Treatment of human coronavirus infections using alpha-glucosidase glycoprotein processing inhibitors

1 . A method for treating human coronavirus infection or a symptom, in a human subject, wherein the coronavirus is SARS-COV-2 or a variant thereof, said method comprising administering an effective amount of an alpha-glucosidase glycoprotein processing inhibitor to the human subject, wherein said alpha-glucosidase glycoprotein processing inhibitor comprises castanospermine or a pharmaceutically acceptable salt or prodrug thereof, and

wherein the prodrug of castanospermine has the following structure of Formula (I):

wherein R 3 is (C 1 -C 14 ) acyl, (C 1 -C 14 ) alkenylacyl, (C 3 -C 8 ) cycloalkylacyl, (C 1 -C 14 ) haloalkylacyl (C 1 -C 8 ) alkoxyacyl, or (C 6 -C 10 ) arylacyl.

2 . The method of claim 1 , further comprising, prior to said administering, identifying the subject as having the coronavirus infection, wherein said identifying comprises assaying a biological sample obtained from the subject for the presence of coronavirus nucleic acid or coronavirus protein.

3 . The method of claim 1 , wherein the prodrug comprises celgosivir (6-O-butanoyl castanospermine) or a pharmaceutically acceptable salt thereof.

4 . The method of 1 , wherein said method comprises:

(a) determining that the human subject is infected with a coronavirus;

(b) administering to the human subject at least one initial dose of about 15 mg to about 600 mg of a compound of Formula (I); and

(c) administering to the human subject a plurality of subsequent doses of about 15 mg to about 400 mg of a compound of Formula (I) or a pharmaceutically acceptable salt thereof,

wherein not more than 600 mg of a compound of Formula (I) is administered per day.

5 . The method of claim 4 , wherein the compound of Formula (I) is a compound of Formula (II), or a pharmaceutically acceptable salt thereof:

6 . The method of claim 4 , wherein the compound of Formula (I) is converted to castanospermine after administration to the human subject, and wherein a steady state Cmin serum or plasma concentration of between about 0.4 and about 2.0 microgram/ml of castanospermine is attained in the human subject after administrations of initial and subsequent doses.

7 . The method of claim 1 , wherein the prodrug of castanospermine has the following structure:

wherein R 3 is (C 1 -C 14 ) acyl.

8 . The method of claim 1 , wherein the subject has a viral load reduction after receiving the alpha-glucosidase glycoprotein processing inhibitor of at least 50% greater than said subject not administered the alpha-glucosidase glycoprotein processing inhibitor or in a placebo-administered group.

9 . The method of claim 1 , wherein the SARS-COV-2 infection is from a SARS-COV-2 variant selected from the group consisting of B.1.1.7, B.1.351, and P.1.

10 . The method of claim 1 , wherein the alpha-glucosidase inhibitor is administered with a permeability enhancer.

11 . The method of claim 1 , wherein the human subject is further administered an antiviral drug, a monoclonal antibody treatment, a steroid, or COVID-19 convalescent plasma.

12 . The method of claim 11 , wherein the monoclonal antibody treatment is casirivimab, imdevimab, or bamlanivimab.

13 . The method of claim 11 , wherein the antiviral drug is remdesivir, chloroquine, hydroxychloroquine, or favipiravir.

14 . The method of claim 1 , wherein the human subject is further administered a second agent is selected from the group consisting of amikacin, amphotericin, atovaquone, Bactrim, clindamycin, corticosteroids, echinocandin, fluconazole, flucytosine, itraconazole, posaconazole, quinine, sulfa drugs, trimethoprimsulfamethoxazole, voriconazole, baricitinib, interleukin-6 inhibitors, tyrosine kinase inhibitors, Tocilizumab, ivermectin, and any combination thereof.