In a groundbreaking discovery, scientists at the Walter and Eliza Hall Institute (WEHI) have developed an antiviral compound that successfully prevents long-term symptoms of Long COVID in mice. This world-first study highlights the potential for a future treatment targeting this debilitating condition, which affects millions globally. The research also demonstrates superior efficacy compared to current treatments like Paxlovid, suggesting it could revolutionize acute and post-acute care for SARS-CoV-2 infections. By identifying a novel drug target, PLpro, researchers hope their findings will pave the way for clinical trials and ultimately provide relief for those suffering from Long COVID.

A multidisciplinary team at WEHI has made significant strides in combating Long COVID, a chronic illness characterized by persistent symptoms such as brain fog, fatigue, and respiratory issues. Dr. Marcel Doerflinger, leading the investigation, explained that approximately 5% of individuals infected with SARS-CoV-2 develop Long COVID, turning it into what he calls "a silent pandemic." Through pre-clinical studies conducted on specialized mouse models, the team discovered that their newly formulated antiviral not only mitigates acute symptoms but also prevents long-term organ dysfunction in the brain and lungs.

The breakthrough centers around PLpro, a protein identified by Professor David Komander and his colleagues as a promising therapeutic target. Unlike existing treatments focused on Mpro, PLpro offers unique advantages in blocking viral replication. To accelerate development, the National Drug Discovery Centre (NDDC), headquartered at WEHI, screened over 400,000 compounds, uncovering potent inhibitors capable of overcoming previous limitations in drug design. According to Prof Komander, this rapid advancement showcases the power of cutting-edge technology combined with collaborative scientific efforts.

Co-first author Dr Shane Devine emphasized the dual benefits of the new compound—treating both acute and long-term effects of the virus more effectively than current options. Current therapies like Paxlovid face challenges due to their reliance on multiple interacting compounds, limiting accessibility and compatibility with other medications. Moreover, the ever-evolving nature of SARS-CoV-2 underscores the urgency for alternative solutions. “Our findings indicate that targeting PLpro could bridge critical gaps in treating both acute and chronic manifestations of the disease,” said Dr Devine.

Looking ahead, the project will continue partnerships with institutions like the Centre for Drug Candidate Optimisation (CDCO) and Monash Institute of Pharmaceutical Sciences (MIPS) to refine the compound’s pharmaceutical properties. Supported by organizations including the Medical Research Future Fund and Wellcome Trust, this research holds immense promise for transforming patient outcomes worldwide.

This pioneering work represents a crucial step toward addressing the global health burden posed by Long COVID. By validating PLpro as a viable drug target and showcasing the efficacy of their novel compound, WEHI researchers are laying the groundwork for transformative therapies. Their dedication to advancing science may soon translate into tangible benefits for patients struggling with prolonged illness following SARS-CoV-2 infection.