Antiviral and anti-inflammatory effects of Tabamide A derivative, TA25, against human rhinovirus and multiple zoonotic viruses in vitro and in silico

Human rhinovirus (HRV), first isolated in 1956, belongs to the family Picornaviridae. HRV causes mild cold and severe respiratory disease. To date, no FDA-approved antiviral or anti-inflammatory drugs are available. TA25 is a phenolic amide derivative extracted from Nicotiana tabacum. To investigate the potential candidate for antiviral therapeutics, we evaluated the antiviral potency of TA25 for HRV and multiple zoonotic viruses. The antiviral and anti-inflammatory effects were evaluated using RT-qPCR and RNA-seq. Strand-specific RT-qPCR was performed to measure genomic and anti-genomic RNA expression after TA25 treatment. In addition, an AI-based docking test was conducted to investigate the binding affinity of TA25 with viral proteins. TA25 induced significant reduction in viral replication and suppressed the expression of pro-inflammatory genes. Inhibition of viral replication by TA25 treatment was confirmed by strand-specific RT-qPCR. TA25 showed broad-spectrum antiviral activity against multiple viruses, including HRV-1A, ZIKV, DENV, VACV, and IBV. Using AI-driven structure-based docking analysis, TA25 showed strongest binding affinity with HRV 2B protein. This study demonstrates that TA25 confers the broad antiviral and anti-inflammatory activity against HRV and multiple zoonotic viruses. These findings provide valuable insights into antiviral strategies of TA25 for a promising therapeutic candidate in response to emerging RNA and DNA viruses. Overall design: Innate immune and pro-inflammatory genes expression profiling analysis of total RNA-seq data from HeLa, HRV-infected HeLa or HRV-infected and 30 µM of TA25-treated HeLa cells. Samples were colleted at 48 hpi.