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

被引：1

作者：

Du, Qiaohui ^{[1
,2
]}

Liang, Ronghui ^{[3
]}

Wu, Meiling ^{[1
]}

Yang, Minxiao ^{[1
]}

Xie, Yubin ^{[3
]}

Liu, Qing ^{[1
]}

Tang, Kaiming ^{[3
]}

Lin, Xiang ^{[1
]}

Yuan, Shuofeng ^{[3
,4
,5
]}

Shen, Jiangang ^{[1
,2
]}

机构：

[1] Univ Hong Kong, Li Ka Shing Fac Med, Sch Chinese Med, Pokfulam, 3 Sassoon Rd, Hong Kong, Peoples R China

[2] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Pokfulam, Hong Kong, Peoples R China

[3] Univ Hong Kong, State Key Lab Emerging Infect Dis, Dept Microbiol, Li Ka Shing Fac Med,Pokfulam, Hong Kong, Peoples R China

[4] Hong Kong Sci & Technol Pk, Ctr Virol Vaccinol & Therapeut, Hong Kong, Peoples R China

[5] Univ Hong Kong, Dept Clin Microbiol & Infect Control, Shenzhen Hosp, Shenzhen, Guangdong, Peoples R China

来源：

JOURNAL OF ADVANCED RESEARCH | 2024年 / 62卷

关键词：

Alisol B 23-acetate; Anti-coronavirus; COVID-19 Anti-immunoinflammatory activity ACE2; RESPIRATORY SYNDROME CORONAVIRUS; RHIZOMA-ALISMATIS; INFECTION; PNEUMONIA; ORIENTALE; EXTRACT; VARIANT; ACE2;

D O I：

10.1016/j.jare.2023.10.002

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 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 c (IFNc) 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 IFNc 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. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article

引用

页码：273 / 290

页数：18