Use of Rostafuroxin to Inhibit Viral Infection
This invention relates to a broadly antiviral small chemical molecule, Rostafuroxin, expected to be well tolerated in humans and available for clinical evaluation. In particular, this patent application relates to the novel and unexpected finding that Rostafuroxin substantially inhibits RSV infection. ATP1A1 is a host protein involved with cellular entry of RSV. RSV entry was found to require activation of a signaling cascade mediated by ATP1A1 which resembles the signaling pathway (also mediated by ATP1A1) triggered by cardiotonic steroids. Though not evaluated for RSV, ATPA1A was previously implicated as a pro-viral factor in the infection cycles of a number of viruses, but the nature of its involvement and mechanism of action were unknown.
Rostafuroxin, a synthetic digitoxigenin derivative, is a small-molecule that is known to specifically bind ATP1A1. It has not been previously known to have any antiviral activity.
The inventors have evidence that Rostafuroxin inhibits RSV infection in respiratory epithelial cells. Rostafuroxin inhibits RSV induced ATP1A1-mediated signaling pathway required for RSV entry. This was demonstrated in A549 cells, a widely used human respiratory epithelial cell line, and in primary human airway epithelial cells derived from a healthy human.
Rostafuroxin has been previously tested in clinical studies as an anti-hypertensive agent. It has no adverse effects in healthy humans and, importantly, does not lower the normal systolic blood pressure of healthy individuals. Rostafuroxin is a promising anti-viral drug candidate for RSV and possibly other viruses that use the same pathway for host cell entry.
This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404, as well as for further development and evaluation under a research collaboration.
- Viral therapeutics
- Viral diagnostics
- Vaccine research
- Ease of manufacture
- Broad antiviral activity
- Favorable safety profile in clinical trials