About: High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses

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About: High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses
Creator	Deng, Yao Tan, Wenjie Wang, Wenling Huang, Baoying Ye, Fei Cen, Shan Niu, Junwei Shen, Liang Wang, Chunhua Wang, Huijuan Zhu, Na
Source	Medline; PMC
abstract	Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we performed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically engineered human CoV OC43 (HCoV-OC43) strain expressing Renilla luciferase (rOC43-ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs in vitro. We screened 56 hits from the HTS data and validated 36 compounds in vitro using wild-type HCoV-OC43. Furthermore, we identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations. Additionally, we found that emetine blocked MERS-CoV entry according to pseudovirus entry assays and that lycorine protected BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This represents the first demonstration of in vivo real-time bioluminescence imaging to monitor the effect of lycorine on the spread and distribution of HCoV-OC43 in a mouse model. These results offer critical information supporting the development of an effective therapeutic strategy against CoV infection. IMPORTANCE Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs in vitro. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.
has issue date	2019-03-27(xsd:dateTime)
bibo:doi	10.1128/jvi.00023-19
bibo:pmid	30918074
has license	green-oa
sha1sum (hex)	8eacedf54b52b89b270a2e148459b6d0ca6898ee
schema:url	https://doi.org/10.1128/jvi.00023-19
resource representing a document's title	High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses
has PubMed Central identifier	PMC6613765
has PubMed identifier	30918074
schema:publication	Journal of Virology
resource representing a document's body	covid:8eacedf54b52b89b270a2e148459b6d0ca6898ee#body_text
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