TMPRSS2 protein, a novel target for SARS-CoV-2 drugs AntiviralDrug Coronavirus Disease COVID pathology Nature Uni_MR
By Dr. Liji Thomas, MDJul 28 2022Reviewed by Benedette Cuffari, M.Sc. As scientists continue to develop preventive and therapeutic compounds to treat infection with the severe acute respiratory syndrome coronavirus 2 , a new Signal Transduction and Targeted Therapy journal study reports on the activity of a compound which inhibited the host cell serine protease transmembrane serine protease 2 , ultimately preventing severe coronavirus disease 2019 .
Repeated booster vaccine doses have been recommended to maintain antibody levels at adequately high levels. Monoclonal antibodies have also been approved to prevent severe disease in high-risk infected individuals; however, most have lost their efficacy in Omicron infections. The second cleavage involves TMPRSS2 at the S2’ site and occurs after receptor binding, which exposes the cleavage site upstream of the fusion peptide. This cleavage allows membrane fusion to occur, subsequently leading to the entry of the virus into the host cell by endocytosis.
Related StoriesIn mouse models expressing the humanized K18-hACE2 receptor, pretreatment with N-0385 reduced the severity of illness and mortality rate from SARS-CoV-2 infection. Similar results were obtained when treatment was provided after viral inoculation, with a single dose at 12 hours from Delta inoculation proving capable of reducing weight loss and viral loads.
Secondly, N-0385 could be useful in treating infections with other viruses that use host TMPRSS2 as well, such as the influenza virus or other coronaviruses. Recently, the structure of this enzyme was unveiled, which could pave the way for more specifically designed inhibitors.
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