Newswise — Scientists have employed infected heart and lung stem cells of COVID-19 to gain deeper insights into the disease's effects on various organs, thereby facilitating the development of more precise therapies.

The study, jointly conducted by Murdoch Children's Research Institute and the Peter Doherty Institute for Infection and Immunity (Doherty Institute), observed substantial variations in the reactions to SARS-CoV-2 based on cell types. This enabled the researchers to pinpoint efficacious antiviral medications for combating infections in heart and lung cells. The results were published in the Stem Cell Reports' commemorative 10th anniversary edition.

Associate Professor David Elliott from Murdoch Children's, who is also a principal investigator at The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), emphasized that uncovering the diverse cellular reactions in various organs due to COVID-19 would offer novel perspectives on treatment approaches.

He stated, "In order to advance our understanding of how SARS-CoV-2 affects various organs, we manipulated human stem cells within the laboratory to develop lung and heart cells, which were then intentionally infected with the virus.""Our findings revealed distinct antiviral and toxicity profiles in the heart and lungs, which could serve as valuable insights for the development of improved COVID-19 therapies and the management of associated complications."

"Our research underscores the significance of employing multiple cell types when assessing antiviral medications to identify optimal drug combinations for the effective treatment of viruses that impact multiple organ systems."

Professor Kanta Subbarao, a virologist and the Director of the WHO Collaborating Centre for Reference and Research on Influenza at the Doherty Institute, along with the Royal Melbourne Hospital and the University of Melbourne, highlighted that although the primary site of infection for SARS-CoV-2 is the respiratory tract, severe cases of COVID-19 can lead to complications in the lungs and heart.

Up to 78 percent of individuals who have recovered from COVID-19 exhibit cardiac complications, and approximately 60 percent of patients experience persistent myocardial inflammation.

Professor Subbarao emphasized that while COVID-19 vaccines have proven to be highly effective in preventing severe illness and fatalities, the treatment of COVID-19 necessitates the use of antiviral compounds, especially with the emergence of variant viruses that can evade immunity.

“To date, only a handful of drugs have been approved for use in hospitalised COVID-19 patients and more are needed.” 

In the study, various approved drugs for treating COVID-19, such as Remdesivir and Molnupiravir, were examined, and their effectiveness in treating infection in lung and heart stem cells was compared. The research identified Alectinib and SPHINX31 as promising antiviral agents for SARS-CoV-2 in both heart and lung cells.

Professor Subbarao expressed, "Through our study, we have offered valuable insights into the interactions between the virus and host tissues that are notably impacted in COVID-19. These findings have important implications for expanding therapeutic options in the fight against the disease."

The research findings were a result of collaborative efforts involving researchers from Monash University, The University of Sydney, The Walter and Eliza Hall Institute of Medical Research, the University of Melbourne, and The Royal Children's Hospital.

Publication: Rajeev Rudraraju, Matthew J. Gartner, Jessica A. Neil, Elizabeth S. Stout, Joseph Chen, Elise J. Needham, Michael See, Charley Mackenzie-Kludas, Leo Yi Yang Lee, Mingyang Wang, Hayley Pointer, Kathy Karavendzas, Dad Abu-Bonsrah, Damien Drew, Yu Bo Yang Sun, Jia Ping Tan, Guizhi Sun, Abbas Salavaty, Natalie Charitakis, Hieu T. Nim, Peter D Currie, Wai-Hong Tham, Enzo Porrello, Jose M. Polo, Sean J. Humphrey, Mirana Ramialison, David A. Elliott and Kanta Subbarao, ‘Parallel use of human stem cell lung and heart models provide insights for SARSCoV-2 treatment,’ Stem Cell Reports. DOI: 10.1016/j.stemcr.2023.05.007

*The content of this communication is the sole responsibility of the Murdoch Children’s and does not reflect the views of the NHMRC.

Journal Link: Stem Cell Reports