Respiratory syncytial virus (RSV) is highly ocntagious and the second leading cause of lower respiratory tract infections in children, requiring hospitalization of about 3% of children under age 2 and with a mortality rate reported to be approximately 5x higher than influenza. RSV also poses significant risk to the elderly with a mortality rate of 11-18%. Despite the high rate of hospitalization and. mortality, no specific antiviral treatment exists to combat RSV infection and treatment primarily focuses on symptom management and supportive care.

The oral bacteria Porphyromonas gingivalis (Pg) produces three trypsin-like cysteine proteases called gingipains. These include arginine specific gingipains, HRgpA and RgpB, and lysine specific gingipain, Kgp, that will cleave at exposed arginine (Arg-Xaa) or lysine (Lys-Xaa) peptide bonds, respectively. Insertion of a polyhistidine (His) tag upstream of the C-terminal domain cleavage site of each of the three gingipains allows for high yield and specific purification of the gingipains from Pg culture, and it has been confirmed that insertion of the His tag has no effect on proteolytic activity. Here, the inventors show that these gingipains inactive respiratory syncytial virus (RSV) via cleavage, and thus inactivation, of the RSV attachment protein G and fusion protein F. This gingipain-mediated proteolysis results in RSV being unable to adhere/ infect bronchial epithelial cells, thereby limiting infection. It is proposed that these gingipains could be used as antivirals to limit RSV infectivity. Thus far, the inventors have demonstrated the antiviral/ protective effects in vitro in human 3D cultures and in mouse models of viral lung infection.

Gingipains could be developed as a drug complexed with nanoparticles or nebulized to target RSV in the case of severe lung infection. Given the broad specificity of gingipain-mediate cleavage, this could be expanded and applied in other contexts of highly contagious respiratory viruses, including SARS-CoV-2, influenza, rhinovirus, and metapneumovirus.