Treatment of coronavirus infections

Abstract

The invention relates to dextran sulfate, or a pharmaceutically acceptable salt thereof, for use in treatment of a coronavirus infection or infectious disease and infections caused by other HSPG binding pathogens. The invention also relates to treatment of inflammatory diseases, such as ARDS and SIRS, which may occur in connection with such infections.

1 - 21 . (canceled) 
     
     
         22 . A method for preventing, inhibiting or treating a coronavirus infection or infectious disease in a subject, the method comprises administering dextran sulfate, or a pharmaceutically acceptable salt thereof, having an average molecular weight equal to or below 10,000 Da to the subject to prevent, inhibit or treat a coronavirus infection or infectious disease. 
     
     
         23 . The method according to  claim 22 , wherein the coronavirus infectious disease is selected from the group consisting of Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS) and Coronavirus disease 2019 (COVID-19). 
     
     
         24 . The method according to  claim 23 , wherein the coronavirus infectious disease is COVID-19. 
     
     
         25 . The method according to  claim 22 , wherein the coronavirus infection is selected from the group consisting of a coronavirus infection caused by a coronavirus selected from the group consisting of Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 
     
     
         26 . The method according to  claim 25 , wherein the coronavirus infection is caused by SARS-CoV-2. 
     
     
         27 . The method according to  claim 22 , wherein the average molecular weight is within a range of from 2000 to 10,000 Da. 
     
     
         28 . The method according to  claim 27 , wherein the average molecular weight is within a range of from 3000 to 10,000 Da. 
     
     
         29 . The method according to  claim 28 , wherein the average molecular weight is within a range of from 3500 to 9500 Da. 
     
     
         30 . The method according to  claim 29 , wherein the average molecular weight is within a range of from 4500 to 7500 Da. 
     
     
         31 . The method according to  claim 30 , wherein the average molecular weight is within a range of from 4500 to 5500 Da. 
     
     
         32 . The method according to  claim 22 , wherein the dextran sulfate, or the pharmaceutically acceptable salt thereof, has an average sulfur content in a range of from 15 to 20%. 
     
     
         33 . The method according to  claim 22 , wherein the dextran sulfate, or the pharmaceutically acceptable salt thereof, has a number average molecular weight (Mn) as measured by nuclear magnetic resonance (NMR) spectroscopy within a range of from 1850 to 3500 Da. 
     
     
         34 . The method according to  claim 33 , wherein the dextran sulfate, or the pharmaceutically acceptable salt thereof, has a Mn as measured by NMR spectroscopy within a range of from 1850 to 2500 Da. 
     
     
         35 . The method according to  claim 34 , wherein the dextran sulfate, or the pharmaceutically acceptable salt thereof, has a Mn as measured by NMR spectroscopy within a range of from 1850 to 2300 Da. 
     
     
         36 . The method according to  claim 35 , wherein the dextran sulfate, or the pharmaceutically acceptable salt thereof, has a Mn as measured by NMR spectroscopy within a range of from 1850 to 2000 Da. 
     
     
         37 . The method according to  claim 22 , wherein the dextran sulfate, or the pharmaceutically acceptable salt thereof, has an average sulfate number per glucose unit within a range of from 2.5 to 3.0. 
     
     
         38 . The method according to  claim 37 , wherein the dextran sulfate, or the pharmaceutically acceptable salt thereof, has an average sulfate number per glucose unit within a range of from 2.5 to 2.8. 
     
     
         39 . The method according to  claim 38 , wherein the dextran sulfate, or the pharmaceutically acceptable salt thereof, has an average sulfate number per glucose unit within a range of from 2.6 to 2.7. 
     
     
         40 . The method according to  claim 22 , wherein the dextran sulfate, or the pharmaceutically acceptable salt thereof, has on average 5.1 glucose units and an average sulfate number per glucose unit of 2.6 to 2.7. 
     
     
         41 . The method according to  claim 22 , wherein administering dextran sulfate, or the pharmaceutically acceptable salt thereof, comprises systemically administering dextran sulfate, or the pharmaceutically acceptable salt thereof, to the subject. 
     
     
         42 . The method according to  claim 41 , wherein systemically administering dextran sulfate, or the pharmaceutically acceptable salt thereof, comprises subcutaneously administering dextran sulfate, or the pharmaceutically acceptable salt thereof, to the subject. 
     
     
         43 . The method according to  claim 41 , wherein systemically administering dextran sulfate, or the pharmaceutically acceptable salt thereof, comprises intravenously administering dextran sulfate, or the pharmaceutically acceptable salt thereof, to the subject. 
     
     
         44 . The method according to  claim 22 , wherein administering dextran sulfate, or the pharmaceutically acceptable salt thereof, comprises administering an aqueous injection solution comprising the dextran sulfate, or the pharmaceutically acceptable salt thereof, to the subject. 
     
     
         45 . The method according to  claim 22 , wherein the pharmaceutically acceptable salt thereof is a sodium salt of dextran sulfate. 
     
     
         46 . A method for preventing, inhibiting or treating an inflammatory disease in a subject, the method comprises administering dextran sulfate, or a pharmaceutically acceptable salt thereof, having an average molecular weight equal to or below 10,000 Da to the subject to prevent, inhibit or treat the inflammatory disease, wherein the inflammatory disease is selected from the group consisting of acute respiratory distress syndrome (ARDS) and systemic inflammatory response syndrome (SIRS). 
     
     
         47 . A method for preventing, inhibiting or treating an infection or infectious disease in a subject, the method comprises administering dextran sulfate, or a pharmaceutically acceptable salt thereof, having an average molecular weight equal to or below 10,000 Da to the subject to prevent, inhibit or treat an infection or infectious disease caused by a pathogen capable of binding to cell surface heparan sulfate proteoglycans (HSPG). 
     
     
         48 . The method according to  claim 47 , wherein the pathogen is capable of binding to HSPG to facilitate initial cellular attachment and/or subsequent cellular entry. 
     
     
         49 . The method according to  claim 47 , wherein the pathogen is capable of binding to the heparan sulfate part of HSPG.