Targeting RNA G-quadruplex with repurposed drugs blocks SARS-CoV-2 entry

• DOI: 10.1371/journal.ppat.1011131
• Publication Date: 2023-01-26T18:50:24Z
• Authors: Qiyu Tong; Geng Liu; Xiongbo Sang; Xinyue Zhu; Xiaoli Fu; Chao Dou; Yue Jian; Jiani Zhang; Sailan Zou; Guixiang Zhang; Xiao Du; Dan Liu; Shiqian Qi; Wei Cheng; Yan Tian; Xianghui Fu
• Keywords: Repurposing; Furin; Drug repositioning

The rapid emergence of SARS-CoV-2 variants concern, the complexity infection, and functional redundancy host factors, underscore an urgent need for broad-spectrum antivirals against continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report potential RNA G-quadruplex (RG4)-targeting strategy entry. Combining bioinformatics, biochemical biophysical approaches, characterize existence RG4s in several factors. In silico screening followed by experimental validation identify Topotecan (TPT) Berbamine (BBM), two clinical approved drugs, RG4-stabilizing agents COVID-19. Both TPT BBM can reduce protein level RG4-containing including ACE2, AXL, FURIN, TMPRSS2. Intriguingly, block pseudovirus entry into target cells vitro murine tissues vivo . These findings emphasize significance RG4 pathogenesis provide antiviral prevention treatment.