期刊
NATURE MICROBIOLOGY
卷 5, 期 11, 页码 1439-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41564-020-00802-x
关键词
-
类别
资金
- Research Grants Council (RGC) [R707018]
- HKSAR of China [2020YFA0707500, 2020YFA0707504]
- National Key R&D Programmes of China [2020YFA0707500, 2020YFA0707504]
- University of Hong Kong (HKU) Seed Fund for Basic Research [201909185060]
Drug used to treatHelicobacter pyloriinfection reduces SARS-CoV-2 viral loads in lungs and alleviates virus-associated pneumonia in a golden Syrian hamster model. SARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality(1). Currently, therapeutic options for COVID-19 are limited. Historically, metal compounds have found use as antimicrobial agents, but their antiviral activities have rarely been explored. Here, we test a set of metallodrugs and related compounds, and identify ranitidine bismuth citrate, a commonly used drug for the treatment ofHelicobacter pyloriinfection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo. Ranitidine bismuth citrate exhibited low cytotoxicity and protected SARS-CoV-2-infected cells with a high selectivity index of 975. Importantly, ranitidine bismuth citrate suppressed SARS-CoV-2 replication, leading to decreased viral loads in both upper and lower respiratory tracts, and relieved virus-associated pneumonia in a golden Syrian hamster model. In vitro studies showed that ranitidine bismuth citrate and its related compounds exhibited inhibition towards both the ATPase (IC50 = 0.69 mu M) and DNA-unwinding (IC50 = 0.70 mu M) activities of the SARS-CoV-2 helicase via an irreversible displacement of zinc(ii) ions from the enzyme by bismuth(iii) ions. Our findings highlight viral helicase as a druggable target and the clinical potential of bismuth(iii) drugs or other metallodrugs for the treatment of SARS-CoV-2 infection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据