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TXD-198 Exhibits Inhibitory Activity Against SARS-CoV-2 by Upregulating ANO1
Ruilin Chen1, Weiya Kong1, Chengyu Li1
1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China.
None:
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.
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