tetano
Editor, Senior Moderator
J Adv Res
. 2023 Oct 4:S2090-1232(23)00294-1.
doi: 10.1016/j.jare.2023.10.002. Online ahead of print. 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[SUP] 1 [/SUP], Ronghui Liang[SUP] 2 [/SUP], Meiling Wu[SUP] 3 [/SUP], Minxiao Yang[SUP] 3 [/SUP], Yubin Xie[SUP] 2 [/SUP], Qing Liu[SUP] 3 [/SUP], Kaiming Tang[SUP] 2 [/SUP], Xiang Ling[SUP] 3 [/SUP], Shuofeng Yuan[SUP] 4 [/SUP], Jiangang Shen[SUP] 5 [/SUP]
Affiliations
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[SUP]+[/SUP] T lymphocytes and CD11b[SUP]+[/SUP] 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; COVID-19; anti-coronavirus; anti-immunoinflammatory activity.
. 2023 Oct 4:S2090-1232(23)00294-1.
doi: 10.1016/j.jare.2023.10.002. Online ahead of print. 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[SUP] 1 [/SUP], Ronghui Liang[SUP] 2 [/SUP], Meiling Wu[SUP] 3 [/SUP], Minxiao Yang[SUP] 3 [/SUP], Yubin Xie[SUP] 2 [/SUP], Qing Liu[SUP] 3 [/SUP], Kaiming Tang[SUP] 2 [/SUP], Xiang Ling[SUP] 3 [/SUP], Shuofeng Yuan[SUP] 4 [/SUP], Jiangang Shen[SUP] 5 [/SUP]
Affiliations
- PMID: 37802148
- DOI: 10.1016/j.jare.2023.10.002
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[SUP]+[/SUP] T lymphocytes and CD11b[SUP]+[/SUP] 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; COVID-19; anti-coronavirus; anti-immunoinflammatory activity.