Chemistry:EVG7
EVG7 is an experimental semisynthetic glycopeptide antibiotic developed at Leiden University by the research group of Nathaniel Martin, professor of Biological Chemistry at the Institute of Biology Leiden (IBL).[1] It is a chemically modified derivative of vancomycin that has been reported to be 100 to 10,000 times more potent than vancomycin against a range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).[1][2] The compound is named after PhD candidate Emma van Groesen (Emma Van Groesen), who synthesised it as the seventh analogue in a series of modified vancomycin compounds.[3]
As of 2026, EVG7 remains in preclinical development. Results from in vivo studies in mice have been published in Science Translational Medicine (2024) and Nature Communications (2025).[2][4]
Development
Development of EVG7 began around 2017, when Nathaniel Martin's group at Leiden University started exploring new chemical approaches to modify the structure of vancomycin.[1] Vancomycin is a naturally occurring glycopeptide antibiotic that has been used in hospitals for decades, but it carries a risk of kidney damage and faces growing problems with bacterial resistance.[1][5] PhD candidate Emma van Groesen synthesised around one hundred structural variants of vancomycin using a specific chemical modification strategy, out of which the seventh compound, designated EVG7, proved to be the most active.[3][5]
The project has been supported by two grants from the Dutch Research Council (NWO) NACTAR programme (Novel Antibacterial Compounds and Therapies Antagonising Resistance), a joint initiative with the Dutch Ministry of Health, Welfare and Sport aimed at bringing new antibiotics into (pre-)clinical testing.[6][7] Preclinical pharmacology studies are being conducted in collaboration with Coen van Hasselt of the Leiden Academic Centre for Drug Research (LACDR).[3]
Chemistry and mechanism of action
EVG7 belongs to a new class of semisynthetic antibiotics termed guanidino lipoglycopeptides. These are vancomycin derivatives bearing a positively charged guanidino moiety attached to a lipid group.[2] According to the original Science Translational Medicine study, the introduction of a lipidated guanidino group increases the compound's positive charge at physiological pH, which enhances its interaction with the bacterial cell surface.[2][8]
Like vancomycin, EVG7 inhibits bacterial cell wall synthesis by binding to lipid II, a key peptidoglycan precursor. However, EVG7 has been shown to bind lipid II with higher affinity than vancomycin, including the modified D-Ala-D-Lac variant of lipid II that is associated with vancomycin resistance.[2] This dual binding capability is thought to explain why EVG7 retains potent activity against vancomycin-resistant bacterial strains.[3][2]
Preclinical studies reported that EVG7 showed minimal toxicity toward eukaryotic cells and a low propensity for resistance selection in vitro.[2] In a mouse model of Staphylococcus aureus thigh infection and a 7-day sepsis survival study, EVG7 demonstrated superior efficacy compared to vancomycin, with minimal to mild kidney effects even at supratherapeutic doses.[2]
Activity against Clostridioides difficile
In October 2025, a study published in Nature Communications reported that EVG7 is effective against Clostridioides difficile infection (CDI) and can prevent its recurrence in a mouse model.[4] C. difficile is a Gram-positive anaerobic pathogen and the leading cause of healthcare-associated and antibiotic-associated diarrhea.[4]
In vitro susceptibility testing showed that clinical C. difficile isolates were up to 16 times more sensitive to EVG7 (MIC = 0.063-0.25 mg/L) compared to vancomycin (MIC = 0.5–2 mg/L).[4] In the mouse model, a low oral dose of EVG7 effectively treated primary CDI and prevented recurrence, outperforming a tenfold higher dose of vancomycin.[4][9]
Microbiome analysis revealed that EVG7-treated mice retained significantly more beneficial gut bacteria, particularly members of the Lachnospiraceae family, which are associated with colonization resistance against C. difficile.[4][9] By contrast, vancomycin treatment tended to eliminate large portions of the gut microbiome, including these protective commensal organisms, contributing to the high relapse rates seen with standard therapy.[9] The researchers noted that this selectivity may explain why even a low dose of EVG7 produced a lasting curative effect with no indication of relapse.[10]
Clinical outlook
As of early 2026, EVG7 has not yet been tested in humans.[11] The research team has indicated that toxicity studies must be completed before clinical trials can begin, which could take several years.[9][11] The initial clinical indication being considered for EVG7 is acute bacterial skin and skin structure infections (ABSSSIs), which is a common first target for new antibiotics, with subsequent evaluation for C. difficile and other infections envisioned if the drug gains regulatory approval.[10]
Leiden University has applied for a patent covering the use of EVG7 for the treatment of infections.[12] The developers have noted that securing investment for antibiotic development is a challenge, as pharmaceutical companies generally earn less revenue from antibiotics than from other therapeutic areas.[9][11]
See also
References
- ↑ 1.0 1.1 1.2 1.3 "Powerful new Leiden 'super antibiotic' may overcome resistance". 9 August 2024. https://www.universiteitleiden.nl/en/news/2024/08/prestigious-medical-journal-publishes-study-on-leiden-super-antibiotic.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Semisynthetic guanidino lipoglycopeptides with potent in vitro and in vivo antibacterial activity". Science Translational Medicine 16 (759). August 2024. doi:10.1126/scitranslmed.abo4736. PMID 39110780. https://research.rug.nl/en/publications/66dded93-d29d-42cd-947a-64947ead937e.
- ↑ 3.0 3.1 3.2 3.3 "Improving nature's antibiotic". January 2024. https://www.universiteitleiden.nl/en/news/2024/01/improving-natures-antibiotic.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 "Experimental glycopeptide antibiotic EVG7 prevents recurrent Clostridioides difficile infection by sparing members of the Lachnospiraceae family". Nature Communications 16 (1). October 2025. doi:10.1038/s41467-025-64067-w. PMID 41073374.
- ↑ 5.0 5.1 "Powerful New Antibiotic May Help Overcome Resistance". 9 August 2024. https://www.technologynetworks.com/drug-discovery/news/powerful-new-antibiotic-may-help-overcome-resistance-389644.
- ↑ "Four research projects into new antibiotics to start". https://www.nwo.nl/en/news/four-research-projects-into-new-antibiotics-to-start.
- ↑ "VALIANT - VALIdation of a Novel Glycopeptide ANTibiotic with Best-in-Class Potential". https://www.nwo.nl/en/projects/20813.
- ↑ "New 'super antibiotic' overcomes resistance". September 2024. https://www.sciencelink.net/news/new-super-antibiotic-overcomes-resistance/22192.article.
- ↑ 9.0 9.1 9.2 9.3 9.4 "Leiden 'super antibiotic' keeps dangerous gut bacterium under control with a low dose". October 2025. https://www.universiteitleiden.nl/en/news/2025/10/leiden-super-antibiotic-keeps-dangerous-gut-bacterium-under-control-with-a-low-dose.
- ↑ 10.0 10.1 "Super antibiotic EVG7 keeps beneficial bacteria intact". November 2025. https://www.sciencelink.net/news/super-antibiotic-evg7-keeps-beneficial-bacteria-intact/22985.article.
- ↑ 11.0 11.1 11.2 "New "super antibiotic" stops deadly gut infection without destroying the microbiome". 11 March 2026. https://www.sciencedaily.com/releases/2026/03/260311004824.htm.
- ↑ "Clever variant of antibiotic bypasses resistance in bacteria". October 2020. https://www.universiteitleiden.nl/en/news/2020/10/clever-variant-of-antibiotic-bypasses-resistance-in-bacteria.
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