Abstract

Background: Hypochlorous acid (HOCl), which is produced endogenously by neutrophils and other phagocytes, has shown efficacy against a wide range of pathogens in vitro. The aims of this research were to test the virucidal efficacy of SS0330, a new stabilized formulation of HOCl, in an in vivo animal infection treatment and prevention model.

Objectives & Methods: Treatment model: C57BL/6 mice were infected with 6 PFU/30µl Influenza A virus strain A/Puerto Rico/8/1934 (H1N1) on day 0 (n=60), followed by SS0330 or phosphate-buffered saline (PBS) delivered by intranasal inoculation BID for three days. Efficacy was assessed by quantitative polymerase chain reaction (qPCR) from oral swabs and nasal flushes, and by virus plaque titration of homogenized lung. Prevention model: Index C57BL/6 mice infected with recombinant luciferase-expressing Sendai virus were cohoused with naļve C57BL/6 mice (ratio 1:4) on day 1 (n=28). All previously non-infected contact mice received SS0330 or PBS intranasally BID for three days. Efficacy was assessed by bioluminescence using in vivo imaging system (IVIS).

Results: Treatment model: Compared to PBS treated mice, SS0330 treatment reduced 0.5 to 1.1 Log10 lung viral titers on day 3, with corresponding 9.1-, 7.7- and 5.9-fold increases in qPCR Ct values from oropharyngeal swob, nasal flush, and homogenized lung samples, respectively on day 3. Prevention model: On day 3, 10/16 (63%) SS0330 treated mice remained below the lower limit of bioluminescence detection, compared with 3/12 (25%) PBS treated mice.

Conclusion: SS0330 shows virucidal effect in a murine influenza A treatment model, and Sendai post-exposure prophylaxis model.