In the case of an infection, the SARS-CoV-2 virus must succeed over the defense mechanisms of the human body, adding its innate or non-specific immune defense. During this process, inflamed frame cells release messenger ingredients called type 1 interferons. These attract herbal killer cells, which kill inflamed cells.
One of the reasons SARS-CoV-2 is so effective (and harmful) is that it can suppress the non-specific immune reaction. In addition, it allows the human mobile to produce the viral protein PLpro (papain protease). PLpro has two functions: it plays a role in the maturation and release of new viral particles and suppresses the progression of type 1 interferons. German and Dutch researchers have now been able to stick to these processes in mobile culture experiments. In addition, blocking PLpro inhibited virus production while strengthening the innate immune reaction of human mobiles. The molecular dynamics calculations of Laura Schulz and Ahmad Reza Mehdipour at the Max Planck Institute for Biophysics and the Max Planck Computing and Data Facility in Garching have played a major role in elucidating the underlying mechanism and a greater understanding of inhibitor binding.
Promising healing strategy
“We use grL-0617, a non-covalent PLpro inhibitor, and test its mode of action very intensely in terms of biochemistry, design and function. We conclude that inhibition of PLpro is a very promising double-hit healing strategy opposite COVID-19. The progression of PLpro inhibitor ingredient categories for use in clinical trials is now a major challenge for this curative approach.”
Another location of these paints is that the PLpro viral protein of SARS-CoV-2 clive ISG-15 (interferon-stimulated gene 15) of cellular proteins with a higher point of activity than the SARS equivalent, leading to greater inhibition of type Yo interferon production. This is consistent with recent clinical observations that COVID-19 has a reduced reaction to interferon compared to other respiratory viruses such as influenza and SARS.
To perceive in detail how the inhibition of PLpro stops the virus, researchers from Frankfurt, Munich, Mainz, Freiburg and Leiden worked intensively in combination and combined their biochemical, structural, computer and virological experience.