Identification of inhibitors for the S1-ACE2 interaction of the SARS-CoV-2 using magnetically modulated biosensors

Shira Roth; Amos Danielli; Michael Margulis

doi:10.1117/12.2610236

4 March 2022 Identification of inhibitors for the S1-ACE2 interaction of the SARS-CoV-2 using magnetically modulated biosensors

Shira Roth, Amos Danielli, Michael Margulis

Author Affiliations +

Proceedings Volume 11979, Frontiers in Biological Detection: From Nanosensors to Systems XIV; 1197906 (2022) https://doi.org/10.1117/12.2610236
Event: SPIE BiOS, 2022, San Francisco, California, United States

Abstract

The outbreak of the coronavirus disease emphasized the need for fast and sensitive inhibitor screening tools for the identification of new drug candidates. In SARS-CoV-2, one of the initial steps in the infection cycle is the adherence of the receptor-binding domain (RBD) of the spike protein 1 (S1) to the host cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, inhibition of S1-ACE2 interaction may block the entry of the virus to the host cell, and thus may limit the spread of the virus in the body. We demonstrate a rapid and quantitative method for the detection and classification of different types of molecules as inhibitors or non-inhibitors of the S1-ACE2 interaction using magnetically modulated biosensors (MMB). In the MMB-based assay, magnetic beads are attached to the S1 protein and the ACE2 receptor is fluorescently labeled. Thus, only when the proteins interact, the fluorescent molecule is connected to the magnetic bead. To increase the sensitivity of fluorescence detection, the complex of magnetic beads and attached fluorescent molecules are aggregated by two opposing electromagnets and are moved from side to side in a periodic motion in and out of a laser beam, emitting a flashing signal that is collected by a digital camera. When an inhibitor interferes with the interaction, the signal is reduced. The MMB-based assay is much faster and has minimal non-specific binding than the commonly used ELISA. It can be adjusted to other interactions, and therefore can be utilized as a global tool for inhibitor screening.

Conference Presentation

Citation Download Citation

Shira Roth, Amos Danielli, and Michael Margulis "Identification of inhibitors for the S1-ACE2 interaction of the SARS-CoV-2 using magnetically modulated biosensors", Proc. SPIE 11979, Frontiers in Biological Detection: From Nanosensors to Systems XIV, 1197906 (4 March 2022); https://doi.org/10.1117/12.2610236

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