Ebola virus infection can cause severe hemorrhagic fever with a high mortality 
in humans. The outbreaks of Ebola viruses in 2014 represented the most serious 
Ebola epidemics in history and greatly threatened public health worldwide. The 
development of additional effective anti-Ebola therapeutic agents is therefore 
quite urgent. In this study, via high throughput screening of Food and Drug 
Administration-approved drugs, we identified that teicoplanin, a glycopeptide 
antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses 
into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on 
transcription- and replication-competent virus-like particles, with an IC50 as 
low as 330 nm Comparative analysis further demonstrated that teicoplanin is able 
to block the entry of Middle East respiratory syndrome (MERS) and severe acute 
respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin 
derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit 
the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that 
teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of 
cathepsin L, opening a novel avenue for the development of additional 
glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, 
given that teicoplanin has routinely been used in the clinic with low toxicity, 
our work provides a promising prospect for the prophylaxis and treatment of 
Ebola, MERS, and SARS virus infection.