On the 11th, it was learned from Nankai University that the research team led by Liu Shulin from the School of Chemistry at the university has developed a new broad-spectrum anti influenza virus strategy. This strategy is based on a technology called "Multiplexing Protein Degradation Targeted Chimeric Molecules (PROTAC)", which can accurately target and synchronously disintegrate the core of influenza virus replication - the viral ribonucleoprotein complex, achieving a "one-stop" attack on multiple key viral components. This achievement provides a powerful, long-lasting, and broad-spectrum treatment plan to overcome the limitations of current anti influenza drugs, such as limited efficacy and susceptibility to drug resistance. The relevant results were recently published in the international journal "Journal of the American Chemical Society". The influenza A virus (IAV) is a major threat to global public health due to its rapid mutation rate and ability to evade host immune responses. At present, anti IAV drugs can only attack a specific target of the virus, which makes it easy for the virus to develop resistance through mutation, significantly limiting the broad-spectrum efficacy and greatly reducing the effectiveness of the drug. The research team cleverly utilized a highly conserved "universal code" in viral RNA - the 5 'untranslated region (UTR). This sequence is extremely stable among different influenza virus strains and is an indispensable "switch" for virus replication. Liu Shulin introduced: "The team has rationally designed a multifunctional PROTAC molecule based on this, which is like a precise 'Trojan horse' that can simultaneously perform tasks of recognition, binding, and guiding degradation. ”One end of the molecule is an oligonucleotide ligand that can precisely bind to the virus's "universal code", while the other end is responsible for recruiting the intrinsic protein "disruptor" (proteasome) in the cell, and tightly connecting the two through optimized linkers. When PROTAC molecules enter infected cells, they can simultaneously hook onto the virus's vRNP complex and the cell's "shredder", thus marking the virus's core protein as "destroyed". Subsequently, the cell's protease will efficiently degrade these key components for virus replication, destroying the virus's replication ability from the source. The results of antiviral research have fully verified the excellent performance of this strategy. PROTAC molecules can effectively inhibit virus replication in a concentration dependent manner, and the inhibitory effect can last for more than 48 hours. Its persistence and efficacy are significantly better than single target control drugs. In addition, this strategy successfully constructed a high genetic resistance barrier by synchronously degrading multiple viral proteins. Virus escape must overcome this obstacle, which is the simultaneous occurrence of effective escape mutations on multiple viral protein targets, forming an escape barrier that viruses find difficult to overcome in natural evolution. Liu Shulin stated that this strategy exhibits broad-spectrum activity against multiple influenza virus strains, further highlighting its potential as a broad-spectrum anti influenza drug. It is reported that this achievement pioneers the advancement of PROTAC technology from single target to multi-target antiviral field, marking a leap from "single pursuit" to "systematic annihilation" of anti influenza strategies and laying the foundation for the development of the next generation of anti influenza drugs. (New Society)