E.T. Chen, J.T. Thornton, S-H. Duh
Advanced Biomimetic Sensors, Inc.,
Keywords: superconducting current, native ACE2 memristive sensor, reversible membrane potential (RMP), nanostructure biomimetic ACE2 memristive sensor, inhibition of S1 attack ACE2, ratio of action potential/resting potential
Summary:Spike (S) protein of the SARS-CoV-2 virus attacks the human angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD), and entries into human cells. Speedy screen processing for chosen pharmaceutical candidates has been in high demand. and the processing aces challenges. We report a memristive electrochemical biomimetic ACE2 sensor, sensor 1, which was developed, for the purpose of speeding up the evaluations for a candidate S1 inhibitor, such as ABS02, and the results obtained to compare with an established S1 inhibitor Remdesivir. The ability of the two inhibitors to reduce the S1 protein bound with ACE2 was evaluated with a cyclic volumetric (CV) method against a native ACE2 sensor, as sensor 2; and the ability to restore the function of cell reversible membrane potential (RMP) was evaluated by a double step chronopotentiometry (DSCPO) method over S1 concentrations between 40 aM to 120 nM under antibody-free, tracer-free, and reagent-free conditions. Results from the CV method at a scan rate of 10 kHz showed ABS02 and remdesivir successfully blocked S1 attack ACE2 by 99.58% and 99.52% over S1 concentration range 40 aM-60 nM with r values < 0.38, and <0.15 using the biomimetic ACE2 sensor against S1 controls, respectively, which has a sensitivity -200 µA/nM and an r value -0.999 due to the two inhibitors’ presence induced superconducting current at zero-bias formed super positioning oscillation at 10KHz; While using the native ACE2 sensor, ABS02 and remdesivir had 99.5% and 91% blacked S1 attack ACE2 with r values 0.39, and 0.84 over S1 40 aM-120 nM, and 40 aM to 60 nM, respectively, against S1 controls with a sensitivity 6.0 µA/nM, and an r value 0.999 over S1 4 aM-120 nM. The results for validating the restoration of the RMP by the ratio of action potential vs. Resting potential used the biomimetic ACE2 sensor by the DSCPO method, ABS02 and remdesivir both (n=15 for each method) have ratio values 100% located in the safety zoon, but S1 (n=18) has more than 50% data located outside of the safety zoon, herein we conclude our new approaches may shine the light for speedy-up pharmaceutical candidate screening processing. Our prior works are: TechConnect Briefs 111, 2022; TechConnect Briefs, 271-274, 2017. An example issued patent: A nanostructured Biomimetic device for detecting a cancer cell or cancer cells, US 9,534,999, 2017. Our current accomplishments are:1) developed memristors using native ACE2 cross-linked polymers showed the capability to sense the presence of S1 biocommunication with ACE2, and a biomimetic ACE2 multiple layered nanostructured memristive sensor promoted 33-fold increase sensitivity compared with the native ACE2 sensor; 2). Data Showed ABS02 and remdesivir both have higher than 99.5% rate block S1 attack, and the 100% data in the safety zoon of RMP compared S1 alone only 50% data in the safe zoon. 3) Our approach helps speed up the candidates' toxin inhibitors development and screening, it shortened the time and reduce the budget, and save thousands of lives when the method is moved to clinical study.