Éric Marsault (1971–2021): A Legacy through the Prism of Relationship Chemistry

Sarret, Philippe

doi:10.1021/acs.jmedchem.1c00481

Cited by 7 publications

(4 citation statements)

References 32 publications

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“…We recognize the help of the RNomics Platform of the Université de Sherbrooke. We dedicate this work to the memory of Professor Eric Marsault 67 . This work was supported by operating grants from the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding program of the Canadian Institutes of Health Research (CIHR) (UBR 322812; VR3-172639 (R.L., P.L.B.…”

Section: Acknowledgementsmentioning

confidence: 99%

A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic

Shapira

Monreal

Dion

et al. 2022

Nature

161

126

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The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced owing to emerging variants of concern1,2. Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against variants of concern3,4. Attractive pharmacological targets to impede viral entry include type-II transmembrane serine proteases (TTSPs) such as TMPRSS2; these proteases cleave the viral spike protein to expose the fusion peptide for cell entry, and thus have an essential role in the virus lifecycle5,6. Here we identify and characterize a small-molecule compound, N-0385, which exhibits low nanomolar potency and a selectivity index of higher than 106 in inhibiting SARS-CoV-2 infection in human lung cells and in donor-derived colonoids7. In Calu-3 cells it inhibits the entry of the SARS-CoV-2 variants of concern B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta). Notably, in the K18-human ACE2 transgenic mouse model of severe COVID-19, we found that N-0385 affords a high level of prophylactic and therapeutic benefit after multiple administrations or even after a single administration. Together, our findings show that TTSP-mediated proteolytic maturation of the spike protein is critical for SARS-CoV-2 infection in vivo, and suggest that N-0385 provides an effective early treatment option against COVID-19 and emerging SARS-CoV-2 variants of concern.

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Section: Acknowledgementsmentioning

confidence: 99%

A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic

Shapira

Monreal

Dion

et al. 2022

Nature

161

126

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“…and M.A-M. reviewed the manuscript and provided comments. The authors gratefully acknowledge and dedicate this article to Prof. Éric Marsault, who passed away 51 . Marilène Paquette (Histology Core, University of Sherbrooke) is gratefully acknowledged for her assistance with the histology technics.…”

Section: Discussionmentioning

confidence: 99%

Apelin improves angiogenesis and blood flow reperfusion following lower limb ischemia in diabetic mice

Robillard

Tran

Brazeau

et al. 2023

Preprint

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Objective: Peripheral artery disease (PAD) is a major risk factor for lower-extremity amputation in diabetic patients caused by an insufficient angiogenic response. Unfortunately, therapeutic angiogenesis using growth factors, such as the vascular endothelial growth factor (VEGF), are ineffective in diabetic conditions due to diabetes-induced growth factor resistance. The apelinergic system (APJ receptor/apelin) is highly upregulated under hypoxic condition and acts as an activator of angiogenesis. Apelin treatment has been shown to improve revascularization in nondiabetic models of ischemia, however, its role on angiogenesis in diabetic conditions remains poorly investigated. Thus, this study explored the impact of Pyr-apelin-13 in endothelial cell function and diabetic mouse model of hindlimb ischemia. Approach and Results: Nondiabetic and diabetic mice underwent femoral artery ligation to induce lower limb ischemia. A group of diabetic mice was implanted subcutaneously with osmotic pumps delivering Pyr-apelin-13 for 28 days. Blood flow reperfusion was measured for 4 weeks post-surgery and exercise willingness was assessed in individual cages with voluntary wheels. In vitro, BAECs were exposed to normal (NG) or high glucose (HG) levels and hypoxia. Cell migration, proliferation and tube formation assays were performed following either VEGF or Pyr-apelin-13 stimulation. Following limb ischemia, blood flow reperfusion, functional recovery of the limb and vascular density were improved in diabetic mice receiving Pyr-apelin-13 compared to untreated diabetic mice. In cultured BAECs, exposure to HG concentrations and hypoxia reduced VEGF proangiogenic actions, whereas apelin proangiogenic effects remained unaltered. Pyr-apelin-13 induced its proangiogenic actions through Akt/AMPK/eNOS and RhoA/ROCK signaling pathways under both NG or HG concentrations and hypoxia exposure. Conclusion: Pyr-apelin-13 promoted endothelial cell function and angiogenesis in the ischemic limb despite diabetes and HG level exposure. Therefore, our results identified the apelinergic system as a potential therapeutic target for angiogenic therapy in diabetic patients with PAD.

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“…The authors gratefully acknowledge and dedicate this article to ÉM, who passed away ( 58 ). Marilène Paquette (Histology Core, University of Sherbrooke) is gratefully acknowledged for her assistance with the histology technics.…”

Section: Acknowledgmentsmentioning

confidence: 99%

Apelin prevents diabetes-induced poor collateral vessel formation and blood flow reperfusion in ischemic limb

Robillard

Tran

Lachance

et al. 2023

Front. Cardiovasc. Med.

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IntroductionPeripheral arterial disease (PAD) is a major risk factor for lower-extremity amputation in diabetic patients. Unfortunately, previous clinical studies investigating therapeutic angiogenesis using the vascular endothelial growth factor (VEGF) have shown disappointing results in diabetic patients, which evokes the necessity for novel therapeutic agents. The apelinergic system (APJ receptor/apelin) is highly upregulated under hypoxic condition and acts as an activator of angiogenesis. Apelin treatment improves revascularization in nondiabetic models of ischemia, however, its role on angiogenesis in diabetic conditions remains poorly investigated. This study explored the impact of Pyr-apelin-13 in endothelial cell function and diabetic mouse model of hindlimb ischemia.MethodsNondiabetic and diabetic mice underwent femoral artery ligation to induce limb ischemia. Diabetic mice were implanted subcutaneously with osmotic pumps delivering Pyr-apelin-13 for 28 days. Blood flow reperfusion was measured for 4 weeks post-surgery and exercise willingness was assessed with voluntary wheels. In vitro, bovine aortic endothelial cells (BAECs) were exposed to normal (NG) or high glucose (HG) levels and hypoxia. Cell migration, proliferation and tube formation assays were performed following either VEGF or Pyr-apelin-13 stimulation.Results and DiscussionFollowing limb ischemia, blood flow reperfusion, functional recovery of the limb and vascular density were improved in diabetic mice receiving Pyr-apelin-13 compared to untreated diabetic mice. In cultured BAECs, exposure to HG concentrations and hypoxia reduced VEGF proangiogenic actions, whereas apelin proangiogenic effects remained unaltered. Pyr-apelin-13 induced its proangiogenic actions through Akt/AMPK/eNOS and RhoA/ROCK signaling pathways under both NG or HG concentrations and hypoxia exposure. Our results identified the apelinergic system as a potential therapeutic target for angiogenic therapy in diabetic patients with PAD.

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Éric Marsault (1971–2021): A Legacy through the Prism of Relationship Chemistry

Cited by 7 publications

References 32 publications

A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic

A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic

Apelin improves angiogenesis and blood flow reperfusion following lower limb ischemia in diabetic mice

Apelin prevents diabetes-induced poor collateral vessel formation and blood flow reperfusion in ischemic limb

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Éric Marsault (1971–2021): A Legacy through the Prism of Relationship Chemistry

Cited by 7 publications

References 32 publications

A﻿ TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic

A﻿ TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic

Apelin improves angiogenesis and blood flow reperfusion following lower limb ischemia in diabetic mice

Apelin prevents diabetes-induced poor collateral vessel formation and blood flow reperfusion in ischemic limb

Contact Info

Product

Resources

About

A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic

A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic