Developing a Sex-specific Therapy for Viral Infections

The COVID-19 outbreak, caused by the SARS-CoV-2 virus, has shown high infection and mortality rates worldwide. Although most people experience mild symptoms, some develop a severe form of COVID-19 driven by a reactive “storm” of inflammation and cytokines leading to long-term damage to the lungs and multiple organs. Interestingly, males are more likely to develop the severe form of COVID-19, as males are twice more likely to require ICU admission and are 30% more likely to die due to COVID-19 compared to females. The male-bias in COVID-19 severity is consistent with other viral infections including the influenza A virus and Middle East Respiratory Syndrome virus, highlighting a common male-vulnerability to viral infections. While social and lifestyle factors such as smoking and hygiene are likely to contribute, converging evidence indicate that sex differences in immune response to viral infections significantly contribute to this male-bias. Our preliminary work suggests, Y-chromosome gene, SRY, may contribute to heightened immune response and consequently disease severity in males. In view of these promising results, we will now validate SRY as a novel male-specific target for viral infections by: i) assessing the relationship between SRY expression and disease severity, ii) testing whether SRY inhibiting molecules can reduce disease severity in a primary human cellular model of viral infection. To achieve this, we have drawn together a team with unique expertise in SRY (Dr Lee) and viral infections (A/Prof. Tate). Dr Lee’s and A/Prof. Tate’s team have well established protocols for SRY detection and SRY inhibition in human cell cultures, and human cellular models of viral infection, and assays for virus and cytokine detection.