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Point Of Care Technology For SARS-CoV-2 Detection and Neutralization

Interests: Antibody, Antibody
Published:
Lead Inventor: Anthony Kossiakoff
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SUMMARY

  • SARS-CoV-2’s enters cells when the receptor binding domain (RBD) of its spike protein (S-protein) interacts with angiotensin-converting enzyme 2 (ACE2).  In order to block this RBD-ACE2 interaction, clinicians need Point of Care (POC) assays to detect and neutralize the virus as early as possible. 

  • The faculty inventor has developed a modular POC viral detection assay with orders of magnitude greater signal-to-noise detection sensitivity and target specificity than ELISA tests. This same technology also shows potential as the basis for a new antiviral treatment for COVID-19.

  • The assay detects virus particles at low nM levels thanks to its split-enzyme β-lactamase (BL) fabs strategy.  Anti-RBD fabs are also powerful viral blockers (IC50-0.5 nM) of viral entry into cells.

  • In vitro proof of concept experiments demonstrate that this assay also detects full-length S-proteins at different concentrations (from 7 to 125 nM) using complementary parts (i.e. pGA1-BLF1/sRBD7 and BLF2-pGA1/RBD1).

 

FIGURE

A) SARS-CoV-2 detection. Two separate fragments of BL attach to two different fabs via protein pGA1-LRT interaction. BL fragments associate to form an active enzyme state when fabs bind to the receptor binding domain (RBD). 

B) SARS-CoV-2 neutralization. Anti-RBD fabs block interactions with human ACE2 receptors on the cell surface. Different concentrations of the RBD1 and RBD7 fabs prevent cell death. Neutralization IC50 value for RBD1 is 4.8 nM. Virus neutralization improved over 2.5-fold by RBD1 dimerization. IC50 neutralization for the dimerized RBD1 was 1.9 nM. IC50 of mRBD 1.15 was 10-fold improved with a value of 0.48 nM. Results were normalized. All experiments were done in triplicate and error bars represent SD value from the mean.
 

ADVANTAGES

ADVANTAGES

  •  Effective for detecting SARS-CoV-2, Ebola, and Zika.

  •  Fabs are potent inhibitors (IC50-0.5 nM) to viral entry into cells – a promising basis for new antiviral drugs.

  • This technology can be freeze-dried, packed, and delivered in a point-of-care kit – without losing sensitivity.

APPLICATIONS

  • Point-of-Care Diagnostics
  • Antiviral therapeutics

 

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