Viral proteins as targets for antibody therapeutics and molecular detection agents

Abstract

The most recent viral pandemic, COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has so far resulted in the deaths of 5 million people, is a solemn reminder of the immense burden and challenge viruses can place on the economy and healthcare system and emphasizes the importance of preparedness and surveillance for viral outbreaks. Many human viruses are enveloped with a lipid bilayer and enter host cells by fusing the viral envelope to host membranes. Viral glycoproteins are main components of a virus and play a critical role in the membrane fusion process. They are also in many cases the major antigenic determinants of a virus. Understanding the structures and functions of fusogenic viral glycoproteins enables strategies for countermeasures and surveillance. In this dissertation, I studied the glycoproteins of two highly pathogenic human viruses, Henipaviruses (HNVs) and SARS-CoV-2 and showed that we can use structural information about the glycoproteins of these viruses in two different but related applications. One application is to understand how monoclonal antibodies and antibody cocktails can inhibit a virus from entering and infecting cells (Chapter 2 & 3). The other application is to design molecules, in this case a DNA aptamer, that specifically recognize a viral glycoprotein and use them for detection of the virus (Chapter 4).