1. 4-(3-Phenylsulfonylindol-2-yl)-1-(pyridin-2-yl)piperazinyl-methanones as Potent Inhibitors of both SARS-CoV-2 and HCoV-OC43 Viruses.
- Author
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Puxeddu M, Donalisio M, Bugert JJ, Corona A, Cocomazzi P, Milani M, Hucke F, Arduino I, Esposito F, Moretti P, Ortore MG, Nalli M, Manetto S, Mazzoccanti G, Bigogno C, Dondio G, Sciò P, Coluccia A, Fracella M, Antonelli G, Lembo D, Tramontano E, Silvestri R, Mastrangelo E, and La Regina G
- Subjects
- Humans, Chlorocebus aethiops, Animals, Vero Cells, Coronavirus 3C Proteases antagonists & inhibitors, COVID-19 Drug Treatment, COVID-19 virology, Cell Line, SARS-CoV-2 drug effects, Antiviral Agents pharmacology, Antiviral Agents chemistry, Antiviral Agents chemical synthesis, Coronavirus OC43, Human drug effects, Coronavirus OC43, Human physiology
- 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.
- Published
- 2024
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