2. Academic Validation
  3. 4-(3-Phenylsulfonylindol-2-yl)-1-(pyridin-2-yl)piperazinyl-methanones as Potent Inhibitors of both SARS-CoV-2 and HCoV-OC43 Viruses

4-(3-Phenylsulfonylindol-2-yl)-1-(pyridin-2-yl)piperazinyl-methanones as Potent Inhibitors of both SARS-CoV-2 and HCoV-OC43 Viruses

  • ACS Infect Dis. 2024 Aug 3. doi: 10.1021/acsinfecdis.4c00108.
Michela Puxeddu 1,  Manuela Donalisio 2,  Joachim Jakob Bugert 3,  Angela Corona 4,  Paolo Cocomazzi 5,  Mario Milani 5,  Friederike Hucke 3,  Irene Arduino 2,  Francesca Esposito 4,  Paolo Moretti 6,  Maria Grazia Ortore 6,  Marianna Nalli 1,  Simone Manetto 1,  Giulia Mazzoccanti 1,  Chiara Bigogno 7,  Giulio Dondio 7,  Pietro Sciò 1,  Antonio Coluccia 1,  Matteo Fracella 8,  Guido Antonelli 8,  David Lembo 2,  Enzo Tramontano 4,  Romano Silvestri 1,  Eloise Mastrangelo 5,  Giuseppe La Regina 1
Affiliations

Affiliations

  • 1 Laboratory Affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
  • 2 Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, I-10043 Orbassano, Turin, Italy.
  • 3 Institut für Mikrobiologie der Bundeswehr, Neuherbergstrasse 11, D-80937 München, Germany.
  • 4 Department of Life and Environmental Sciences, University of Cagliari, S.P. 8 Monserrato, Sestu Km 0.700, I-09042 Monserrato, Italy.
  • 5 Biophysics Institute, CNR-IBF, Via Corti 12, I-20133 Milan, Italy.
  • 6 DISVA, Department of Life Sciences and Environment, Università Politecnica delle Marche, Via Brecce Bianche, I-60131 Ancona, Italy.
  • 7 Aphad SrL, Via della Resistenza 65, 20090 Buccinasco, Italy.
  • 8 Laboratory of Virology, Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy.
PMID: 39096289 DOI: 10.1021/acsinfecdis.4c00108
Abstract

SARS-CoV-2 and HCoV-OC43 belong to the same β genus of the Coronaviridae family. SARS-CoV-2 was responsible for the recent COVID-19 pandemic, and HCoV-OC43 is the etiological agent of mild upper respiratory tract infections. SARS-COV-2 and HCoV-OC43 co-infections were found in children with respiratory symptoms during the COVID-19 pandemic. The two β-coronaviruses share a high degree of homology between the 3CLpro active sites, so much so that the safer HCoV-OC43 has been suggested as a tool for the identification of new anti-SARS-COV-2 agents. Compounds 5 and 24 inhibited effectively both Wuhan and British SARS-CoV-2 patient isolates in Vero E6 cells and the HCoV-OC43 in MRC-5 cells at low micromolar concentrations. The inhibition was apparently exerted via targeting the 3CLpro active sites of both viruses. Compounds 5 and 24 at 100 μM inhibited the SARS-CoV-2 3CLpro activity of 61.78 and 67.30%, respectively. These findings highlight 5 and 24 as lead compounds of a novel class of Antiviral agents with the potential to treat SARS-COV-2 and HCoV-OC43 infections.

Keywords

3CL protease; HCoV-OC43; SARS-CoV-2; antiviral drugs; synthesis.

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