SARS-CoV-2 and therapeutic approaches
We are investigating what effect genetic variants of host genes which express products that facilitate SARS-CoV-2 infection have on the risk of developing the disease and its severity. We are also endeavouring to create the basis for innovative treatments by identifying substances that prevent the virus binding to human cells.
Clinically, COVID-19 manifests in many different ways, ranging from very mild or flu-like symptoms to pneumonia, acute respiratory distress syndrome and death. We argue that genetic variants of certain human SARS-CoV-2 host genes in the cells of affected organs such as the lungs, gastrointestinal tract and kidneys have a significant effect on clinical outcome alongside risk factors such as age, diabetes and high blood pressure.
Our project will investigate variants of different host genes, including angiotensin-converting enzyme 2 (ACE2), the host receptor for SARS-CoV-2. We will use various biochemical approaches to test the effects of such genetic variants on predisposition to SARS-CoV-2 infection. This will enable us to determine the binding affinity of SARS-CoV-2’s receptor binding domain for ACE2, and the pseudovirus entry assay will allow us to uncover the role of genetic predisposition to SARS-CoV-2 infection on the basis of the variability of certain human host genes. We will also be conducting small molecule compound screening in a bid to inhibit or block SARS-CoV-2 binding.
Expected results and envisaged products
The understanding of the biochemical effects of genetic variants of the coronavirus host gene that we gain will be progressively correlated with clinical data from large COVID-19 patient cohorts in a bid to determine what effect such variations have on the severity of coronavirus disease. We hope that small molecule compound screening will allow us to create novel inhibitors of viral susceptibility.
Specific contribution to tackle the current pandemic
The data obtained by analysing genetic predisposition to SARS-CoV-2 infection will help develop risk-appropriate safety and treatment strategies based on individual genotypic variation. We also hope that compound screening will lay the foundations for the development of novel antiviral treatments, such as oral or nasal spray formulations of any antiviral agents we identify, which can then be used as an alternative to vaccination.
New insights into the COVID-19 pandemic: Genetic polymorphisms, role of SLC6 amino acid transporters, renal aspects and therapeutic perspectives