Omicron has reduced the efficacy of vaccines and some monoclonal antibodies. Thus it is of importance to verify the effectiveness of the small molecule drugs targeting the more conserved proteins. A study focused mainly on the drugs that went successfully through the clinical trials like Legevrio by Merck (polymerase inhibitor; molnupiravir) and Paxlovid by Pfizer (protease inhibitor; PF-07321332). Acriflavine was also included which has been proved to be a potent ex vivo and in vivo inhibitor of beta coronaviruses blocking the PLpro protease. Further, remdesivir (sold by Gilead Sciences) (polymerase inhibitor; GS-441524) and AT-527 (by Atea Pharmaceuticals) (polymerase inhibitor; bemnifosbuvir hemisulfate) were included in the panel. 

Antiviral activity of the compounds was tested on subconfluent A549ACE2+TMPRSS2+ cells infected with viruses (all three variants) in the presence of selected concentrations of inhibitors and the cytopathic effect (CPE) was assessed. Also, the half-maximal inhibitory concentration (IC50) value was calculated. Paxlovid, molnupiravir, acriflavine and remdesivir showed the observed inhibition and IC50 similar to the previously described values which were maintained for all the variants. However, the activity of AT-527 was not observed, which may be associated with the model itself and the inability of cells to process the inert pro-drug to its active metabolite.

Summarizing, the obtained results demonstrate that the drugs developed against the SARS-CoV-2 will probably retain their efficacy also for the omicron variant.

SOURCE- bioRxiv 2021.12.21.473268. doi: https://doi.org/10.1101/2021.12.21.473268