tetano
Editor, Senior Moderator
Eur J Med Chem
. 2021 Dec 11;229:114046.
doi: 10.1016/j.ejmech.2021.114046. Online ahead of print.
Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL [SUP]pro[/SUP] covalent inhibitors
Julia K Stille[SUP] 1 [/SUP], Jevgenijs Tjutrins[SUP] 1 [/SUP], Guanyu Wang[SUP] 1 [/SUP], Felipe A Venegas[SUP] 1 [/SUP], Christopher Hennecker[SUP] 1 [/SUP], Andrés M Rueda[SUP] 1 [/SUP], Itai Sharon[SUP] 2 [/SUP], Nicole Blaine[SUP] 1 [/SUP], Caitlin E Miron[SUP] 1 [/SUP], Sharon Pinus[SUP] 1 [/SUP], Anne Labarre[SUP] 1 [/SUP], Jessica Plescia[SUP] 1 [/SUP], Mihai Burai Patrascu[SUP] 1 [/SUP], Xiaocong Zhang[SUP] 1 [/SUP], Alexander S Wahba[SUP] 1 [/SUP], Danielle Vlaho[SUP] 1 [/SUP], Mitchell J Huot[SUP] 1 [/SUP], T Martin Schmeing[SUP] 2 [/SUP], Anthony K Mittermaier[SUP] 3 [/SUP], Nicolas Moitessier[SUP] 4 [/SUP]
Affiliations
Abstract
Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CL[SUP]pro[/SUP] (main coronaviruses cysteine-protease) has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CL[SUP]pro[/SUP] non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL[SUP]pro[/SUP]. We report herein our efforts in the design and synthesis of submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.
Keywords: 3CLpro; Mpro; SARS-CoV2; covalent inhibitors.
. 2021 Dec 11;229:114046.
doi: 10.1016/j.ejmech.2021.114046. Online ahead of print.
Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL [SUP]pro[/SUP] covalent inhibitors
Julia K Stille[SUP] 1 [/SUP], Jevgenijs Tjutrins[SUP] 1 [/SUP], Guanyu Wang[SUP] 1 [/SUP], Felipe A Venegas[SUP] 1 [/SUP], Christopher Hennecker[SUP] 1 [/SUP], Andrés M Rueda[SUP] 1 [/SUP], Itai Sharon[SUP] 2 [/SUP], Nicole Blaine[SUP] 1 [/SUP], Caitlin E Miron[SUP] 1 [/SUP], Sharon Pinus[SUP] 1 [/SUP], Anne Labarre[SUP] 1 [/SUP], Jessica Plescia[SUP] 1 [/SUP], Mihai Burai Patrascu[SUP] 1 [/SUP], Xiaocong Zhang[SUP] 1 [/SUP], Alexander S Wahba[SUP] 1 [/SUP], Danielle Vlaho[SUP] 1 [/SUP], Mitchell J Huot[SUP] 1 [/SUP], T Martin Schmeing[SUP] 2 [/SUP], Anthony K Mittermaier[SUP] 3 [/SUP], Nicolas Moitessier[SUP] 4 [/SUP]
Affiliations
- PMID: 34995923
- PMCID: PMC8665847
- DOI: 10.1016/j.ejmech.2021.114046
Abstract
Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CL[SUP]pro[/SUP] (main coronaviruses cysteine-protease) has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CL[SUP]pro[/SUP] non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL[SUP]pro[/SUP]. We report herein our efforts in the design and synthesis of submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.
Keywords: 3CLpro; Mpro; SARS-CoV2; covalent inhibitors.