In the past 25 years, human-infective coronaviruses (hCoVs) have been responsible for two epidemics (SARS-CoV and MERS-CoV) as well as the COVID-19 pandemic (SARS-CoV-2), highlighting coronaviruses as critically important human pathogens. Aside from these highly pathogenic coronaviruses, there are four endemic human coronaviruses: HCoV-229E, HCoV-NL63, HCoV-HKU1 and HCoV-OC43 which account for approximately 30% of common colds globally. These typically cause mild symptoms, and in rare cases result in mortality in vulnerable populations. Studying these endemic coronaviruses offer insights that help us better understand and respond to future coronavirus threats.
During my PhD, I investigated potential therapeutics against HKU1. I generated panels of nanobodies against two key proteins which mediate HKU1 infection: the receptor binding domain of HKU1 as well as its host receptor TMPRSS2. By employing a panel of biophysical and function assays including biolayer interferometry, FRET assay, pseudovirus neutralisation and X-ray crystallography, I have identified nanobodies which neutralise HKU1infection by either targeting the virus or the host receptor. My work looks to improve our preparedness for future emerging pathogenic coronaviruses by deepening our understanding of a previously understudied endemic coronavirus.