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21, 2020 // -- In a recent study published in the international journal Science Advances, scientists from the University of Texas Center for Health Sciences and others developed a new drug design idea for COVID-19, a key "molecular scissors" that block viruses, a key tool used by viruses to replicate and promote protein invigoration that is important for human immune response. In the
article, researchers developed two specific molecules that effectively inhibit the virus's "molecular scissors", a special enzyme called SARS-CoV-2-PLpro, which promotes the virus's infection process by sensing and processing viruses and human proteins, researcher Shaun K. Dr Olsen points out that the enzyme SARS-CoV-2-PLpro performs a "double whammy" task that stimulates and releases proteins that are essential for virus replication, while also inhibiting the function of molecules such as cytokines and inflammatory degeneration factors that send resistance to infection signals to the immune system in host bodies.
photo source: Shaun K. Olsen, PhD, laboratory at The University of Texas Health Science Center at San Antonio (Joe R. and Teresa Lozano Long School of Medicine) SARS-CoV-2-PLpro can cut off human protein ubibin and ISG15, which helps maintain protein stability, and the enzyme also acts as a molecular scissor, splitting ubiga and ISG15 to reverse the normal effects of the host body.
the study, the researchers also analyzed the three-dimensional structure of enzyme-like SARS-CoV-2-PLpro and two inhibitory molecules (VIR250 and VIR251 molecules), which they said effectively blocked SARS-CoV-2-PLpro. Activity, but it does not identify other similar enzymes in human cells, which may be a key point, that inhibitors are specific to a viral enzyme class and do not cross-react with other human enzymes with similar functions, so specificity will be a key determinant for future scientists to develop more valuable therapies.
addition, the researchers compared enzyme-like SARS-CoV-2-PLpro with similar enzymes in other coronavirus (SARS-CoV-1 and MERS) in recent years, and found that SARS-CoV-2-PLpro enzymes were treated differently from similar enzymes in SARS-1.
one of the key questions is whether this can help effectively explain some of the differences in the mechanisms by which viruses affect humans.
Finally, the researchers say that understanding the similarities and differences in these functions in multiple coronavirus is likely to help us develop inhibitors that can effectively suppress multiple viral infections, and that these inhibitors can potentially be modified to therapeutic effects when other coronavirus appear in the future.
original source: Wioletta Rut, Zongyang Lv, Mikolaj Zmudzinski, et al. Activity profiling and structures of resedor-bound SARS-CoV-2-PLpro protease provides a framework for anti-COVID-19 drug design, Science (2020). DOI: 10.1126/sciadv.abd4596