Teicoplanin Potently Blocks the Cell Entry of 2019-NCoV
Zhang, Junsong, et al. “Teicoplanin Potently Blocks the Cell Entry of 2019-NCoV.” BioRxiv, Cold Spring Harbor Laboratory, Feb. 2020, www.biorxiv.org, doi:10.1101/2020.02.05.935387.
Review written by:
Marta Gascon Parramon, edited by Robert Parry
Yellow - This article is a preprint and has not been certified by peer review. The authors describe a potential drug and confirm a mechanism of action. They test the drug in preliminary in vitro stages.
There is an urgent global need to develop drugs and vaccines for SARS-CoV2. Viral entrance into the cell is the first step of the life cycle and thus an ideal target. Teicoplanin, a glycopeptide antibiotic, has previously been shown to inhibit cellular entry of similar viruses (SARS-CoV and MERS-CoV) by inhibiting host-protease cathepsin L.
SARS-CoV2 enters cells using receptor mediated endocytosis. The spike glycoprotein (S protein) of SARS-CoV-2 mediates entry into cells by binding to ACE2 receptors. It is hypothesized that cell surface proteases (TMPRSS2) and lysosomal proteases (cathepsins) cleave and activate the S protein to fuse the virus to the cell membrane to then release the viral genome into the cytoplasm.
Teicoplanin is a semisynthetic glycopeptide antibiotic, typically reserved for serious infections caused by multidrug-resistant organisms (same drug class as vancomycin and has a similar spectrum of activity). In 2016, the authors studied teicoplanin along with its derivative lipoglycopeptides, dalbavancin, oritavancin, and telavancin, in cell culture experiments and found they inhibited Ebola virus, SARS-CoV, and MERS-CoV from entering cells. The current study looked at the effects of teicoplanin, dalbavancin, and vancomycin with SARS-CoV2. They did not conduct experiments with the other homologs but indicated that they might be considered for prophylaxis and treatment of SARS-CoV-2 potentially due to the findings in their 2016 study.
Cathepsin L was demonstrated to be necessary for 2019-nCoV cell entry in A549 cells. Because the Cathepsin L sequence is conserved between SARS-CoV and SARS-CoV-2, the authors hypothesized that teicoplanin could also inhibit the entry of SARS-CoV-2. They confirmed teicoplanin and its derivative dalbavancin effectively inhibited SARS-CoV-2 entry in A549 cells, with teicoplanin’s IC50 of 1.66 𝝻M. They extended these drugs inhibition of viral entry in HEK293T and Huh7 cell lines. Teicoplanin and dalbavancin were shown to limit entry of SARS-CoV2 into cells, but vancomycin did not.
Teicoplanin has low toxicity, minimal side effects, long half-life in blood plasma, convenient administration, and high safety when used in combination with other antibiotics. This article demonstrates that teicoplanin and dalbavancin might inhibit SARS-CoV2 entry into cells and have potential for use in prophylaxis and treatment.
-This article is a preprint and has not been certified by peer review.
-Teicoplanin and its homologs have not been tested in “in vivo” assays. t present it does not appear that any of these drugs have been chosen for clinical trials or given to patients for treatment. Investigators should be cautious when considering use of these medications, as these drugs are important for treating serious infections caused by multidrug-resistant organisms.
-Teicoplanin is not a commonly used antibiotic and thus may be difficult to produce large enough quantities for treatments of large populations. Teicoplanin is not approved by the FDA for use in the United States; it is utilized in other parts of the world (Asia, Europe, South America).