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

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.