Your browser doesn't support javascript.
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.
Li, Hui; Cheng, Chen; Shi, Shanshan; Wu, Yan; Gao, Yongfeng; Liu, Zhihao; Liu, Mingjian; Li, Zhaodong; Huo, Lijian; Pan, Xiaoyan; Liu, Shuwen; Song, Gaopeng.
  • Li H; Key Laboratory for Biobased Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou, 510642, China.
  • Cheng C; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • Shi S; Department of Microbiology and Immunology, College of Basic Medicine and Public Hygiene, Jinan University, Guangzhou, 510632, China.
  • Wu Y; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Gao Y; Key Laboratory for Biobased Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou, 510642, China.
  • Liu Z; Key Laboratory for Biobased Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou, 510642, China.
  • Liu M; Key Laboratory for Biobased Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou, 510642, China.
  • Li Z; Key Laboratory for Biobased Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou, 510642, China.
  • Huo L; Key Laboratory for Biobased Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou, 510642, China.
  • Pan X; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China. Electronic address: panxy@wh.iov.cn.
  • Liu S; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, 510515, China. El
  • Song G; Key Laboratory for Biobased Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou, 510642, China. Electronic address: songgp1021@scau.edu.cn.
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.
Subject(s)
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

Similar

MEDLINE

...
LILACS

LIS


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