SARS-CoV-2 Protease Assays for Testing of new COVID-19 Therapeutics
In today’s global COVID-19 pandemic crisis, protease studies are more important than ever, since they are essential for virus infections. Existing protease inhibitors are now being added to clinical trials for COVID-19, and more specific proteases have been under special investigation as new strategical targets to prevent and cure COVID-19 infections. These targets include ACE2, TMPRSS2 (Transmembrane protease serine 2) that aid the virus entry into host cells, and Main Protease (Mpro) that is indispensable for virus replication and infection process.
To support the drug discovery community in the challenge to identify efficacious COVID-19 drugs, we have developed specific assays targeting proteases that are essential for SARS-CoV-2 virus entry and replication.
- Fluorescence-based activity assays
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Low and large scale screening, as well as high-throughput screening options, are available
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Full protease panel screening is available for off-target analysis.
Proteases as Targets against SARS-CoV-2
Host proteases furin and TMPRSS2 play a vital role in the pathogenesis and replication of SARS-CoV-2 by cleaving the spike protein to enable membrane fusion for virus entry. Cathepsin L further primes the spike protein in the acidic environment of endosomes. PLpro and Mpro are viral proteases required for virus replication. They proteolytically process the polyprotein, which is a prerequisite for virus assembly. PLpro is also known to interfere with the anti-viral immune response of the host cell.
List of Targets
| Target | Synonyms | Data |
|---|---|---|
| Cathepsin L | CTSL, CTSL1 | Data sheet |
| Furin | FUR, PACE, PCSK3 | Data sheet |
| Mpro | 3CLpro | Data sheet |
| PLpro | NSP3, Papain-Like cysteine protease | Data sheet |
| TMPRSS2 | Transmembrane protease serine 2, PRSS10 | Data sheet |
| TMPRSS6 | Transmembrane protease serine 6, matriptase 2 | Data sheet |
| ACE2 | angiotensin I converting enzyme 2 | Please inquire |
| Cathepsin B | APP secretase, Cathepsin B1, CATB, CTSB, CPSB | Data sheet |
Assay Details
The papain-like protease (PLpro) is responsible for cleavage of the coronavirus polyprotein necessary for virus assembly. PLpro also suppresses the host innate immune through the reversal of ubiquitination and ISGylation events. We offer the investigation of the proteolytic activity of PLpro for deubiquitination and for proteolysis of a peptide.
The PLpro assay allows for screening compounds using a fluorogenic substrate, either Z-RLRGG-AMC or Ubiquitin-AMC. PLpro cleaves the substrate for the release of AMC and the resulting fluorescence can be quantified with a luminometer for readout of PLpro enzymatic activity.
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