition for COVID-19 treatment.

Methods: SARS-CoV-2 and its variants infected several cell lines were applied to evaluate the anti-CoVs activities of alisol B 23-aceate in vitro. The effects of alisol B 23-acetate on in vivo models were assessed by using SARS-CoV-2 and its variants challenged hamster and human angiotensin-converting enzyme 2 (ACE2) transgenic mice. The target of alisol B 23-acetate to ACE2 was analyzed using hydrogen/deuterium exchange (HDX) mass spectrometry (MS).

Results: Alisol B 23-acetate had inhibitory effects on different species of coronavirus. By using HDX-MS, we found that alisol B 23-acetate had inhibition potency toward ACE2. In vivo experiments showed that alisol B 23-acetate treatment remarkably decreased viral copy, reduced CD4⁺ T lymphocytes and CD11b⁺ macrophages infiltration and ameliorated lung damages in the hamster model. In Omicron variant infected human ACE2 transgenic mice, alisol B 23-acetate effectively alleviated viral load in nasal turbinate and reduced proinflammatory cytokines interleukin 17 (IL17) and interferon γ (IFNγ) in peripheral blood. The prophylactic treatment of alisol B 23-acetate by intranasal administration significantly attenuated Omicron viral load in the hamster lung tissues. Moreover, alisol B 23-acetate treatment remarkably inhibited proinflammatory responses through mitigating the secretions of IFNγ and IL17 in the cultured human and mice lymphocytes in vitro.

Conclusion: Alisol B 23-acetate could be a promising therapeutic agent for COVID-19 treatment and its underlying mechanisms might be attributed to viral entry inhibition and anti-inflammatory activities.

Keywords: ACE2; Alisol B 23-acetate; Anti-coronavirus; Anti-immunoinflammatory activity; COVID-19.