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

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.