A New Therapeutic and Diagnostic Target for SARS-CoV-2 and COVID-19
The seriousness of the COVID-19 pandemic is largely in part due to its novelty; our understanding of its pathology is still developing, and our lack of knowledge contributes to our inability to effectively treat it. An understanding of the viral mechanism of action is critical to developing treatments for it. It is thought that SARS-CoV-2 gains entry to cells using a pathway that relies upon lysosomal acidification for entry, but the crucial molecules that regulate such lysosomal activity have not been defined; further, it may be that functional genetic variants in molecules could confer either cellular protection or susceptibility, as indicated by the wide and unexplained variation of disease severity in the global population. Identification of these molecules could serve as a crucial foundation for development of novel therapeutic drugs and genotypic risk assessment, expediting global recovery from this devastating pandemic.
Description
Prior research in a University of Pittsburgh laboratory had focused on investigating the pathobiology of endothelial cell nuclear receptor coactivator 7 (NCOA7). NCOA7 has been shown to regulate immunoactivation of the endothelium and subsequent leukocyte adhesion, leading to presumable viral infiltration. NCOA7 accomplishes this by altering lysosomal acidification, a process that has been independently found to affect entry of other enveloped viruses such as the similarly-structured influenza virus. Researchers have also identified an allele-specific mechanism that may influence NCOA7 expression and cellular susceptibility to infection. This invention includes the development of small molecules, gene therapy systems, RNAi-based systems, or the use of certain inhibitors to control NCOA7 expression to prevent or improve infection in addition to the use of NCOA7 SNP genotyping as a means of individual risk of infection and disease severity in order to prevent infection or complications. NCOA7 may prove to be immediately relevant for development of new drugs and repurposing of old drugs for therapies for this new pandemic.Applications
· Platform for developing drugs to prevent or improve infection and downstream disease from SARS-CoV-2/COVID-19· Repurposing of old drugs
· Public health initiatives to identify persons at high and low risk of infection and severity of disease
· Development of gene editing platforms to prevent infection or disease complications in vulnerable populations
Advantages
· No prior initiatives have explored the therapeutic or diagnostic benefit of modulating NCOA7 or its functional SNP· Enables genotype-based assessment of risk in order to protect vulnerable populations from infection or disease complications, in addition to predicting disease severity and progression to proactively treat and triage patients
· Prevents cellular entry by SARS-CoV-2