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Targeting the ADPR-binding macrodomain associated deMARylation/dePARylation enzyme activity as novel approach towards SARS-CoV-2 (A18)

Subject Area Biochemistry
Term since 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 335447717
 
As part of non-structural protein 3 (nsp3) SARS-CoV-2 harbours an ADPR-binding macrodomain with deADP-ribosylating activity that contributes to the suppression of the antiviral interferon response of the host. Aim of the project is to develop a structure-activity relationship for the viral macrodomain using ADPR analogues and to identify non-nucleotide inhibitors using a virtual screening approach. In addition we will analyse the role of the macrodomain in infection experiments using a reverse genetics approach and determine the effect of naturally occurring mutations in the macrodomain of nsp3 on enzymatic activity and viral replication.
DFG Programme Collaborative Research Centres
Applicant Institution Universität Hamburg
 
 

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