We have developed β-lactam peptidomimetic inhibitors of flaviviral proteases with a molecular weight between 340 and 500 that are active in a cellular assay in the single-digit micromolar range, combined with low cytotoxicity and low off-target interference. A key structural element of the compound class is the inclusion of a β-lactam moiety in the structural backbone.
The β-lactam ring facilitates a large variation of substituents as well as 3D organization of the pharmacophore. Therefore, we are confident that this strategy opens a route to inhibitors of other proteases, such as the SARS-CoV-2 protease or TMPRSS2 that are crucial for entry and replication of SARS-CoV-2.
Addressing target audiences and expressing needs
- Grants and Subsidies
We are looking for projects and investors who would be interested in supporting and investing in the development of the β-lactam inhibitors of various proteases. The main interest and focus at this time would be on the coronavirus proteases to address the current and potentially future threats by coronaviruses.
- Public or private funding institutions
- Research and Technology Organisations
R&D, Technology and Innovation aspects
We synthesize diversely substituted β-lactams in a stereoselective fashion. We further couple them to various moieties, making the β-lactam either a central or terminal motif of a compound. The compounds are tested in a biochemical and cellular model. We have at our disposal assays for the determination of the activity against viral proteases, including the flavivirus and coronavirus protease.
