Use of low dose emetine for inhibition of human cytomegalovirus (HCMV)
Inventors
Boger, Ravit • Ferrer, Marc • Marugan, Juan • Garcia, Andres Dulcey • Southall, Noel Terrence • Hu, Xin
Assignees
Johns Hopkins University • US Department of Health and Human Services
Publication Number
US-11253511-B2
Publication Date
2022-02-22
Expiration Date
2037-01-04
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Abstract
The present invention relates to the field of virology. More specifically, the present invention provides methods and compositions useful for prevention and treatment of human cytomegalovirus (CMV). In one embodiment, a pharmaceutical composition comprises (a) emetine or a derivative thereof; (b) a human cytomegalovirus (HCMV) drug; and (c) a pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical composition further comprises an adjuvant. In a specific embodiment, the HCMV drug is ganciclovir. In such embodiments, emetine is present at about 1/10 to about 1/100 the normal dosage for amebiasis.
Core Innovation
The invention provides methods and compositions useful for the prevention and treatment of human cytomegalovirus (HCMV). Specifically, the invention employs low doses of emetine or its derivatives, alone or in combination with human cytomegalovirus drugs such as ganciclovir, and pharmaceutically acceptable carriers. The compositions may also include adjuvants to enhance treatment efficacy.
The invention addresses the problem of limited approved drugs for HCMV therapy, which are all viral DNA polymerase inhibitors with notable side effects and the emergence of resistant viral mutants during therapy. These issues create a pressing need to develop anti-HCMV compounds with novel mechanisms of action.
Claims Coverage
The patent includes three claims focusing on the composition and methods of treatment involving emetine and ganciclovir, highlighting their combination and specific formulation features.
Pharmaceutical composition comprising emetine, ganciclovir, and a pharmaceutically acceptable carrier
A synergistic pharmaceutical composition that contains (a) emetine; (b) ganciclovir; and (c) a pharmaceutically acceptable carrier.
Inclusion of an adjuvant in the pharmaceutical composition
The pharmaceutical composition further comprises an adjuvant alongside emetine, ganciclovir, and a pharmaceutically acceptable carrier.
Methods for treating human cytomegalovirus with the synergistic composition
A method of treating HCMV in a patient by administering the synergistic pharmaceutical composition containing emetine and ganciclovir.
Method of treatment using therapeutically effective amounts of emetine and ganciclovir with synergistic effect
A method for treating HCMV by administering a therapeutically effective amount of emetine in combination with ganciclovir, where the combination produces a synergistic effect in treating HCMV.
The claims cover pharmaceutical compositions combining emetine and ganciclovir with or without adjuvants, and methods for treating HCMV by administering such compositions or combinations, emphasizing the synergistic antiviral effect of emetine and ganciclovir.
Stated Advantages
Emetine inhibits HCMV replication at very low drug concentrations with high selectivity index.
Emetine exhibits a novel mechanism of action different from current HCMV inhibitors, acting early after virus entry but before DNA replication.
Emetine shows efficacy in vivo at very low doses with a long half-life and high tissue concentrations, resulting in good tolerability in mouse models.
Combination of emetine with ganciclovir provides synergistic antiviral activity against HCMV.
Using low doses of emetine significantly reduces potential toxicity compared to doses previously used for other indications.
Documented Applications
Prevention and treatment of human cytomegalovirus (HCMV) infection.
Treatment of herpes simplex virus (HSV) types 1 and 2.
Potential use for Epstein-Barr virus (EBV) and Kaposi's Sarcoma-Associated Herpesvirus (KHSV).
Prophylaxis and therapy in transplant recipients and immunocompromised patients at risk of HCMV.
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