Coronavirus: Entry and Infection from an Interdisciplinary View 

Coronavirus (CoV) represents a serious public health concern because it infects a wide range of animals and has no readily available countermeasures when it emerges in humans and causes serious disease. Notable outbreaks in the human population are severe acute respiratory syndrome (SARS)-CoV (2002-2003), Middle East respiratory syndrome (MERS)-CoV (2012-present), and most recently, SARS-CoV-2/COVID-19, which has highlighted just how underprepared we are as a society to deal with these emerging viruses. There are two main ways to impede infection: 1) vaccinate to condition the immune system to recognize the virus, and 2) use antiviral strategies to interrupt some aspect of the infection process. For the first one, development of a vaccine takes more than 18 months and is not appropriate for rapid response to an emerging pandemic; furthermore, virus evolution requires continual boosting of immune system with updated formulations.

The second strategy can potentially respond more quickly because there are many places to interrupt the virus infection process. However this requires a more extensive knowledge of the biological processes the virus uses to gain entry into the host cell. In this presentation, I will cover the basics of enveloped virus entry, with a focus on virus life cycle. Then, I will focus in on the aspects of CoV biology and life cycle that make it both unique and rich with opportunities to exploit for antiviral development. In particular, I will focus on our recent work on the impact of calcium ions on CoV entry and the exploration of calcium-blocking drugs to reduce infection. Next, I will highlight recent work on antibody development against the membrane fusion machinery the virus uses to deliver its genome into the host cell. I will highlight approaches and knowledge gained across a wide variety of disciplines that have been necessary to help us understand this virus, and will continue to be integral to solving the challenges we currently face with it and viruses yet to emerge.