3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice.
Sci Transl Med
; 12(557)2020 08 19.
Article
in English
| MEDLINE | ID: covidwho-694565
ABSTRACT
Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Pneumonia, Viral
/
Protease Inhibitors
/
Virus Replication
/
Viral Nonstructural Proteins
/
Coronavirus Infections
/
Middle East Respiratory Syndrome Coronavirus
/
Betacoronavirus
Type of study:
Prognostic study
Language:
English
Journal subject:
Science
/
Medicine
Year:
2020
Document Type:
Article
Affiliation country:
Scitranslmed.abc5332
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