Mary Wilson
Well-known member
This is an uncorrected proof.
Accepted: January 18, 2023;
Published: January 26, 2023
https://doi.org/10.1371/journal.ppat.1011131
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, [ ... ],Xianghui Fu [ view all]
Abstract
The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011131
Accepted: January 18, 2023;
Published: January 26, 2023
https://doi.org/10.1371/journal.ppat.1011131
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, [ ... ],Xianghui Fu [ view all]
Abstract
The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011131