Cationic Steroid Antimicrobial Compositions and Methods of Use

Abstract

The invention provides methods for decreasing or inhibiting herpesviridae (HV) infection or pathogenesis of a cell in vitro, ex vivo or in vivo, a symptom or pathology associated with a herpesviridae (HV) infection or pathogenesis in vitro, ex vivo or in vivo, or an adverse side effect of herpesviridae (HV) infection or pathogenesis in vitro, ex vivo or in vivo. In one embodiment, a method of the invention includes treating a subject with an invention compound (e.g., cationic steroid antimicrobial or CSA).

1 . A method for providing a subject with protection against a herpesviridae (HV) infection or pathogenesis, comprising administering a sufficient amount of cationic steroid antimicrobial (CSA) to provide the subject with protection against herpesviridae (HV) infection or pathogenesis. 
     
     
         2 . A method for treating a subject in need of treatment for herpesviridae (HV) infection or pathogenesis, comprising administering a sufficient amount of cationic steroid antimicrobial (CSA) to treat the subject for the herpesviridae (HV) infection or pathogenesis. 
     
     
         3 . A method for decreasing susceptibility or inhibiting herpesviridae (HV) reactivation from latency in a subject, comprising administering a sufficient amount of cationic steroid antimicrobial (CSA) to decrease susceptibility or inhibit herpesviridae (HV) reactivation from latency in the subject. 
     
     
         4 . The method of  claim 1 , wherein the CSA is administered prior to, concurrently with, or following infection of the subject with HV, exposure to or contact of the subject with HV, or reactivation of HV. 
     
     
         5 . The method of  claim 1 , wherein the CSA is administered prior to, concurrently with, or following development of a symptom or pathology of acute or chronic HV infection, or reactivation of HV from latency. 
     
     
         6 . The method of  claim 1 , wherein the CSA is administered to a biological fluid, an immune cell or tissue, mucosal cell or tissue, neural cell or tissue, or epithelial cell or tissue. 
     
     
         7 . The method of  claim 1 , wherein the HV is present in a biological fluid, cell, tissue or organ. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the HV is present in an immune cell tissue or organ, mucosal cell, tissue or organ, neural cell, tissue or organ, or epithelial cell, tissue or organ. 
     
     
         11 - 14 . (canceled) 
     
     
         15 . The method of  claim 1 , wherein the HV comprises an alpha-herpesvirus, beta-herpesvirus or gamma-herpesvirus. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . The method of any of  claim 1 , wherein the CSA is selected from CSA-7, CSA-8, CSA-10, CSA-11, CSA-13, CSA-15, CSA-17, CSA-21, CSA-25, CSA-26, CSA-31, CSA-46, CSA-54 and CSA-59, as set forth in  FIG. 10 . 
     
     
         19 - 24 . (canceled) 
     
     
         25 . The method of  claim 1 , wherein the CSA has a shorter tether length between the steroid scaffold and the amine groups at positions C3, C7 and C12, relative to the tether length of CSA-7, CSA-8, CSA-10, CSA-11, CSA-13, CSA-15, CSA-17, CSA-21, CSA-25, CSA-26, CSA-31, CSA-46, CSA-54 or CSA-59, as set forth in  FIG. 10 . 
     
     
         26 . The method of  claim 1 , wherein the CSA comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         27 . The method of  claim 1 , wherein the CSA comprises a sterile formulation. 
     
     
         28 . The method of  claim 1 , wherein the CSA comprises a composition comprising one or more additional CSAs or biologically active ingredients. 
     
     
         29 - 46 . (canceled) 
     
     
         47 . The method of  claim 1 , further comprising administering to the subject an additional CSA or treatment. 
     
     
         48 - 52 . (canceled) 
     
     
         53 . The method of  claim 47 , wherein the additional treatment comprises an antibody that binds to an HV protein. 
     
     
         54 . The method of  claim 53 , wherein the HV protein is selected from: envelope protein, tegument protein, capsid protein, core protein and polymerase. 
     
     
         55 . The method of  claim 54 , wherein the envelope protein comprises glycoprotein gp42, gp350, gpK8.1A, B, C, D, E, H, L (gB, gC, gD, gE, gH, gL). 
     
     
         56 . The method of  claim 54 , wherein the tegument protein comprises: UL17, UL36, UL37, UL48, UL49, US11, UL11, UL14, UL16, UL21, UL41, UL46, UL47, VP13/14, VP16 and VP22. 
     
     
         57 - 59 . (canceled) 
     
     
         60 . A method for decreasing or inhibiting herpesviridae (HV) infection of a cell or herpesviridae (HV) reactivation from latency, in vitro or in vivo, comprising administering a composition comprising a sufficient amount of cationic steroid antimicrobial (CSA) to inhibit herpesviridae (HV) infection of the cell. 
     
     
         61 - 65 . (canceled) 
     
     
         66 . A method for reducing, decreasing, inhibiting, ameliorating or preventing onset, severity, duration, progression, frequency or probability of one or more symptoms or pathologies associated with or caused by herpesviridae (HV) infection or pathogenesis, or reactivation of herpesviridae (HV) from latency, in a subject, comprising administering a sufficient amount of CSA-7, CSA-8, CSA-10, CSA-11, CSA-13, CSA-15, CSA-17, CSA-21, CSA-25, CSA-26, CSA-31, CSA-46, CSA-54 and CSA-59, as set forth in  FIG. 10 , to decrease, inhibit, ameliorate or prevent onset, severity, duration, progression, frequency or probability of one or more symptoms or pathologies associated with or caused by herpesviridae (HV) infection or pathogenesis, or reactivation of herpesviridae (HV) from latency in the subject. 
     
     
         67 . (canceled) 
     
     
         68 . A method for identifying a candidate agent for treating a subject for an HV infection or pathogenesis, or reactivation from latency, comprising:
 a) providing a test agent, said test agent comprising a cationic steroid antimicrobial (CSA);   b) contacting said test agent with HV and ascertaining whether the test agent inhibits HV infection or pathogenesis, or reactivation from latency, wherein a test agent identified as inhibiting HV infection or pathogenesis or reactivation from latency is a candidate agent for treating a subject for HV infection or pathogenesis.   
     
     
         69 . A method for identifying a candidate agent for decreasing susceptibility or inhibiting HV reactivation from latency, comprising:
 a) providing a test agent, said test agent comprising a cationic steroid antimicrobial (CSA);   b) contacting said test agent with HV and ascertaining whether the test agent decreases susceptibility or inhibits HV reactivation from latency, wherein a test agent identified as decreasing susceptibility or inhibiting HV reactivation from latency is a candidate agent for decreasing susceptibility or inhibiting HV reactivation from latency.   
     
     
         70 . A method for identifying a candidate agent for decreasing, inhibiting, ameliorating or preventing onset, severity, duration, progression, frequency or probability of one or more symptoms or pathologies caused by or associated with HV infection or pathogenesis or reactivation from latency comprising:
 a) providing a test agent, said test agent comprising a cationic steroid antimicrobial (CSA);   b) administering said test agent to a subject infected with or exposed to HV and ascertaining whether the test agent decreases, inhibits, ameliorates or prevents onset, severity, duration, progression, frequency or probability of one or more symptoms or pathologies associated with or caused by HV infection or pathogenesis, or reactivation from latency, wherein a test agent identified is a candidate agent for decreasing, inhibiting, ameliorating or preventing onset, severity, duration, progression, frequency or probability of one or more symptoms or pathologies associated with or caused by HV infection or pathogenesis or reactivation from latency.   
     
     
         71 - 72 . (canceled)