Up-regulation of caspase has been found in COVID-19 patients, and also occurs in patients suffering from diabetes, hypertension, metabolic syndrome, and other conditions. Such up-regulation can be responsible for poor clinical outcomes in patients having such diseases or disorders, as such up-regulation leads to a process called pyroptosis: death and malfunction of immune system cells, particularly of certain types of lymphocytes. An inhibitor of caspase such as a caspase 1 inhibitor, or “pan-caspase” inhibitor (i.e., an inhibitor of multiple caspase types including caspase-1), can be used to treat COVID-19 patients or individuals at risk of infection, by limiting the malfunction of the immune system. A caspase-1 or pan-caspase inhibitor is advantageously administered before or very early in the course of infection by a positive-sense, single-stranded RNA virus such as SARS-CoV, MERS-CoV, or SARS-Cov-2.

Up-regulation of caspase has been found in COVID-19 patients, and also occurs in patients suffering from diabetes, hypertension, metabolic syndrome, and other conditions. Such up-regulation can be responsible for poor clinical outcomes in patients having such diseases or disorders, as such up-regulation leads to a process called pyroptosis: death and malfunction of immune system cells, particularly of certain types of lymphocytes. An inhibitor of caspase such as a caspase 1 inhibitor, or “pan-caspase” inhibitor (i.e., an inhibitor of multiple caspase types including caspase-1), can be used to treat COVID-19 patients or individuals at risk of infection, by limiting the malfunction of the immune system. A caspase-1 or pan-caspase inhibitor is advantageously administered before or very early in the course of infection by a positive-sense, single-stranded RNA virus such as SARS-CoV, MERS-CoV, or SARS-Cov-2.

By a Selective Elimination of Host Cells Capable of Producing HIV (SECH) approach, which includes a combination of latency reversal, blocking of new infections, inhibition of autophagy and induction of apoptosis, host cells harboring productive HIV infections can be cleared from a subject. Disclosed herein are methods for treating or inhibiting HIV in a subject, comprising a) reactivating latent HIV integrated into the genome of a cell infected with HIV in the subject, b) optionally administering to the subject an effective amount of a therapeutic agent to inhibit HIV infection, and c) administering to the subject an effective amount of a therapeutic agent to eliminate or reduce the number of cells containing replication-competent HIV. Kits for treating or inhibiting HIV in a subject are also disclosed.

By a Selective Elimination of Host Cells Capable of Producing HIV (SECH) approach, which includes a combination of latency reversal, blocking of new infections, inhibition of autophagy and induction of apoptosis, host cells harboring productive HIV infections can be cleared from a subject. Disclosed herein are methods for treating or inhibiting HIV in a subject, comprising a) reactivating latent HIV integrated into the genome of a cell infected with HIV in the subject, b) optionally administering to the subject an effective amount of a therapeutic agent to inhibit HIV infection, and c) administering to the subject an effective amount of a therapeutic agent to eliminate or reduce the number of cells containing replication-competent HIV. Kits for treating or inhibiting HIV in a subject are also disclosed.

Pharmaceutical compositions comprising: one or more bromodomain and extra terminal domain (BET) proteolysis targeting chimera (PROTAC) (BET-PROTAC) therapeutic agents or one or more cyclin-dependent kinase 9 (CDK9) PROTAC (CDK9-PROTAC) therapeutic agents; and one or more kinase inhibitors, one or more KRAS inhibitors, or one or more autophagy inhibitors; and methods of treating cancer in a human patient by administering such pharmaceutical compositions are described herein.

##STR00001##

Pharmaceutical compositions comprising: one or more bromodomain and extra terminal domain (BET) proteolysis targeting chimera (PROTAC) (BET-PROTAC) therapeutic agents or one or more cyclin-dependent kinase 9 (CDK9) PROTAC (CDK9-PROTAC) therapeutic agents; and one or more kinase inhibitors, one or more KRAS inhibitors, or one or more autophagy inhibitors; and methods of treating cancer in a human patient by administering such pharmaceutical compositions are described herein.

##STR00001##

Pharmaceutical compositions comprising: one or more bromodomain and extra terminal domain (BET) proteolysis targeting chimera (PROTAC) (BET-PROTAC) therapeutic agents or one or more cyclin-dependent kinase 9 (CDK9) PROTAC (CDK9-PROTAC) therapeutic agents; and one or more kinase inhibitors, one or more KRAS inhibitors, or one or more autophagy inhibitors; and methods of treating cancer in a human patient by administering such pharmaceutical compositions are described herein.

##STR00001##

The present invention relates to compounds of formula (I) or the tautomers or pharmacologically acceptable acid addition salts thereof, characterized by a topological polar surface area value (TPSA) of at least 145, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, and Z.sup.− have one of the meanings as defined in the specification, to the use of compounds of formula (I) as medicaments, to pharmaceutical compositions comprising at least one compound of formula (I), as well as to medicament combinations containing one or more compounds of formula (I). The compounds are ENaC inhibitors useful for the treatment of respiratory diseases and allergic diseases of the airways.

##STR00001##

The present invention relates to compounds of formula (I) or the tautomers or pharmacologically acceptable acid addition salts thereof, characterized by a topological polar surface area value (TPSA) of at least 145, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, and Z.sup.− have one of the meanings as defined in the specification, to the use of compounds of formula (I) as medicaments, to pharmaceutical compositions comprising at least one compound of formula (I), as well as to medicament combinations containing one or more compounds of formula (I). The compounds are ENaC inhibitors useful for the treatment of respiratory diseases and allergic diseases of the airways.

##STR00001##

The present disclosure provides compositions and methods for reactivating latent immunodeficiency virus and/or reducing transcription of HIV integrated into the genome of an HIV-infected cell. The present disclosure provides compositions and methods for treating an immunodeficiency virus infection.