Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2.
ChemMedChem
; 16(2): 340-354, 2021 01 19.
Article
in En
| MEDLINE
| ID: mdl-32930481
ABSTRACT
Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PLpro ) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS-CoV PLpro . Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PLpro are valuable starting points for the development of new pan-coronaviral inhibitors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Benzamides
/
Cysteine Proteinase Inhibitors
/
Isoindoles
/
Coronavirus 3C Proteases
/
SARS-CoV-2
Limits:
Animals
Language:
En
Journal:
ChemMedChem
Journal subject:
FARMACOLOGIA
/
QUIMICA
Year:
2021
Document type:
Article
Affiliation country: