Antiviral Activity of N 1 ,N 3 -Disubstituted Uracil Derivatives against SARS-CoV-2 Variants of Concern.
Andrei E SiniavinMikhail S NovikovVladimir A GushchinAlexander A TerechovIgor A IvanovMaria P ParamonovaElena S GureevaLeonid I RussuNadezhda A KuznetsovaElena V ShidlovskayaSergei I LuyksaarDaria V VasinaSergei A ZolotovNailya A ZigangirovaDenis Y LogunovAlexander L GintsburgPublished in: International journal of molecular sciences (2022)
Despite the widespread use of the COVID-19 vaccines, the search for effective antiviral drugs for the treatment of patients infected with SARS-CoV-2 is still relevant. Genetic variability leads to the continued circulation of new variants of concern (VOC). There is a significant decrease in the effectiveness of antibody-based therapy, which raises concerns about the development of new antiviral drugs with a high spectrum of activity against VOCs. We synthesized new analogs of uracil derivatives where uracil was substituted at the N 1 and N 3 positions. Antiviral activity was studied in Vero E6 cells against VOC, including currently widely circulating SARS-CoV-2 Omicron. All synthesized compounds of the panel showed a wide antiviral effect. In addition, we determined that these compounds inhibit the activity of recombinant SARS-CoV-2 RdRp. Our study suggests that these non-nucleoside uracil-based analogs may be of future use as a treatment for patients infected with circulating SARS-CoV-2 variants.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- copy number
- end stage renal disease
- induced apoptosis
- coronavirus disease
- randomized controlled trial
- stem cells
- ejection fraction
- systematic review
- gene expression
- chronic kidney disease
- genome wide
- endoplasmic reticulum stress
- cell proliferation
- current status
- solid state