ABSTRACT
Due to its fast international spread and substantial mortality, the coronavirus disease COVID-19 evolved to a global threat. Since there is currently no causative drug against this viral infection available, science is striving for new drugs and other approaches to treat the new disease. Studies have shown that the cell entry of coronaviruses into host cells takes place through the binding of the viral spike (S) protein to cell receptors. Priming of the S protein occurs via hydrolysis by different host proteases. The inhibition of these proteases could impair the processing of the S protein, thereby affecting the interaction with the host-cell receptors and preventing virus cell entry. Hence, inhibition of these proteases could be a promising strategy for treatment against SARSCoV- 2. In this review, we discuss the current state of the art of developing inhibitors against the entry proteases furin, the transmembrane serine protease type-II (TMPRSS2), trypsin, and cathepsin L.
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Humans , Serine Proteases , Spike Glycoprotein, Coronavirus/metabolism , Virus InternalizationABSTRACT
The SARS-CoV-encoded papain-like cysteine protease (PLpro) plays crucial roles in viral replication and maturation processes. It is required to cleave the precursor polyproteins into functional proteins. Thus, it is considered to be a promising target for developing specific drugs. For rational optimization of hit compounds, information about the structure-activity relationship (SAR) is fundamental. Herein, we characterize isoindolines as a new class of PLpro inhibitors.