TXD-198 Exhibits Inhibitory Activity Against SARS-CoV-2 by Upregulating ANO1.

The continuous global health challenge posed by the novel coronavirus SARS-CoV-2 emphasizes the urgent demand for effective antiviral therapies. This study discovers TXD-198 as a potent inhibitor of SARS-CoV-2 infection. Through a transcription- and replication-competent virus-like particle (trVLP) system, it's shown that TXD-198 efficiently suppresses viral activity with an IC50 of 1.04 μM and a high selectivity index of 42.55. Validation in two distinct pseudoviral models-the replication-competent rVSV-Venus-VSV∆G-SARS2-S∆21 system and SARS-CoV-2 spike-pseudotyped lentiviral system (PSVs) further confirmed TXD-198's antiviral ability. Transcriptomic analysis reveals that TXD-198 exerts antiviral effects through a dual mechanism of direct viral inhibition and anti-inflammatory activity. Notably, TXD-198 significantly upregulates the expression of the ANO1 gene, and knocking down ANO1 reverses the antiviral effect of TXD-198, indicating ANO1's crucial role in TXD-198's antiviral action. These findings suggest TXD-198 is a promising therapeutic candidate for COVID-19 treatment related to ANO1, calling for further exploration of its clinical potential.