Prevention and treatment of influenza infections
Influenza viruses are responsible for most of the respiratory infections leading to significant mortality and morbidity annually. The available antiviral agents against influenza viruses are clinically rather ineffective, and the emergence of drug-resistant strains calls for the development of novel and potentially more effective prevention and treatment strategies. Influenza viruses use host proteins for infection. Transmembrane serine proteases are crucial for influenza virus infection as they activate the virus through proteolytic cleavage of influenza hemagglutinin into infection-competent fusogenic conformation.
TMPRSS2 is a type II transmembrane serine protease, which has been shown to activate various influenza strains by proteolytic cleavage in epithelial tissues of the respiratory tract. Inhibition of TMPRSS2 can be a new strategy for preventing and treating influenza infection with reduced potential for developing drug resistance. TMPRSS2 knock-out mice and pigs are significantly more resistant to influenza infections than the wild type animals.
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 protease with high efficiency in in vitro experiments.