Methods of treating SARS-CoV-2 infections
The disclosure is directed to methods of using dantrolene or a dantrolene prodrug, or a pharmaceutically acceptable salt thereof, to treat COVID-19 and SARS-CoV-2 infections.
1 . A method of treating COVID-19 in a subject comprising administering to the subject dantrolene or a pharmaceutically acceptable salt thereof, or by administering a compound of Formula I:
wherein R is —P(O)(OH) 2 or —P(O)(OR 1 )(OR 2 ); R 1 is H, —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; and R 2 is —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , comprising administering dantrolene to the subject.
3 . The method of claim 1 , comprising administering a pharmaceutically acceptable salt of dantrolene to the subject.
4 . The method of claim 1 , comprising administering dantrolene sodium to the subject.
5 . The method of claim 1 , wherein the administration results in at least a 1-point decrease in the subject's WHO Ordinal Scale score, as compared to baseline.
6 . The method of claim 1 , wherein the administration results in an improvement in the subject's Sequential Organ Failure Assessment daily score, as compared to baseline.
7 . The method of claim 1 , wherein the administration results in a reduction of time to normalization of fever in the subject, as compared to the amount of time to normalization of fever in a control subject.
8 . The method of claim 1 , wherein the administration results in a reduction of time to normalization of oxygen saturation in the subject, as compared to the amount of time to normalization of oxygen saturation in a control subject.
9 . A method for inhibiting replication of SARS-CoV-2 in a subject comprising administering to the subject dantrolene, or a pharmaceutically acceptable salt thereof, or by administering a compound of Formula I:
wherein R is —P(O)(OH) 2 or —P(O)(OR 1 )(OR 2 ); R 1 is H, —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; and R 2 is —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; or a pharmaceutically acceptable salt thereof.
10 . The method of claim 9 , comprising administering dantrolene to the subject.
11 . The method of claim 9 , comprising administering a pharmaceutically acceptable salt of dantrolene to the subject.
12 . The method of claim 9 , comprising administering dantrolene sodium to the subject.
13 . A method for inhibiting replication of SARS-CoV-2 in a host cell, for inhibiting entry of SARS-CoV-2 into a host cell, for inhibiting SARS-CoV-2 virion maturation in a host cell, or for inhibiting release of SARS-CoV-2 from a host cell comprising administering to the host cell dantrolene, or a pharmaceutically acceptable salt thereof, or by administering a compound of Formula I:
wherein R is —P(O)(OH) 2 or —P(O)(OR 1 )(OR 2 ); R 1 is H, —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; and R 2 is —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; or a pharmaceutically acceptable salt thereof.
14 . The method of claim 13 , comprising administering dantrolene to the host cell.
15 . The method of claim 13 , comprising administering a pharmaceutically acceptable salt of dantrolene to the host cell.
16 . The method of claim 13 , comprising administering dantrolene sodium to the host cell.
17 . A method for reducing the infectivity of SARS-CoV-2 by administering to a host cell dantrolene, or a pharmaceutically acceptable salt thereof, or by administering a compound of Formula I:
wherein R is —P(O)(OH) 2 or —P(O)(OR 1 )(OR 2 ); R 1 is H, —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; and R 2 is —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; or a pharmaceutically acceptable salt thereof.
18 . The method of claim 17 , comprising administering dantrolene to the host cell.
19 . The method of claim 17 , comprising administering a pharmaceutically acceptable salt of dantrolene to the host cell.
20 . The method of claim 17 , comprising administering dantrolene sodium to the host cell.
21 . The method of claim 1 , wherein the compound of Formula I is:
wherein R is —P(O)(OH) 2 .
22 . The method of claim 9 , wherein the compound of formula I is:
wherein R is —P(O)(OH) 2 .
23 . The method of claim 13 , wherein the compound of Formula I is:
wherein R is —P(O)(OH) 2 .
24 . The method of claim 17 , wherein the compound of Formula I is:
wherein R is —P(O)(OH) 2 .