Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity

Pharmaceuticals

Annelies Stevaert¹  Gyula Batta¹  Pál Herczegh²  Anikó Borbás³  Zsolt Szűcs⁴  Lieve Naesens⁵  Eszter Ostorházi⁵ 

[1] Belgium;Department of Medical Microbiology, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary;Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary;Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary;Rega Institute for Medical Research, KU Leuven, B-3000 Leuven;

关键词: glycopeptide antibiotic;    vancomycin aglycone hexapeptide;    antiviral;    influenza virus;    human coronavirus;   

DOI  :  10.3390/ph13070139

来源: DOAJ

【 摘 要 】

Influenza A and B viruses are a global threat to human health and increasing resistance to the existing antiviral drugs necessitates new concepts to expand the therapeutic options. Glycopeptide derivatives have emerged as a promising new class of antiviral agents. To avoid potential antibiotic resistance, these antiviral glycopeptides are preferably devoid of antibiotic activity. We prepared six vancomycin aglycone hexapeptide derivatives with the aim of obtaining compounds having anti-influenza virus but no antibacterial activity. Two of them exerted strong and selective inhibition of influenza A and B virus replication, while antibacterial activity was successfully eliminated by removing the critical N-terminal moiety. In addition, these two molecules offered protection against several other viruses, such as herpes simplex virus, yellow fever virus, Zika virus, and human coronavirus, classifying these glycopeptides as broad antiviral molecules with a favorable therapeutic index.

【 授权许可】

Unknown