Targeting G-quadruplex in SARS-CoV-2 RNA Genome with Tetraphenylethene Derivatives for Antiviral Therapy

Targeting genomic RNA conformations that are crucial for SARS-CoV-2 replication is a promising antiviral strategy. Herein we have developed tetraphenylethene (TPE) derivatives to target RNA G-quadruplexes (RGQs) present in the SARS-CoV-2 nucleocapsid gene ORF. Our EMSA, fluorescence and CD data suggests the binding of two TPE derivatives i.e., TPE−MePy and TPE-AllylPy, with RGQ derived from SARS-CoV-2 nucleocapsid gene. In addition, in vitro luciferase assay demonstrated suppression in translation efficiency by 3.86-fold and 2.89-fold in presence of TPE-MePy and TPE-AllylPy, respectively. Subsequently, the cytotoxicity and immunofluorescence-based antiviral assay in VeroE6 cells indicated 82% inhibition in SARS-CoV-2 nucleocapsid gene expression without any effect on cell viability. These results highlight the promising use of TPE derivatives as an antiviral drug to alter the crucial genes expression in SARS-CoV-2 as well as other viruses.