BHH-VHL TMPRSS2 PROTAC d1 for COVID-19

Proteolysis-targeting chimera (PROTAC) technology has demonstrated remarkable progress in tumor therapy, attributed to its unique capability of catalytically degrading “undruggable” targets. In the context of the ongoing global health threat posed by the Coronavirus Disease 2019 (COVID-19) pandemic, the application scope of PROTAC technology has been gradually extended to the field of antiviral research. Unlike traditional small molecule inhibitors, PROTAC employs an “event-driven” mechanism to achieve ubiquitination-mediated degradation of target proteins. This approach holds great promise in addressing challenges such as drug resistance, targeting host-dependent factors, and high-mutagenic viral proteins. This article provides a comprehensive review of the application progress of PROTAC technology in antiviral therapy, with a particular emphasis on successful cases across a range of viral pathogens, including Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), influenza virus, and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Additionally, it delves into the challenges encountered in this field and ponders future development directions. Through the integration of the latest research findings, this article proposes a dual-target degradation strategy based on the host–pathogen interaction interface. These proposals aim to offer theoretical support for the clinical translation of antiviral PROTACs.