Novel Cardiac Glycoside Analogs as Anti-Human Cytomegalovirus (HCMV) Agents

Novelty: Novel group of cardiac glycosides shown to have effective anti-HCMV properties for HCMV infection treatment.
 
Value Proposition: HCMV infection is a serious problem in organ transplant patients and congenitally-infected babies. The currently available systemic therapies for HCMV targeting the viral DNA polymerase are associated with significant side effects and emergence of resistant viral strains. This invention identifies a class of cardiac glycosides as host-targeted therapeutics for HCMV. Additional advantages include:

• Circumvents the problem of resistant viral strains
• No side effects
• Highly potent inhibitors of HCMV
• Can be used in combination with other HCMV treatments

 
Technical Details: Johns Hopkins researchers have identified digoxin and digitoxin analogs, which belong to a class of cardiac glycosides, as potent anti-CMV pharmaceuticals. Substantial evidence supports the role of cardiac glycosides as anti-cancer agents and that these anti-cancer activities likely depend on the 3 isoform of the Na+/K+ ATPase. For HCMV, preferential upregulation of the 3 isoform of the Na+/K+ ATPase has been shown, as well as its decreased expression when treated with digitoxin. Since isoform specificity has been linked to the length of the sugar chain of the cardiac glycosides, a variety of newly synthesized digitoxin analogs with varied sugar chains were tested for anti-HCMV activities. In vitro assay results confirmed that all tested compounds were highly potent inhibitors of HCMV replication at nM concentrations.
 
Looking for Partners: To develop & commercialize the technology as anti-HCMV therapeutics.
 
Inventors: Ravit Boger
 
Patent Status: Pending US Application US-2016-0143934
 
Stage of Development: Discovery
 
Data Availability: Under CDA / NDA
 
Publications/Associated Cases: PMC4027591 

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