Host proteases necessary for human parainfluenza virus spread in human lung

This technology identifies proteases that are essential for infection and propagation of the human parainfluenza virus (HPIV) in the lung and describes a method of treating HPIV with serine protease inhibitors.

Unmet Need: Targeting treatments for human parainfluenza virus proliferation and treatment

There are currently no vaccines and treatments for the human parainfluenza virus (HPIV). The mechanisms of activation and propagation of HPIV3 in the lung is poorly understood. Thus, elucidating the essential factors of HPIV3 spread the mechanisms of propagation may identify methods for HPIV3 treatment.

The Technology: Identification of essential proteases in parainfluenza spread and inhibitor treatment

This technology identifies two serine proteases that cleave viral furin proteins to allow the spread and proliferation of the human parainfluenza virus in the human lung. Facilitation of transmembrane proteases that target TMPRSS2 and TMPRSS4 expression are important for cleavage of HPIV3 fusion protein in the human lung. Serine protease inhibitors, including nafamostat, reduced HPIV3 spread in nasal tissue of cotton rats and thus may be utilized as methods to prevent or treat HPIV.

This technology has been validated in vivo in cotton rats.

Applications:

• Target for human parainfluenza virus (HPIV) vaccines
• Research model for viral spread and proliferation in lung cells
• Mechanism of action identified for identification of antiviral and pharmacological agents

Advantages:

• Identification of essential proteases in human parainfluenza virus (HPIV) spread and proliferation in the lung
• Target for human parainfluenza virus treatment
• Effective inhibitors of HPIV spread

Lead Inventor:

Anne Moscona, M.D.

Patent Information:

Patent Pending (WO/2023/220712)

Related Publications:

• Greninger AL, Rybkina K, Lin MJ, Drew-Bear J, Marcink TC, Shean RC, Makhsous N, Boeckh M, Harder O, Bovier F, Burstein SR, Niewiesk S, Rima BK, Porotto M, Moscona A. Human parainfluenza virus evolution during lung infection of immunocompromised individuals promotes viral persistence. J Clin Invest. 2021 Dec 1; 131(23): e150506.

• Outlaw VK, Cheloha RW, Jurgens EM, Bovier FT, Zhu Y, Kreitler DF, Harder O, Niewiesk S, Porotto M, Gellman SH, Moscona A. Engineering Protease-Resistant Peptides to Inhibit Human Parainfluenza Viral Respiratory Infection. J Am Chem Soc. 2021 Apr 21; 143(15): 5958-5966.

• Marcink TC, Wang T, des Georges A, Porotto M, Moscona A. Human parainfluenza virus fusion complex glycoproteins imaged in action on authentic viral surfaces. PLoS Pathog. 2020 Sep 21; 16(9):e1008883.

• Outlaw VK, Bottom-Tanzer S, Kreitler DF, Gellman SH, Porotto M, Moscona A. Dual Inhibition of Human Parainfluenza Type 3 and Respiratory Syncytial Virus Infectivity with a Single Agent. J Am Chem Soc. 2019 Aug 14; 141(32):12648-12656.

Tech Ventures Reference:

• IR CU22326

• Licensing Contact: Kristin Neuman