Functional Profiling of HKU9-M via Virtual Ligand Screening

Christen Jones

Having resulted in more than 3.92 million deaths globally, the emergence of a pandemic due to the outbreak of Covid-19 beginning in late 2019, has highlighted the dire need to learn more about the coronavirus family.1 Known to have a high mutation rate, this family of viruses can easily adapt to new hosts and environments which facilitates their ability to be transmitted across species.2   It is also believed to be the reason why symptoms of the infected can range from mild to lethal. Bats have been identified as the progenitor hosts of this family of viruses, thus the study of bat coronaviruses are thought to lend insight on how the virus has mutated over time and can shed light on how those mutations have influenced the variation in virulence that is observed. In 2007, a novel coronavirus known as HKU9 was identified and will be the focus of the work presented. Specifically, a homology model of a novel macrodomain within the “SARS Unique Domain” of the nsp3 protein expressed by HKU9 will be used in virtual ligand screening in order to identify potential binding partners. This is important in that protein interactions tend to be specific. Thus, the identification of binding partners can offer insight into the role of the protein upon infection of the host. The results of this study may lend insight into the potential function of the protein and toward the development of therapies for coronaviral infections.