Saint Louis University

The City University of New York

The United States Government As Represented by the Department of Veterans Affairs

Maureen J Donlin

John Edwin Tavis

Ryan Murelli

Rajeev Aurora

Marvin Jay Meyers

Bahaa Elgendy

Cari Orth

Feng Cao

In one aspect, the present disclosure provides methods of treating a bacterial infection using an inhibitor of the nucleotidyltransferase superfamily enzyme. In some embodiments, the compounds have one of the following formulas (I), (II), (III), or (IV) wherein R, R, and Rare as defined herein or a pharmaceutically acceptable salt thereof. The compounds may be used to treat a bacterial infection including an infection of, andspecies.

Inhibitors of nucleotidyltransferase superfamily enzymes as antibiotics

The present disclosure provides compounds of the formula (I), (II), (III), wherein the variables are as defined herein for use in the treatment of fungal infections. In some embodiments, the fungal infection is an infection offungus. Also provided herein are compositions comprising a compound of formula I, II, or III and a second anti-fungal agent. 

Anti-fungal compounds

Methods of identifying targets for designing a therapeutic agent are disclosed. These methods comprise: determining an amino acid sequence of one or more polypeptides of each isolate of a plurality of isolates of a biological system; identifying covariance pairs of amino acid residues; establishing a network comprising the covariance pairs; and identifying one or more hub residue positions, wherein a hub residue position comprises a target for designing a therapeutic agent if the hub residue position has a rank order in the 40percentile or greater. In other aspects, methods are disclosed for selecting a therapy for an infectious disorder. In various configurations, these methods comprise: determining amino acids occupying a plurality of diagnostic amino acid residue positions comprised by one or more polypeptides encoded by an infectious agent infecting a subject; and assigning the infectious agent infecting the subject to one covariance network selected from a plurality of covariance networks, wherein each network comprises a unique rank order of hubs with respect to the other networks, and whereby the therapy is selected on the basis of the covariance network assignment.

Sequence covariance networks, methods and uses therefor

Growing community of inventors

Kirkwood, MO, United States of America

Maureen J Donlin