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WO2009106839A1 - Utilisation de la tiamuline en tant qu’agent antiviral - Google Patents

Utilisation de la tiamuline en tant qu’agent antiviral Download PDF

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Publication number
WO2009106839A1
WO2009106839A1 PCT/GB2009/000548 GB2009000548W WO2009106839A1 WO 2009106839 A1 WO2009106839 A1 WO 2009106839A1 GB 2009000548 W GB2009000548 W GB 2009000548W WO 2009106839 A1 WO2009106839 A1 WO 2009106839A1
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WIPO (PCT)
Prior art keywords
virus
infection
use according
influenza
tiamulin
Prior art date
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Ceased
Application number
PCT/GB2009/000548
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English (en)
Inventor
Thomas David Kay Brown
Amanda Demse Stuart
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Cambridge Enterprise Ltd
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Cambridge Enterprise Ltd
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Filing date
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Publication of WO2009106839A1 publication Critical patent/WO2009106839A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones

Definitions

  • the invention relates to the use of an antibiotic in the preparation an antiviral medicament.
  • the invention also relates to a method of treating a viral infection comprising administering an antibiotic to a subject having a viral infection.
  • Tiamulin is a diterpene antibiotic with a pleuromutilin structure similar to valnemulm. Tiamulin has the following structure:
  • Tiamulin is used for the treatment and prophylaxis of a number of diseases such as dysentery, pneumonia and mycoplasmal infections in pigs and poultry. Its activity is understood to be largely confined to gram positive bacteria and mycoplasma.
  • PRRS porcine reproductive and respiratory syndrome
  • PRRS is often complicated by a bacterial infection, particularly an infection with
  • M-hyo Mycoplasma hyopneumoniae
  • tiamulin can be used to treat PRRSV itself.
  • the inventors have found that tiamulin has a direct effect on the virus.
  • tiamulin has only been used to treat bacterial infections such as M-hyo. Tiamulin has not been used to treat viral infections. Although tiamulin has been used to treat M-hyo in pigs with PRRS, it was not known that it could have an effect on the virus as well as on the bacterial infection.
  • Tiamulin is a pleuromutilin antibiotic.
  • Other pleuromutilin antibiotics have not been found to have an effect on viruses.
  • valnemulin a pleuromutilin to which tiamulin is closely related has been tested by the inventors and does not have effects on either PRRSV or Influenza.
  • tiamulin or a functional derivative, metabolite, ester or salt thereof, in the preparation of a medicament for the prevention or treatment of an infection with a virus.
  • Tiamulin is well known in the art.
  • Derivatives and metabolites of tiamulin include any compounds closely related to tiamulin or which tiamulin becomes when in solution or when administered to a subject.
  • Derivatives and metabolites of tiamulin include 8-alpha- hydroxytiamulin.
  • tiamulin When tiamulin is present in the form of a pharmaceutically acceptable ester, an alkyl ester thereof is preferred. When tiamulin is present in the form of a pharmaceutically acceptable salt, any appropriate salt may be used. Salts formed with organic acids are preferred, especially salts formed with acids such as ascorbic, glycolic, lactic, malic, tartaric or citric acid.
  • tiamulin Functional derivatives, metabolites, esters and salts function in the same way as tiamulin, that is to say, they have a similar effect on a particular viral infection. It is particularly preferred that the invention relates to the use of tiamulin, or an ester or salt thereof, in the preparation of a medicament for the prevention or treatment of an infection with a virus.
  • infection with a virus means the presence in a host of viral particles. Ih particular, it means the presence in a subject of viral particles not normally found in that host or of viral particles that are pathogenic or cause disease in the host.
  • Prevention of an infection with a virus means that there is a reduction of the number of viral particles in a host, or reduction or prevention of replication of viral particles in a host, or reduction or prevention of the cytopathic effect of virus reproduction, or reduction or prevention of entry of the virus into the cell cytoplasm, or the reduction or prevention of pathological effects or signs /symptoms of the viral infection, when compared to the expected status of an untreated host following exposure to the virus.
  • An untreated host is a host that has not received the medicament prepared in accordance with the invention.
  • the expected status is the likely number of viral particles, or level of cytopathic effects, or pathological effects or signs/ symptoms in an untreated host following exposure to the virus.
  • One skilled in the art would be able to predict this.
  • Treatment of an infection with a virus means that there is a reduction of the number of viral particles in a host, or reduction or prevention of replication of viral particles in a host, or reduction or prevention of the cytopathic effect of virus reproduction, or reduction or prevention of entry of the virus into the cell cytoplasm, or the reduction or prevention of pathological effects, clinical signs or symptoms of the viral infection, when compared to the status prior to treatment.
  • the reduction is preferably statistically significant. For example, there is preferably a reduction of at least 25%, more preferably at least 30%, even more preferably at least 35%, most preferably at least 40%.
  • a host is a higher organism, the cells of which are used by the virus to replicate itself.
  • the host may be a human or an animal. It is preferred that the host is an animal, especially a livestock animal such as a cow, horse or pig. It is particularly preferred that the host is a pig. Alternatively, the host is preferably a human.
  • the virus is preferably a virus that uses the endosomal or lysosomal pathway to infect host cells.
  • endosomal pathway and lysosomal pathway are well known in the art. They refer to mechanisms used by some viruses to enter cells. All viruses must have ways of entering target cells in order to initiate replication. Viruses generally do this in two ways, either by a direct mechanism at the cell's plasma membrane, or following internalisation into a cellular compartment such as an endosome or a lysosome. Viruses that use endosomes and lysosomes to enter the cell must also fuse with or penetrate the endosomal or lysosomal membrane in order to be released into the cell cytoplasm.
  • An endosome is an organelle that carries materials newly ingested by endocytosis. The term is well known in the art.
  • a lysosome is an organelle that contains degradative enzymes. The term is well known in the art.
  • tiamulin enters cells and concentrates in endosomes and lysosomes and affects the pH in those endosomes and lysosomes.
  • the inventors believe that this change in the endosome or lysosome pH prevents the fusion of viral particles within the endosome or lysosome with the endosome or lysosome membrane and hence prevents the virus from entering the cell cytoplasm and replicating.
  • the virus is preferably a virus that uses the late endosomal pathway or lysosomal pathway.
  • a late endosome is a prelysosomal organelle.
  • the term late refers to the amount of time it takes for endocytosed molecules to be delivered to the late endosome. Late endosomes are more spherical than early endosomes and are positioned close to the nucleus. Late endosomes have a more acidic pH than early endosomes. The term late endosome is well known in the art.
  • the virus is preferably a virus that uses an endosomal or lysosomal pathway controlled by Rab7.
  • Rab proteins are small GTPases found at the cytoplasmic face of certain cellular compartments. They have a role in the regulation of trafficking across the membrane of those compartments. Rab7 has a role in the regulation of trafficking in late endosomes and lysosomes.
  • the virus is preferably a virus that requires a pH within the endosome or lysosome of below 6.5, preferably below 6, more preferably below 5.5, even more preferably below 5, most preferably below 4.5.
  • the pH of the endosome or lysosome can be measured using a pH sensitive dye, for example one which fluoresces blue at neutral pH and yellow/green at low pH.
  • a pH sensitive dye for example one which fluoresces blue at neutral pH and yellow/green at low pH.
  • the ratio of blue:yellow provides a measure of the endosome/lysosome pH (Diwu, Chen, Zhang, Klaubert and Haughland (1999) Chemistry and Biology VoI 6 Issue 7 411-418).
  • a virus uses the endosomal or lysosomal pathways to achieve cell entry.
  • one skilled in the art can confirm whether a virus uses the endosomal or lysosomal pathway, check which part of the pathway is used or confirm pH or Rab protein dependence by testing viral entry into cells in the presence of compounds that are known to alter endosomal or lysosomal pH, or by using mutants that are negative for a particular Rab protein.
  • the following chemical inhibitors may be used: • Chloroquine and ammonium chloride, which raise endosomal pH by acting as proton sinks; and
  • Nocodazole which depolymerises microtubules and blocks transition from early endosome to late endosomes. If a virus does not achieve cell entry in the presence of chloroquine or ammonium chloride, it can be considered to be pH dependent, requiring an acidic pH to infect cells. If a virus is prevented from infecting cells by nocodazole, it can be considered to use the late endosome pathway or lysosome pathway to enter cells, its entry to these pathways being blocked by the nocodazole. Alternatively, the following dominant negative mutants may be used:
  • rab7 T22N mutant which blocks transition from early endosomes to late endosomes
  • Viruses inhibited by the rab5 S34N mutant require passage through an early endosome, at a pH 6.5.
  • Viruses inhibited by the rab7 T22N mutant require passage through a late endosome at pH 5.
  • the virus may be, for example, a virus from any of the following families: Adenoviridae, Arteriviridae, Asfarviridae, Bunyaviridae, Circoviridae, Coronaviridae, Flaviviridae, Orthomyxoviridae, Parvoviridae, Picornaviridae, Reoviridae, and Togaviridae.
  • the virus may be, for example, a virus from any of the following genera: Mastadenovirus, Arterivirus, Asfarvirus, Hantavirus, Circovirus, Coronavirus, Flavivirus, Pestivirus, Hepacivirus, Influenza virus A, Isavirus, Parvovirus, Enterovirus, Rhinovirus, Orthoreovirus, Rotavirus, and Alphavirus.
  • virus may mean any one or more of, or any combination of adenovirus 7, PRRSV, equine arteritis, influenza, including human, avian, swine, horse, bovine and dog influenza, salmon anaemia virus, classical swine fever, Hepatitis C virus, Hepatitis E virus, African swine fever virus, Puumala virus, infectious bronchitis virus, transmissible gastroenteritis, SARS CoV, West Nile virus, yellow fever virus, tick borne encephalitis virus, bovine diarrhoea virus, canine parvovirus, Coxsackie B3, Coxsackie B5, avian reo virus, rotavirus, Semliki forest virus, porcine circo type 2, Ebola and Marburg viruses.
  • the virus is preferably PRRSV.
  • the virus is preferably not PRRSV.
  • influenza is preferably influenza, especially human influenza, particularly human influenza strain A or B, especially strain A.
  • the invention provides the use of tiamulin or a functional derivative, metabolite, ester or salt thereof in the preparation of a medicament for the treatment of any one or more of, including any combination of, adenovirus 7, PRRSV, equine arteritis, influenza, including human, avian, swine, horse, bovine and dog influenza, salmon anaemia virus, classical swine fever, Hepatitis C virus, Hepatitis E virus, African swine fever virus, Puumala virus, infectious bronchitis virus, transmissible gastroenteritis, SARS CoV, West Nile virus, yellow fever virus, tick borne encephalitis virus, bovine diarrhoea virus, canine parvovirus, Coxsackie B3, Coxsackie B5, avian reovirus, rotavirus, Semliki forest virus, porcine circo type 2, Ebola virus and Marburg viruses.
  • adenovirus 7, PRRSV equine art
  • the invention provides the use of tiamulin, or a functional derivative, metabolite, ester or salt thereof, in the preparation of a medicament for the prevention or treatment of an infection with a virus as defined herein and the prevention or treatment of a bacterial infection.
  • the prevention or treatment of an infection with a virus may be simultaneous with, or subsequent or prior to the prevention or treatment of a bacterial infection.
  • bacterial infection means the presence in a host of bacteria. In particular, it means the presence in a subject of bacteria not normally found in that host or of bacteria that are pathogenic or cause disease in the host or the presence of such bacteria in a location within the host in which the bacteria are not normally found.
  • Prevention of a bacterial infection means that there is a reduction of the number of bacteria in a host, or reduction or prevention of replication of bacteria in a host, or the reduction or prevention of pathological effects or clinical signs or symptoms of the bacterial infection, when compared to the expected status of an untreated host following exposure to the bacteria.
  • An untreated host is a host that has not received the medicament prepared in accordance with the invention.
  • the expected status is the likely number of bacteria or pathological effects or clinical signs or symptoms in an untreated host following exposure to the bacteria.
  • One skilled in the art would be able to predict this.
  • Treatment of a bacterial infection means that there is a reduction of the number of bacteria in a host, or reduction or prevention of replication of bacteria in a host, or the reduction or prevention of pathological effects or clinical signs or symptoms of the bacterial infection, when compared to the status prior to treatment.
  • the bacterial infection may be any infection that is susceptible to treatment with tiamulin or a functional metabolite, derivative, ester or salt thereof.
  • the bacterial infection may be an infection with any one or more of the following bacteria:
  • Mycoplasma species (M.hyopneumoniae, M. hyosynoviae, M.hyorhinis M.gallisepticum, M synoviae, M. meleagridis, M. bovis, M. hovirhinis )
  • Streptococci Streptococci (Strep.suis, Strep, pyogenes,) Staphylococci ⁇ Staph, aureus, Staph, epidermidis,)
  • Clostridium perfringens Clostridium species
  • the bacterial infection is preferably an infection with a mycoplasma species, especially Mycoplasma hyopneumoniae.
  • PRDC Porcine Respiratory Disease Complex
  • PRRSV Porcine Respiratory Disease Complex
  • Porcine circovirus type 2 Swine influenza
  • Porcine coronavirus and pseudorabies virus Aujeszky's
  • the bacterial pathogens Mycoplasma hyopneumoniae, Actinobacillus pleuropneumonias, Pasteurella multocida, Streptococcus suis and Bordetella brochiseptica.
  • the viral infection is an infection with PPRSV and/or swine influenza
  • the bacterial infection is preferably an infection with one or more of Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Pasteurella multocida, Streptococcus suis or Bordetella brochiseptica.
  • Mycoplasma bovis may also exacerbate this disease.
  • the viral infection is an infection with bovine virus diarrhoea virus
  • the bacterial infection is preferably an infection with Mannheimia (Pasteurella) haemolytica or Mycoplasma bovis
  • the viral infection is an infection with avian influenza
  • the bacterial infection is preferably an infection with Mycoplasma gallinarum.
  • Influenza virus infection in man can predispose the individual to secondary bacterial infections such as Staphylococcus aureus, Streptococci haemolyticus, Pneumococci, Pseudomanoas aeruginosa, Haemophilus influenzae.
  • the viral infection is an infection with human influenza
  • the bacterial infection is preferably an infection with one or more of Staphylococcus aureus, Streptococci haemolyticus, Pneumococci, Pseudomanoas aeruginosa, and Haemophilus influenzae.
  • Mycoplasma pneumoniae is a common cause of respiratory disease and co-infections with influenza virus and respiratory syncytial virus have been reported, as has the fact that M- pneumoniae can superinfect during an influenza outbreak.
  • the viral infection is an infection with influenza
  • the bacterial infection is preferably an infection with Mycoplasma pneumoniae.
  • Also provided is a method of preventing or treating a viral infection comprising administering tiamulin or a functional derivative, metabolite, ester or salt thereof, or a pharmaceutical composition comprising tiamulin or a functional derivative, metabolite, ester or salt thereof, to a subject having a viral infection.
  • the method may also be used for simultaneously treating or preventing a bacterial infection.
  • a pharmaceutical composition to be administered in the method of the invention comprises tiamulin or a functional derivative, metabolite, ester or salt thereof with any pharmaceutically acceptable carrier, adjuvant or vehicle.
  • Pharmaceutically acceptable carriers, adjuvants and vehicles that may be used in the pharmaceutical composition include, but are not limited to, ion exchangers, alumina, aluminium stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycerine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose- based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene- polyoxypropylene-block polymers,
  • the pharmaceutical composition may be administered orally, parenterally, by inhalation spray, rectally, nasally, buccally, vaginally, topically, transdermally or via an implanted reservoir.
  • the pharmaceutical compositions of this invention may contain any conventional non-toxic pharmaceutically-acceptable carriers, adjuvants or vehicles.
  • parenteral as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, intra-articular, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques.
  • the pharmaceutical composition may be in the form of a sterile injectable preparation, for example, as a sterile injectable aqueous or oleaginous suspension.
  • This suspension may be formulated according to techniques known in the art using suitable dispersing or wetting agents (such as, for example, Tween 80) and suspending agents.
  • the sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally- acceptable diluent or solvent, for example, as a solution in 1,3-butanediol.
  • suitable vehicles and solvents that may be employed are mannitol, water, Ringer's solution and isotonic sodium chloride solution.
  • sterile, fixed oils are conventionally employed as a solvent or suspending medium.
  • any bland fixed oil may be employed including synthetic mono- or diglycerides.
  • Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions.
  • These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant such as Ph. HeIv or a similar alcohol.
  • the pharmaceutical composition may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, and aqueous suspensions and solutions.
  • carriers which are commonly used include lactose and corn starch.
  • Lubricating agents such as magnesium stearate, are also typically added.
  • useful diluents include lactose and dried corn starch.
  • aqueous suspensions are administered orally, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening and/or flavouring and/or colouring agents may be added.
  • compositions may also be administered in the form of suppositories for rectal administration.
  • suppositories for rectal administration.
  • These compositions can be prepared by mixing a compound of this invention with a suitable non-irritating excipient which is solid at room temperature but liquid at the rectal temperature and therefore will melt in the rectum to release the active components.
  • suitable non-irritating excipient include, but are not limited to, cocoa butter, beeswax and polyethylene glycols.
  • compositions may be administered by nasal aerosol or inhalation.
  • Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other solubilising or dispersing agents known in the art.
  • the subject may be any subject having a viral infection.
  • the subject may be a human or an animal.
  • the host is an animal, especially a livestock animal such as a cow, horse or pig. It is particularly preferred that the host is a pig.
  • the host is preferably a human.
  • Figure 1 shows the inhibition of influenza A virus infection by tiamulin
  • Figure 2 shows the inhibition of type 1 (European) PRRSV infection by tiamulin
  • Figure 3 shows the inhibition of type 2 (US) PRRSV infection by tiamulin
  • Figure 4 shows tiamulin raises endosomal pH
  • Figure 5 compares the effect of tiamulin and valnemulin on type 1 PRRSV; and Figure 6 compares the effect of tiamulin and valnemulin on influenza.
  • MDCK cells were pretreated with 1 ⁇ g/ml tiamulin for 4 hours prior to infection. Cells were then infected with human influenza strains PR8 (HlNl) and Udorn (H3N2) or equine influenza A strain Miami (H3N8) at multiplicity of infection of 10. Cells were harvested 4 hours post infection by fixation with formal saline in preparation for immunofluorescence.
  • Virus infection was detected by indirect immunofluorescence to the influenza virus nucleoprotein.
  • MAl 04 were pretreated with various concentrations of tiamulin for 4 hours prior to infection.
  • Cells were then infected with DV strain of PRRSV at multiplicity of infection of 10.
  • Cells were harvested 24 hours post infection by fixation with formal saline in preparation for immunofluorescence.
  • Virus infection was detected by indirect immunofluorescence to the PRRSV N protein.
  • MAl 04 were pretreated with various concentrations of tiamulin for 4 hours prior to infection.
  • Cells were then infected with VR2332 strain of PRRSV at multiplicity of infection of 10.
  • Cells were harvested 24 hours post infection by fixation with formal saline in preparation for immunofluorescence.
  • Virus infection was detected by indirect immunofluorescence to the PRRSV N protein.
  • MAl 04 or MDCK cells were pretreated with various concentrations of tiamulin for 4 hours. After this time the cells were incubated with 20 ⁇ M acridine orange for 1 minute. Cells were washed, mounted for immunofluorescence and then viewed immediately. The number of endosomes for 20 cells was counted and the average number plotted.
  • Asfarviridae Asfarvirus African swine fever virus Pig Bunyaviridae Hantavirus Puumala virus man Circoviridae Circovirus porcine circovirus 2 Pig Coronaviridae Corona virus infectious bronchitis virus fowl transmissible gastroenteritis virus (TGEV) pig
  • Orthomyxoviridae Isavirus salmon infectious anaemia virus salmon

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Abstract

L’invention porte sur un médicament antiviral fabriqué à l’aide d’un antibiotique.
PCT/GB2009/000548 2008-02-28 2009-02-27 Utilisation de la tiamuline en tant qu’agent antiviral Ceased WO2009106839A1 (fr)

Applications Claiming Priority (2)

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GB0803707.9 2008-02-28
GB0803707A GB0803707D0 (en) 2008-02-28 2008-02-28 Antiviral agent

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WO2009106839A1 true WO2009106839A1 (fr) 2009-09-03

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Cited By (7)

* Cited by examiner, † Cited by third party
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WO2016063134A1 (fr) 2014-10-24 2016-04-28 Redhill Biopharma Ltd. Thérapie pour l'inhibition de la réplication d'un virus à arn simple brin
CN113143923A (zh) * 2021-05-25 2021-07-23 湖北工业大学 Retapamulin化合物在制备抗EV71病毒药物中的应用
AT523646B1 (de) * 2020-07-21 2021-10-15 Gerd Dr Ascher Pharmazeutische Verbindungen, ihre Anwendung alleine oder in Kombination, zur Prophylaxe und lokalen Initial-Therapie bei bakteriellen und viralen Infektionen, insbesondere Coronaviren
WO2021209173A1 (fr) 2020-04-17 2021-10-21 Nabriva Therapeutics GmbH Nouvelle utilisation thérapeutique de pleuromutilines
WO2021209596A1 (fr) 2020-04-17 2021-10-21 Nabriva Therapeutics GmbH Utilisation thérapeutique de pleuromutilines
WO2021209174A1 (fr) 2020-04-17 2021-10-21 Nabriva Therapeutics GmbH Utilisation thérapeutique de pleuromutilines
WO2023152115A1 (fr) * 2022-02-09 2023-08-17 Nabriva Therapeutics GmbH Léfamuline et ses dérivés pour utilisation dans le traitement contre une bactérie en forme de spirale

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US12370206B2 (en) 2014-10-24 2025-07-29 Redhill Biopharma Ltd. Therapy for inhibition of single-stranded RNA virus replication
CN107106525A (zh) * 2014-10-24 2017-08-29 红山生物医药有限公司 用于抑制单链rna病毒复制的治疗
JP2017531673A (ja) * 2014-10-24 2017-10-26 レッド ヒル バイオファーマ リミテッドＲｅｄＨｉｌｌ Ｂｉｏｐｈａｒｍａ Ｌｔｄ． １本鎖ｒｎａウイルス複製を阻害するための治療
EP3209290A4 (fr) * 2014-10-24 2018-11-14 Redhill Biopharma Ltd. Thérapie pour l'inhibition de la réplication d'un virus à arn simple brin
US10543222B2 (en) 2014-10-24 2020-01-28 Redhill Biopharma Ltd. Therapy for inhibition of single-stranded RNA virus replication
CN107106525B (zh) * 2014-10-24 2021-03-19 红山生物医药有限公司 用于抑制单链rna病毒复制的治疗
US11786541B2 (en) 2014-10-24 2023-10-17 Redhill Biopharma Ltd. Inhibitor of sphingosine kinase 2 for treating Ebola
WO2016063134A1 (fr) 2014-10-24 2016-04-28 Redhill Biopharma Ltd. Thérapie pour l'inhibition de la réplication d'un virus à arn simple brin
CN115413238A (zh) * 2020-04-17 2022-11-29 纳布里瓦治疗有限责任公司 截短侧耳素类化合物的治疗用途
WO2021209173A1 (fr) 2020-04-17 2021-10-21 Nabriva Therapeutics GmbH Nouvelle utilisation thérapeutique de pleuromutilines
WO2021209596A1 (fr) 2020-04-17 2021-10-21 Nabriva Therapeutics GmbH Utilisation thérapeutique de pleuromutilines
WO2021209174A1 (fr) 2020-04-17 2021-10-21 Nabriva Therapeutics GmbH Utilisation thérapeutique de pleuromutilines
CN115443131A (zh) * 2020-04-17 2022-12-06 纳布里瓦治疗有限责任公司 截短侧耳素类化合物的治疗用途
AT523646A4 (de) * 2020-07-21 2021-10-15 Gerd Dr Ascher Pharmazeutische Verbindungen, ihre Anwendung alleine oder in Kombination, zur Prophylaxe und lokalen Initial-Therapie bei bakteriellen und viralen Infektionen, insbesondere Coronaviren
WO2022016202A1 (fr) * 2020-07-21 2022-01-27 Gerd Ascher Dérivé de la pleuromutiline et/ou ivermectine, pour le traitement des infections, en particulier à coronavirus
AT523646B1 (de) * 2020-07-21 2021-10-15 Gerd Dr Ascher Pharmazeutische Verbindungen, ihre Anwendung alleine oder in Kombination, zur Prophylaxe und lokalen Initial-Therapie bei bakteriellen und viralen Infektionen, insbesondere Coronaviren
CN113143923B (zh) * 2021-05-25 2023-04-25 湖北工业大学 Retapamulin化合物在制备抗EV71病毒药物中的应用
CN113143923A (zh) * 2021-05-25 2021-07-23 湖北工业大学 Retapamulin化合物在制备抗EV71病毒药物中的应用
WO2023152115A1 (fr) * 2022-02-09 2023-08-17 Nabriva Therapeutics GmbH Léfamuline et ses dérivés pour utilisation dans le traitement contre une bactérie en forme de spirale

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