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Article: Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters

TitleMetallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters
Authors
Issue Date2020
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nmicrobiol/
Citation
Nature Microbiology, 2020, v. 5 n. 11, p. 1439-1448 How to Cite?
AbstractSARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality1. 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 of Helicobacter pylori infection, 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 µM) and DNA-unwinding (IC50 = 0.70 µM) 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.
Persistent Identifierhttp://hdl.handle.net/10722/290054
ISSN
2023 Impact Factor: 20.5
2023 SCImago Journal Rankings: 7.982
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYuan, S-
dc.contributor.authorWang, R-
dc.contributor.authorChan, JFW-
dc.contributor.authorZhang, AJ-
dc.contributor.authorCheng, T-
dc.contributor.authorChik, KKH-
dc.contributor.authorYe, ZW-
dc.contributor.authorWang, S-
dc.contributor.authorLee, ACY-
dc.contributor.authorJin, L-
dc.contributor.authorLi, H-
dc.contributor.authorJin, DY-
dc.contributor.authorYuen, KY-
dc.contributor.authorSun, H-
dc.date.accessioned2020-10-22T08:21:26Z-
dc.date.available2020-10-22T08:21:26Z-
dc.date.issued2020-
dc.identifier.citationNature Microbiology, 2020, v. 5 n. 11, p. 1439-1448-
dc.identifier.issn2058-5276-
dc.identifier.urihttp://hdl.handle.net/10722/290054-
dc.description.abstractSARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality1. 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 of Helicobacter pylori infection, 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 µM) and DNA-unwinding (IC50 = 0.70 µM) 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.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nmicrobiol/-
dc.relation.ispartofNature Microbiology-
dc.rightsThis is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: https://doi.org/[insert DOI]-
dc.titleMetallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters-
dc.typeArticle-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailWang, R: u3002771@connect.hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailZhang, AJ: zhangajx@hkucc.hku.hk-
dc.identifier.emailYe, ZW: zwye@hku.hk-
dc.identifier.emailJin, L: ljjin@hkucc.hku.hk-
dc.identifier.emailJin, DY: dyjin@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailSun, H: hsun@hku.hk-
dc.identifier.authorityYuan, S=rp02640-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityZhang, AJ=rp00413-
dc.identifier.authorityJin, L=rp00028-
dc.identifier.authorityJin, DY=rp00452-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authoritySun, H=rp00777-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41564-020-00802-x-
dc.identifier.pmid33028965-
dc.identifier.scopuseid_2-s2.0-85092147330-
dc.identifier.hkuros316414-
dc.identifier.volume5-
dc.identifier.issue11-
dc.identifier.spage1439-
dc.identifier.epage1448-
dc.identifier.isiWOS:000576097800001-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2058-5276-

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