Methods of treating coronavirus infection
Inventors
Frieman, Matthew • Jarhling, Peter B. • Hensley, Lisa E.
Assignees
University of Maryland Baltimore • US Department of Health and Human Services
Publication Number
US-10434116-B2
Publication Date
2019-10-08
Expiration Date
2035-04-07
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Abstract
The present invention provides methods for treating a coronavirus infection. For example, treatment may be effected by administering a neurotransmitter inhibitor, a signaling kinase inhibitor, an estrogen receptor inhibitor, a DNA metabolism inhibitor or an anti-parasitic agent. Also provided are methods for treating a coronavirus infection in which an anti-viral drug also is administered during any of the described methods.
Core Innovation
The present invention provides methods for treating coronavirus infections by administering therapeutically effective amounts of various pharmaceutical agents including neurotransmitter inhibitors, signaling kinase inhibitors, estrogen receptor inhibitors, DNA metabolism inhibitors, and anti-parasitic agents. Specific examples of coronaviruses treated by these methods include Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Treatments may also involve the concurrent administration of antiviral drugs such as interferons, ribavirin, and others.
The problem addressed by the invention is the lack of approved antiviral or therapeutic treatments for emerging coronavirus infections such as MERS-CoV and SARS-CoV. Prior to 2002, coronaviruses were considered mild pathogens, but the emergence of SARS-CoV and MERS-CoV has demonstrated the need for effective therapeutics. Supportive care was the only current option, with few alternatives available. Existing treatments like ribavirin and interferon have shown limited benefit, and prior art lacks effective compositions and methods to treat respiratory syndrome coronaviruses.
The invention discloses that various classes of drugs, including neurotransmitter antagonists, kinase signaling inhibitors, estrogen receptor antagonists, anti-parasitic agents, and DNA metabolism inhibitors, exhibit antiviral activity against MERS-CoV and SARS-CoV. The methods include administering these agents in therapeutically effective doses to inhibit viral activity by at least 50%, with specific dosing ranges provided. The methods can be applied to both human and non-human subjects and can be administered orally or intravenously either alone or in combination with commonly used antiviral agents.
Claims Coverage
The patent includes one independent claim focusing on the treatment method using kinase signaling inhibitors, with dependent claims specifying particular coronaviruses, inhibition characteristics, dosage ranges, and adjunct antiviral therapy.
Use of kinase signaling inhibitors to treat coronavirus infection
A method of treating coronavirus infection in a subject by administering a therapeutically effective amount of a kinase signaling inhibitor selected from imatinib mesylate, nilotinib hydrochloride, and dasatinib.
Treatment targeting specific coronaviruses
The kinase signaling inhibitor is used to treat Middle East respiratory syndrome coronavirus (MERS-CoV) or severe acute respiratory syndrome coronavirus (SARS-CoV).
Inhibition of viral activity and mechanisms
The kinase signaling inhibitor inhibits viral activity by at least 50%, and functions by inhibiting viral RNA production and/or blocking endosomal fusion during viral entry.
Specified dosage range for kinase signaling inhibitors
The kinase signaling inhibitor is administered in a concentration range of about 50 mg/kg to about 500 mg/kg per day.
Combination therapy with antiviral drugs
The method can further comprise administration of antiviral drugs selected from interferons, ribavirin, adefovir, tenofovir, acyclovir, brivudin, cidofovir, fomivirsen, foscarnet, ganciclovir, penciclovir, amantadine, rimantadine, and zanamivir.
The claims focus on the use of specific kinase signaling inhibitors to treat coronavirus infections by reducing viral activity through mechanisms including viral RNA inhibition and blocking fusion, optionally combined with antiviral drugs at defined dosage ranges.
Stated Advantages
The invention identifies pharmaceutical classes with potential broad antiviral activity against coronavirus infections, including FDA-approved drugs with known safety profiles, facilitating repurposing.
The kinase signaling inhibitors act early in viral lifecycle, potentially blocking viral entry or RNA production, which could lead to effective reduction of viral replication.
Use of neurotransmitter inhibitors like chlorpromazine and anti-parasitic agents like chloroquine demonstrated in vivo protection, reducing weight loss and clinical disease symptoms in SARS-CoV mouse models.
Documented Applications
Treatment of coronavirus infections in humans and non-human subjects, including infections caused by Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV).
Use of kinase signaling inhibitors, neurotransmitter inhibitors, estrogen receptor inhibitors, DNA metabolism inhibitors, and anti-parasitic agents to inhibit viral activity in vitro and protect infected animal models.
Administration of identified agents alone or in combination with approved antiviral drugs for therapeutic intervention in coronavirus infections.
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