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

Puxeddu M.;Donalisio M.;Bugert J. J.;Corona Angela;Cocomazzi P.;Milani M.;Hucke F.;Arduino I.;Esposito Francesca;Moretti P.;Ortore M. G.;Nalli M.;Manetto S.;Mazzoccanti G.;Bigogno C.;Dondio G.;Scio P.;Coluccia A.;Fracella M.;Antonelli G.;Lembo D.;Tramontano Enzo;Silvestri R.;Mastrangelo E.;La Regina G.

2024-01-01

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Abstract

SARS-CoV-2 and HCoV-OC43 belong to the same beta 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 beta-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 mu M 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.