By Pooja Toshniwal PahariaSep 21 2022Reviewed by Danielle Ellis, B.Sc. In a recent study published in PLoS Pathogens, researchers described a novel antiviral mechanism of action for an FDA -approved thiopurine known as 6-thioguanine .
About the study The present study investigated whether 6-TG and other thiopurines could interfere with coronavirus glycoproteins. Further, SARS-CoV-2 S was ectopically expressed and assessed against multiple 6-TG concentrations, following which immunoblotting analysis with pseudovirions was performed. S-expressing 293T cell lysates were treated with PNGase F to eliminate N-linked glycans from polypeptide chains, and the effects of 6-TG on the secretory pathway were assessed by Gaussia luciferase assays.
Results Genetics & Genomics eBook Compilation of the top interviews, articles, and news in the last year.6-TG inhibited the initial stage of SARS-CoV-2 and HCoV-OC43 replication, limiting full-length viral genome, structural proteins and subgenomic RNA accumulation. Ectopic S expression analysis showed enhanced S protein electrophoretic mobility from several βCoVs by 6-TG treatment, in accordance with the in vitro enzymatic N-linked oligosaccharide elimination from the S protein.
Putative full-length genomic viral RNA was reduced by 10-fold in most stages of infection. 6-TG treatment caused similar reductions in viral S- and N-encoding sub-genomic RNA correlating with lower protein accumulation. Immunostaining HCoV-OC43-infected cells with anti-N antibodies showed punctate staining initially and peripheral staining subsequently. Post-6-TG treatment, the stained areas were brighter, with large puncta observed after 24 hours post-infection .