(27bx) Illuminating Cell Entry Pathways of Sars-Cov-2 By Replicating Distinct Host Environments on a Bioelectronic Sensor

Emerging viruses will continue to be a threat to human health and well-being in the foreseeable future. The COVID-19 pandemic revealed the necessity for rapid viral sensing and inhibitor screening in mitigating viral spread and impact, as well as the need to understand the entry process itself in order to design rational drug inhibitors. Reassembling cell membranes on functional supports can facilitate sensing and studying biorecognition events at the cell surface, such as the infection process of a virus. Here, we introduce a bioelectrical sensing platform on which biomimetic supported lipid bilayers (SLBs) are assembled and electrical signals are used to detect distinct SARS-CoV-2 virus entry pathways into a host cell. By recreating the specific host microenvironmental signals, we are able to monitor receptor binding and membrane fusion events between SLBs and spike-decorated virus pseudo particles (VPPs) via changes in membrane resistance and fluorescence using electrochemical impedance spectroscopy (EIS) and fluorescence microscopy, respectively. Of critical relevance here, we can consistently re-create the distinct chemical signaling of the host that drives either a plasma membrane or endosomal entry pathway observed in nature. Though SARS-CoV2 VPPs serve as a model system, we anticipate that the full capacity of this device can be realized by expanding to other enveloped viruses to quantifiably explore virus/host interactions, which can be tuned to mimic the membrane environment of a particular host. Such a platform that recapitulates the virus infection process of the host will be invaluable to the high throughput development of antiviral drugs.