Weiss' coronavirus research has encompassed the emerging pathogens severe acute respiratory syndrome, Middle East respiratory syndrome, Human coronavirus OC43, Human coronavirus 229E and the coronavirus disease. These coronaviruses have all evolved to shut downimmune response but have different accessory proteins. Coronaviruses are complex viruses that circulate in animals and occasionally infect humans. They have the largest RNA genome of any viruses, which indicates that they have a wide array of proteins that can attack host cells. Whilst MERS has a viral reservoir in camels and may have been transmitted to humans viacamel handlers, SARS does not have such a specific reservoir. Coronaviruses that occur in humans are primarily viruses of the respiratory tract. Weiss began to work on coronaviruses in the 1980s, when the field was relatively new. She makes use of the murine coronavirus to develop mouse models that allow the study of various pathologies, including viral encephalitis and demyelinating disease. She uses a reverse genetic system to better manipulate the viral genome. Reverse genetics helps to understand the function of a gene through the analysis of phenotypic effects of nucleic acid sequences. She looks to understand what determines coronavirus viral and cellular tropism, as well as better understanding the pathogenesis of coronavirus in the brain. This has involved studies of the interferon antagonists that are encoded by the coronavirus, specifically phosphodiesterase, which antagonises OAS-RNase L immune pathway. Weiss has considered the mechanisms by which the phosphodiesterase antagonises Ribonuclease L. She has studied the role of inflammasome-related cytokines in mouse hepatitis virus-induced disease. Despite murine coronavirus being a useful model of coronaviruses, it is still unclear how mouse hepatitis virus is spread. There is only one receptor for the mouse hepatitis virus – the carcinoembryonic antigen – but highly virulent strains of the virus can spread even when this receptor is not present. In 2020, Weiss was made co-Director of the University of Pennsylvania Center of Research for Coronaviruses and Other Emerging Pathogens. The Center looks to accelerate research that focusses on SARS-CoV-2, become a centralised repository of SARS-CoV-2 research and create new opportunities to fund research relating to SARS-CoV-2. SARS-CoV-2 is different to SARS; as there are many people who have mild or asymptomatic coronavirus disease without being aware that they have it. Whereas in the case of SARS, patients were too unwell to leave their homes, and either seriously self-isolated, were cared for, or died. In March 2020 Weiss was awarded certification from the Centers for Disease Control and Prevention to work with the SARS-CoV-2 virus in a BSL 3 laboratory at the University of Pennsylvania. As well as investigating potential antivirals, the Weiss laboratory are studying the evolution of the virus.
