2. Anti-infection Immunology/Inflammation
  3. SARS-CoV Virus Protease Interleukin Related
  4. WEHI-P8

WEHI-P8 is an orally active SARS-CoV-2 papain-like protease (PLpro) inhibitor with an IC50 of 12 nM and a Kd of 9.0 nM. WEHI-P8 reduces viral load, body weight loss, pulmonary inflammation, immune cell infiltration and pro-inflammatory mediator levels in SARS-CoV-2-infected mice. WEHI-P8 prevents pulmonary hemorrhage, immune cell infiltration, fibrotic remodeling and neuroinflammation, and improves cognitive function in a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC). WEHI-P8 is applicable for the research of COVID-19 and PASC.

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WEHI-P8

WEHI-P8 Chemical Structure

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WEHI-P8 Related Antibodies

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Description

WEHI-P8 is an orally active SARS-CoV-2 papain-like protease (PLpro) inhibitor with an IC50 of 12 nM and a Kd of 9.0 nM. WEHI-P8 reduces viral load, body weight loss, pulmonary inflammation, immune cell infiltration and pro-inflammatory mediator levels in SARS-CoV-2-infected mice. WEHI-P8 prevents pulmonary hemorrhage, immune cell infiltration, fibrotic remodeling and neuroinflammation, and improves cognitive function in a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC). WEHI-P8 is applicable for the research of COVID-19 and PASC[1].

In Vitro

WEHI-P8 (16-24 h) inhibits the activity of SARS-CoV-2 PLpro in FRET assays using HEK293T cells, with an EC50 of 298 nM[1].
WEHI-P8 (0-5 μM) inhibits SARS-CoV-2 replication in Vero cells in plaque assays, with an antiviral EC50 of 360 nM, which slightly decreases to 290 nM when combined with a P-glycoprotein inhibitor[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

WEHI-P8 Related Antibodies
Parmacokinetics
Species Dose Route T1/2 Cmax Tmax
Mice[1] 100 mg/kg p.o. 14 h 7.07 μM 1 h
In Vivo

WEHI-P8 (100-150 mg/kg; p.o.; administered at 6 h, 24 h, and 48 h post-infection) reduces SARS-CoV-2 viral load, prevents body weight loss, alleviates pulmonary pathological damage, and inhibits proinflammatory immune responses in a mouse model of acute severe COVID-19[1].
WEHI-P8 (150 mg/kg; p.o.; administered 2 h before infection, 6 h after infection, and 24 h after infection) prevents acute infection-induced mortality, alleviates long-term pulmonary pathological damage, mitigates neuroinflammation, and improves cognitive function in a PASC mouse model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6 J (WT, 6-8 weeks old, both sexes, intranasal infection with mouse-adapted SARS-CoV-2 P21 strain)[1]
Dosage: 100 mg/kg; 150 mg/kg
Administration: p.o.; 6 h, 24 h, 48 h post-infection
Result: Reduced lung viral burden.
Prevented infection-induced weight loss.
Reduced lung haemorrhage and inflammation to mild levels (100 mg/kg) or minimal/unremarkable levels (150 mg/kg).
Significantly reduced lung macrophage and neutrophil counts (100 mg/kg); significantly reduced lung macrophage, neutrophil, and T cell counts (150 mg/kg).
Significantly reduced lung levels of multiple pro-inflammatory cytokines/chemokines including IFN-γ, IL-1β, TNF, IL-18, IL-6, GROα, and MCP-1.
Reduced lung viral burden to levels below the lower limit of detection (150 mg/kg).
Animal Model: C57BL/6 J (WT, 11-12 weeks old, both sexes, intranasal infection with mouse-adapted SARS-CoV-2 P21 strain)[1]
Dosage: 150 mg/kg
Administration: p.o.; 2 h pre-infection, 6 h post-infection, 24 h post-infection
Result: Ensured 100% survival of treated mice during the acute infection phase, compared to vehicle-treated mice requiring euthanasia.
Prevented infection-induced weight loss during the acute phase.
Reduced lung haemorrhage and inflammatory foci to near-unremarkable levels, with lungs histologically similar to mock-infected mice.
Significantly reduced microglial activation (increased microglial projection area) in the hippocampus, indicating reduced neuroinflammation.
Significantly increased time spent exploring a novel object in the Novel Object Recognition Test, indicating improved cognitive function compared to vehicle and PLT-treated mice.
Rescued the infection-induced reduction in total distance travelled during behavioural testing in female mice, a deficit not mitigated by PLT treatment.
Molecular Weight

410.55

Formula

C25H34N2O3
SMILES

CCO/N=C([C@@H]1CCCN(C1)[C@H]2CC[C@H](CC2)O)/C3=CC4=C(C=C(C=C4)OC)C=C3
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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WEHI-P8 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

WEHI-P8SARS-CoVVirus ProteaseInterleukin RelatedSARS coronavirusILPLproSARS-CoV-2Vero cellsSARS-CoV-2 papain-like proteaseHEK293T cellspost-acute sequelae of COVID-19micehERG proteinCOVID-19PASC mouse modelsInhibitorinhibitorinhibit

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