Recreating the Biological Steps of Viral Infection on a Cell-Free Bioelectronic Platform to Profile Viral Variants of Concern

RNA viruses such as SARS-CoV-2 and influenza frequently mutate due to they lack of error-repair mechanisms while replicating the RNA genome. To assist speeding up the societal response over emerging viruses of concern, platforms that can study the infection pathway of a virus and rapidly determine its propensity for infection are needed. We have recently developed a cell-free bioelectronic platform based on supported lipid bilayers (SLBs) to recreate the entry pathways of SARS-CoV-2, and have accurately quantified the fusogenicities of different mutants by the electrical signals that matches with previous reports. Our results suggest the specific binding between Spike protein containing viral pesudoparticles and SLBs recapitulated with ACE2 receptors does not change membrane resistance, while the fusion events catalyzed by proteases such as cathepsin and TMRPSS2 increase membrane resistance significantly. Not limited to SARS-CoV-2, our system also shows promises in detecting the fusion between live measles viruses and cell-free expressed influenza viruses with SLBs, confirming the robustness and customizability of SLB-on-electrode platform in studying the early steps of viral entry into host cells.