The researchers found that PLpro protease inhibitors can help stop nCoV from reproducing while reinforcing the antiviral immune response.
NCoV simulation. Photo: Sci Tech Daily.
When passed on to humans, nCoV must overcome a variety of body’s own defense mechanisms, including the innate immune response. During this process, the virus-infected cell releases signalers called type 1 interferons. These attract the natural killer to destroy the infected cell.
One of the reasons nCoV successfully infects is that it can suppress the innate immune response. In addition, it lets human cells produce protease PLpro (an enzyme that allows protein hydrolysis in the body). PLpro has two functions. It plays a role in releasing new viral particles and inhibiting the growth of type 1 interferon. German and Dutch researchers are monitoring this process in cell culture experiments. They found that blocking PLpro not only inhibits viral reproduction, but also enhances the innate immune response of body cells.
“We took compound GRL-0617, a covalent non-covalent PLpro inhibitor, and examined its mode of action biochemically, structurally and functionally. We conclude the inhibition. PLpro is a very promising dual-action Covid-19 remedy. The development of PLpro inhibitors for use in current clinical trials is a major challenge to this treatment direction, ”said Professor. Said Ivan Dikic, director of the Institute of Biochemistry II at the University Hospital of Frankfurt, Germany, and co-authored the study.
Another important finding from the study was that the nCoV PLpro isolated ISG-15 (an interferon-activating gene) from cellular protein with a higher level of activity than SARS virus PLpro (severe acute respiratory distress syndrome). to a stronger inhibition of type 1 interferon production. To find out in detail how PLpro inhibition can suppress the virus, researchers in Frankfurt, Munich, Mainz, Freiburg, and Leiden are working. together and apply biochemistry, structure, information technology and virology. Professor Sandra Ciesek, Director of the Institute of Medical Virology at the University of Frankfurt Hospital, explained that PLpro is an extremely attractive antiviral target because its inhibitory ability will be a dual strike against nCoV.
(According to Sci Tech Daily)