Prevention and treatment of SARS-CoV-2 infection
During SARS coronavirus (SARS-CoV, MERS-CoV, SARS-CoV-2) infection the viruses use host proteins to infect humans. TMPRSS2 is a cell-surface protease which plays an essential role in the coronavirus infection. The viruses bind to ACE2 on the host cell surface through their spike protein. Efficient cell entry depends on spike protein priming by TMPRSS2, which is a prerequisite for virus coat – cell membrane fusion. TMPRSS2 is heavily expressed in the airway epithelium and lung tissues promoting severe respiratory complications during SARS-CoV-2 infections. Severe lung complications are the leading cause of death among COVID-19 patients. It is of utmost importance to develop novel therapeutic strategies to prevent and control the coronavirus infection.
Inhibiting TMPRSS2 can prevent and treat SARS-CoV-2 infection. TMPRSS2 inhibitors have been shown to prevent SARS-CoV-2 infections in cell culture and animal experiments, and there are ongoing clinical trials. However, these are non-selective inhibitors. EvolVeritas developed a unique proprietary technology to produce active TMPRSS2 and developed selective and efficient inhibitors against TMPRSS2 by directed protein evolution. These inhibitors block the activity of TMPRSS2 with high efficiency in in vitro experiments, and also successfully reduce SARS-CoV-2 infection in cell culture.