Sub-Picomolar Detection of SARS-CoV-2 RBD via Computationally-Optimized Peptide Beacons

The novel coronavirus SARS-CoV-2 continues to pose a significant global health threat. Along with vaccines and targeted therapeutics, there is a critical need for rapid diagnostic solutions. In this work, we employ a deep learning-based protein design to engineer molecular beacons that function as conformational switches for high sensitivity detection of the SARS-CoV-2 spike protein receptor-binding domain (SRBD). The beacons contain two peptides, together forming a heterodimer, and a binding ligand between them to detect the presence of S-RBD. In the absence of S-RBD (OFF), the peptide beacons adopt a closed conformation that opens when bound to the S-RBD and produces a fluorescence signal (ON), utilizing a fluorophore-quencher pair at the two ends of the heterodimer stems. Two candidate beacons, C17LC21, and C21LC21 can detect the S-RBD with limits of detection (LoD) in the sub-picomolar range. We envision that these beacons can be easily integrated with on-chip optical sensors to construct a point-of-care diagnostic platform for SARS-CoV-2.

Name thesis:degree_name

Master

Department dc:contributor.department

Program in Media Arts and Sciences (Massachusetts Institute of Technology)

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2021

Author dc:creator

• Tripathy, Soumya Pratap

Advisor dc:contributor.advisor

• Jacobson, Joseph M.

Statement dc:rights

• In Copyright - Educational Use Permitted
• Copyright MIT

Licence dc:rights.uri

• http://rightsstatements.org/page/InC-EDU/1.0/

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/142839

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/142839