Vinyl Sulfone-Based Inhibitors of Nonstructural Protein 2 Block the Replication of Venezuelan Equine Encephalitis Virus.
| Autor: | Zhang H; Department of Chemistry, Physics, and Atmospheric Sciences, Jackson State University, Jackson, Mississippi 39217-0095, United States., Harmon M; Department of Chemistry, Physics, and Atmospheric Sciences, Jackson State University, Jackson, Mississippi 39217-0095, United States., Radoshitzky SR; The Geneva Foundation, Countermeasure Development Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland 21702-5011, United States., Soloveva V; Cherokee Nation Assurance, Countermeasure Development Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland 21702-5011, United States., Kane CD; Research Program Office, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland 21702-5011, United States., Duplantier AJ; Cherokee Nation Assurance, Countermeasure Development Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland 21702-5011, United States., Ogungbe IV; Department of Chemistry, Physics, and Atmospheric Sciences, Jackson State University, Jackson, Mississippi 39217-0095, United States. |
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| Jazyk: | angličtina |
| Zdroj: | ACS medicinal chemistry letters [ACS Med Chem Lett] 2020 Sep 02; Vol. 11 (11), pp. 2139-2145. Date of Electronic Publication: 2020 Sep 02 (Print Publication: 2020). |
| DOI: | 10.1021/acsmedchemlett.0c00215 |
| Abstrakt: | Emerging infectious diseases like those caused by arboviruses such as Venezuelan equine encephalitis virus (VEEV) pose a serious threat to public health systems. Development of medical countermeasures against emerging infectious diseases are of utmost importance. In this work, an acrylate and vinyl sulfone-based chemical series was investigated as promising starting scaffolds against VEEV and as inhibitors of the cysteine protease domain of VEEV's nonstructural protein 2 (nsP2). Primary screen and dose response studies were performed to evaluate the potency and cytotoxicity of the compounds. The results provide structural insights into a new class of potent nonpeptidic covalent inhibitors of nsP2 cysteine protease represented by compound 11 (VEEV TrD, EC Competing Interests: The authors declare no competing financial interest. |
| Databáze: | MEDLINE |
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