Bigger Picture Talks at CEB with Professor Susan Daniel: Regulation of the coronavirus fusion peptide interaction with the host membrane and its impact on viral infectivity

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• Professor Susan Daniel, Cornell University
• Wednesday 20 April 2022, 16:00-17:00
• Department of Chemical Engineering and Biotechnology, West Cambridge Site, LT1; and online.

If you have a question about this talk, please contact Professor Tim Korter.

Our departmental seminar series, Bigger Picture Talks, runs throughout the academic year, inviting thought-leaders from across the world driving significant advances in our impact areas of energy, health and sustainability to share and discuss their work with us. This is a fantastic opportunity for us to hear from other leading researchers, develop new connections and collaborations, and discuss some of the wider questions in our field. We hope they will inspire new ideas for us all to take into our own research.

We are running this event in a hybrid format. To register to attend in person, please register through Eventbrite

To register to attend online, please register via our Zoom webinar registration page

Professor Susan Daniel, Fred H. Rhodes Professor at Cornell University presents her work exploring the replication cycle of the SARS -CoV-2 virus.

Abstract

The coronavirus disease 2019 (COVID-19) necessitates develop of effective therapies against the causative agent, SARS -CoV-2, and other pathogenic coronaviruses (CoV) that have yet to emerge. Focusing on the CoV replication cycle, specifically the entry steps involving membrane fusion, is an astute choice because of the conservation of the fusion machinery and mechanism across the CoV family. For coronavirus, entry into a host cell is mediated by a single glycoprotein protruding from its membrane envelope, called spike (S). Within S, the region that directly interacts with the membrane is called the fusion peptide, FP. It is the physico-chemical interactions of the FP with the host membrane that anchors it, enabling the necessary deformations of the membrane leading to delivery of the viral genome into the cell when a fusion pore opens. Thermodynamic, kinetic, and intermolecular interactions are useful to understand molecular level FP interactions with the host membrane. This knowledge can be leveraged to stop the spread of infection. Here, we examine the impact of calcium ions on CoV entry. Using cell infectivity, biophysical assays, and spectroscopic methods, we found that calcium ions stabilize the FP structure during conformational change that then allows its insertion into the host membrane, resulting in increased lipid ordering in the membrane. This lipid ordering precedes membrane fusion and correlates with increased fusion activity and higher levels of infection when calcium in present. As such, depletion of calcium ions leads to structure and activity changes in the fusion peptide that correlate well with in vitro experiments using calcium-chelating agents to block cell infection. In a final set of experiments, we show calcium channel blockers can block virus infection in lung cells.

This talk is part of the Chemical Engineering and Biotechnology Departmental Seminars series.

This talk is included in these lists:

• All Talks (aka the CURE list)
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• Cambridge talks
• Chemical Engineering and Biotechnology
• Chemical Engineering and Biotechnology Departmental Seminars
• Department of Chemical Engineering and Biotechnology, West Cambridge Site, LT1; and online
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• ME Seminar
• School of Technology
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