In silico discovery of effective antimicrobials

Patent metadata

Field	Value
Publication number	US-12469580-B2
Application number	US-202017641704-A
Country	US
Kind code	B2
Filing date	Sep 9, 2020
Priority date	Sep 10, 2019
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

The present disclosure relates to antimicrobial compositions, particularly to antibiotic compositions; to methods for identification of antimicrobial compositions involving in silico prediction of antimicrobial activity; and to use of antimicrobial compositions and methods.

First claim

We claim:

1 . A pharmaceutical composition for treating a microbial infection in a subject comprising a therapeutically effective amount of:

5-[(5-nitro-1,3-thiazol-2-yl)sulfanyl]-1,3,4-thiadiazol-2-amine,
or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier.

2 . The pharmaceutical composition of claim 1 , wherein the microbial infection is resistant to or tolerant to one or more antimicrobial agents.

3 . The pharmaceutical composition of claim 1 , wherein the microbial infection is a bacterial infection.

4 . The pharmaceutical composition of claim 1 , wherein the microbial infection is caused by:
an Acinetobacter spp., Acinetobacter baumannii, Escherichia spp., Escherichia coli, Campylobacter, Neisseria gonorrhoeae, Providencia spp., Enterobacter spp., Enterobacter cloacae, Enterobacter aerogenes , carbpanem-resistant Enterobacteriaceae, Klebsiella spp. Klebsiella pneumoniae, Salmonella, Pasteurella spp., Proteus spp., Proteus mirabilis, Serratia spp., Serratia marcescens, Citrobacter spp., Acinetobacter, Morganella morganii, Pseudomonas aeruginosa, Burkholderia pseudomallei, Burkholderia cenocepacia, Helicobacter pylori, Treponema pallidum, Hemophilus influenza, Clostridium difficile, Enterococcus, E. faecalis, E. faecium, E. casseliflavus, E. gallinarum, E. raffinosus , vanomycin-resistant Enteroccocus (VRE), Mycobacterium tuberculosis, Mycobacterium avium complex, Mycobacterium intracellulare , and Mycobacterium avium, Mycobacterium smegmatis, Mycoplasms genitalium, Staphylococcus aureus , methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Streptococcus pneumoniae, Mycobaterium leprae, Listeria spp., and/or Listeria monocytogenes bacteria; or an Aspergillus, Blastomyces, Candida, Candida auris, Coccidioides, Candida neoformans, Candida gattii, Histoplasma, Mucormycetes, Mycetoma, Pneumocytsis jirovencii, Trichophyton, Microsporum, Epidermophyton, Sporothrix, Paracoccidioidomycosis, Talaromycosis , and/or Cryptococcus fungus.

5 . A method of treating a microbial infection comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 1

6 . The method of claim 5 , wherein the microbial infection is resistant to or tolerant to one or more antimicrobial agents.

7 . The method of claim 5 , wherein the microbial infection is a bacterial infection.

8 . The method of claim 5 , wherein the microbial infection is caused by:
an Acinetobacter spp., Acinetobacter baumannii, Escherichia spp., Escherichia coli, Campylobacter, Neisseria gonorrhoeae, Providencia spp., Enterobacter spp., Enterobacter cloacae, Enterobacter aerogenes , carbpanem-resistant Enterobacteriaceae, Klebsiella spp. Klebsiella pneumoniae, Salmonella, Pasteurella spp., Proteus spp., Proteus mirabilis, Serratia spp. Serratia marcescens, Citrobacter spp., Acinetobacter, Morganella morganii, Pseudomonas aeruginosa, Burkholderia pseudomallei, Burkholderia cenocepacia, Helicobacter pylori, Treponema pallidum Hemophilus influenza, Clostridium difficile, Enterococcus, E. faecalis, E. faecium, E. casseliflavus, E. gallinarum, E. raffinosus , vanomycin-resistant Enteroccocus (VRE), Mycobacterium tuberculosis, Mycobacterium avium complex Mycobacterium intracellulare , and Mycobacterium avium, Mycobacterium smegmatis, Mycoplasms genitalium, Staphylococcus aureus , methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Streptococcus pneumoniae, Mycobaterium leprae, Listeria spp., and/or Listeria monocytogenes bacteria; or an Aspergillus, Blastomyces, Candida, Candida auris, Coccidioides, Candida neoformans, Candida gattii, Histoplasma, Mucormycetes, Mycetoma, Pneumocytsis jirovencii, Trichophyton, Microsporum, Epidermophyton, Sporothrix, Paracoccidioidomycosis, Talaromycosis , and/or Cryptococcus fungus.

9 . The pharmaceutical composition of claim 1 , wherein the microbial infection is an antibiotic-resistant bacterial infection or an antibiotic-tolerant bacterial infection.

10 . The pharmaceutical composition of claim 1 , wherein the microbial infection is caused by a bacteria selected from the group consisting of Clostridioides difficile , pan-resistant Acinetobacter baumannii , carbapenem-resistant Enterobacteriaceae (CRE) species, Mycobacterium tuberculosis , and Methicillin-resistant Staphylococcus aureus (MRSA).

11 . The pharmaceutical composition of claim 1 , formulated for oral administration, intravenous administration, intramuscular administration, intraperitoneal administration, intracerobrospinal administration, intracranial administration, intraspinal administration, subcutaneous administration, intraarticular administration, intrasynovial administration, intrathecal administration, topical administration, or administration via inhalation.

12 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier comprises a liquid filler, a solid filler, a diluent, an excipient, a solvent, or an encapsulating material.

13 . The pharmaceutical composition of claim 1 in the form of a pharmaceutically acceptable salt.

14 . The pharmaceutical composition of claim 1 comprising a therapeutically effective amount of 5-[(5-nitro-1,3-thiazol-2-yl)sulfanyl]-1,3,4-thiadiazol-2-amine and a pharmaceutically acceptable carrier.

15 . A pharmaceutical composition for treating a bacterial infection in a subject comprising a therapeutically effective amount of:

5-[(5-nitro-1,3-thiazol-2-yl)sulfanyl]-1,3,4-thiadiazol-2-amine,
or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier.

16 . The pharmaceutical composition of claim 15 , wherein the bacterial infection is resistant to one or more antibiotic agents.

17 . The pharmaceutical composition of claim 15 , wherein the bacterial infection is caused by an Acinetobacter spp., Acinetobacter baumannii, Escherichia spp., Escherichia coli, Campylobacter, Neisseria gonorrhoeae, Providencia spp., Enterobacter spp., Enterobacter cloacae, Enterobacter aerogenes , carbpanem-resistant Enterobacteriaceae, Klebsiella spp., Klebsiella pneumoniae, Salmonella, Pasteurella spp., Proteus spp., Proteus mirabilis, Serratia spp., Serratia marcescens, Citrobacter spp., Acinetobacter, Morganella morganii, Pseudomonas aeruginosa, Burkholderia pseudomallei, Burkholderia cenocepacia, Helicobacter pylori, Treponema pallidum, Hemophilus influenza, Clostridium difficile, Enterococcus, E. faecalis, E. faecium, E. casseliflavus, E. gallinarum, E. raffinosus , vanomycin-resistant Enteroccocus (VRE), Mycobacterium tuberculosis, Mycobacterium avium complex, Mycobacterium intracellulare, Mycobacterium avium, Mycobacterium smegmatis, Mycoplasms genitalium, Staphylococcus aureus , methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Streptococcus pneumoniae, Mycobaterium leprae, Listeria spp., and/or Listeria monocytogenes bacteria.

18 . A pharmaceutical composition for treating a fungal infection in a subject comprising a therapeutically effective amount of:

Assignees

• Massachusetts Inst Of Techology
• Broad Inst Inc

Inventors

• Collins James
• Barzilay Regina
• Stokes Jonathan
• Andrews Ian
• Collins Daniel

Classifications

• G06N3/126

  Evolutionary algorithms, e.g. genetic algorithms or genetic programming · CPC title

• A61K31/655

  Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds · CPC title

• A61K31/433

  Thidiazoles · CPC title

• G16B40/20

  Supervised data analysis · CPC title

• G16B35/20

  Screening of libraries · CPC title