WO2022078536A1 - Combinaison de substances pour l'inhibition de protéases à cystéine virales - Google Patents

Combinaison de substances pour l'inhibition de protéases à cystéine virales Download PDF

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Publication number
WO2022078536A1
WO2022078536A1 PCT/DE2021/000142 DE2021000142W WO2022078536A1 WO 2022078536 A1 WO2022078536 A1 WO 2022078536A1 DE 2021000142 W DE2021000142 W DE 2021000142W WO 2022078536 A1 WO2022078536 A1 WO 2022078536A1
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WO
WIPO (PCT)
Prior art keywords
cov
viral
bat
substance combination
hcov
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PCT/DE2021/000142
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German (de)
English (en)
Inventor
Monika Aparecida CORONADO
Raphael Josef EBERLE
Dieter Willbold
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Forschungszentrum Jülich GmbH
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Publication of WO2022078536A1 publication Critical patent/WO2022078536A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines

Definitions

  • FIG. 4 shows a number of fluorescence spectra of SARS-CoV-2 3CL per , which were recorded under the influence of different substance concentrations of suramin (Graph A) and quinacrine (Graph C).
  • FIG. 4 also shows binding saturation curves created for this purpose in order to determine the respective dissociation constant KD.
  • the abscissas (X axes) of the fluorescence spectra indicate the wavelengths in nm at which the fluorescence intensities were measured.
  • the arrow running from top to bottom in graphs A and C in FIG. 4 indicates the associated added substance concentration (0 to 48 pmol/L) of the active substance quinacrine/suramin for the individual fluorescence spectra recorded.
  • the ordinates (Y-axes) indicate the respectively measured fluorescence intensities in relative fluorescence units.
  • the arrows marked with an asterisk, which run parallel to the abscissa in graphs A and C, indicate the shift in the fluorescence maximum caused by the active substance.
  • FIG. 4 Graph C Fluorescence spectrum of SARS-CoV-2 3CL pro under the influence of quinacrine titration. Quinacrine causes a “blue edge excitation shift” of the visible Trp (*).
  • FIG. 4 Graph D A KD value could be determined with the aid of a binding saturation curve and a modified Hill equation SARS-CoV-2 3CL per -quinacrine interaction.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une combinaison des substances suramine et quinacrine pour inhiber les protéases à cystéine virales, plus particulièrement pour inhiber les protéases 3CL virales, et l'utilisation de ladite combinaison de substances pour produire un inhibiteur pour les protéases à cystéine virales, plus particulièrement les protéases 3CL. L'invention concerne également une combinaison de substances pour le traitement d'une infection virale dans un organisme, plus particulièrement pour le traitement d'une infection par des virus de la famille des coronaviridae, et la combinaison de substances en tant que médicament dans le traitement d'infections virales, plus particulièrement dans le traitement d'une infection par des virus de la famille des coronaviridae.
PCT/DE2021/000142 2020-10-14 2021-08-27 Combinaison de substances pour l'inhibition de protéases à cystéine virales WO2022078536A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102020006305.5 2020-10-14
DE102020006305.5A DE102020006305A1 (de) 2020-10-14 2020-10-14 Stoffkombination zur Inhibierung von viralen Cysteinproteasen

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WO2022078536A1 true WO2022078536A1 (fr) 2022-04-21

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DE (1) DE102020006305A1 (fr)
WO (1) WO2022078536A1 (fr)

Non-Patent Citations (20)

* Cited by examiner, † Cited by third party
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