Identification, optimization, and biological evaluation of 3-O-ß-chacotriosyl ursolic acid derivatives as novel SARS-CoV-2 entry inhibitors by targeting the prefusion state of spike protein.
Eur J Med Chem
; 238: 114426, 2022 Aug 05.
Article
in English
| MEDLINE | ID: covidwho-1821218
ABSTRACT
The COVID-19 pandemic generates a global threat to public health and continuously emerging SARS-CoV-2 variants bring a great challenge to the development of both vaccines and antiviral agents. In this study, we identified UA-18 and its optimized analog UA-30 via the hit-to-lead strategy as novel SARS-CoV-2 fusion inhibitors. The lead compound UA-30 showed potent antiviral activity against infectious SARS-CoV-2 (wuhan-HU-1 variant) in Vero-E6 cells and was also effective against infection of diverse pseudotyped SARS-CoV-2 variants with mutations in the S protein including the Omicron and Delta variants. More importantly, UA-30 might target the cavity between S1 and S2 subunits to stabilize the prefusion state of the SARS-CoV-2 S protein, thus leading to interfering with virus-cell membrane fusion. This study offers a set of novel SARS-CoV-2 fusion inhibitors against SARS-CoV-2 and its variants based on the 3-O-ß-chacotriosyl UA skeleton.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Triterpenes
/
Virus Internalization
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19 Drug Treatment
Type of study:
Experimental Studies
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Journal:
Eur J Med Chem
Year:
2022
Document Type:
Article
Affiliation country:
J.ejmech.2022.114426
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