Furin Project idea

Initial Idea - screen for Furin inhibitors

they are required for protein S processing; large small molecule screens were not performed yet.

Reasons to go for Furin

The Pöhlmann published TMPRSS2 as the protease (Hoffman Pöhlmann 2020 Cell - pmid: 32142651). camostat mesylate requires 10-100microM for efficacy (actually very bad for cell culture); requires additional CatB/L for efficiency. This was all already known!!. There was even a better drug described nafamostat (10 times better!! - why did they not test it?)

Problems with TPMRSS2

No structure for TMPRSS2

No binding affinity and characterisation for the serine protease inhibitor camostat with TMPRSS2

No specificity characterisation for serine protease inhibitor Camostat: - we should check if Camostat also inhibits furin.

A screen for TMPRSS2 inhibitors would be also great - but structures missing.

For details: TMPRSS2 - S protein processing

Why should we still go for Furin: S protein of CoV-2 has acquired a Furin site in contrast to SARS S. This one seems to be functional. Furin - S protein processing

Structures available (bound and non-bound) Furin Structures

Easy assays available Furin - molbio methods

Important in many diseases Furin Protease

For Details: Furin - S protein processing

Furin enzyme can be purchased (NEB). I am getting expression clones from different labs.

Groups to participate

schubert@2bind.com

plach@2bind.de

haupt@pharm.ai

kaiser@pharm.ai

ralf.wagner@klinik.uni-regensburg.de

gernot.laengst@vkl.uni-regensburg.de

Take home

I think we should still give it a try.

Question I have to you and the overview to the project: Projektplanung und Tools

best start with SARS-CoV-2 Project idea