The present invention relates to MEK inhibitors that are capable of displaying one or more beneficial therapeutic effects. The MEK inhibitors can be used in the prevention and/or treatment of hantavirus infection.

The present disclosure relates to compounds that act as protein kinase inhibitors, especially CK1δ and/or CK1ε inhibitors, which can be used to treat a serine threonine kinase-dependent disease and condition, such as neurodegenerative diseases like Alzheimer's Disease, and the synthesis of the same. Further, the present disclosure teaches the utilization of such compounds in a treatment for neurodegenerative diseases, including Alzheimer's disease.

Embodiments of the technology described herein are based upon the discoveries that neutrophil extracellular traps (NETs) provide a stimulus for thrombus formation and that NETs are present in stored blood products. Accordingly, some embodiments relate to methods of treating and preventing toxicity of NETs and thrombosis caused by NETs. Additional embodiments are directed towards methods of treating stored blood products to prevent transfusion-related injuries.

Embodiments of the technology described herein are based upon the discoveries that neutrophil extracellular traps (NETs) provide a stimulus for thrombus formation and that NETs are present in stored blood products. Accordingly, some embodiments relate to methods of treating and preventing toxicity of NETs and thrombosis caused by NETs. Additional embodiments are directed towards methods of treating stored blood products to prevent transfusion-related injuries.

The present invention relates to MEK inhibitors that are capable of displaying one or more beneficial therapeutic effects. The MEK inhibitors can be used in the prevention and/or treatment of viral infection. MEK inhibitors in combination with a cap-dependent endonuclease inhibitor are capable of displaying one or more beneficial therapeutic effects in the treatment of viral diseases.

The present invention relates to MEK inhibitors that are capable of displaying one or more beneficial therapeutic effects. The MEK inhibitors can be used in the prevention and/or treatment of viral infection. MEK inhibitors in combination with a cap-dependent endonuclease inhibitor are capable of displaying one or more beneficial therapeutic effects in the treatment of viral diseases.

The present invention relates to the early treatment, including pre-diagnosis treatment, of sepsis and acute inflammatory syndromes such as systemic inflammatory response syndrome (SIRS) by PLA2 and metalloprotease inhibitors to improve the performance of antibiotics and outcomes prior to and after confirmation of the diagnosis of sepsis and/or SIRS in a patient or subject. Additional embodiments include methods of treating sepsis, anthrax and severe acute respiratory syndrome coronavirus (SARS and SARS-CoV2) and related inflammatory syndromes and compositions, including pharmaceutical compositions and blood sample compositions. In further embodiments, the present invention is directed to embodiments which evidence that LY315920, LY333013 and related sPLA2 inhibitors are particularly effective COVID-19/cytokine release syndrome therapeutics-prophylactics. In embodiments, the PLA2 inhibitor is varespladib (LY315920), methyl varespladib (LY333013), AZD2716-(R)-3-(5′-benzyl-2′-carbamoyl-[1,1′-biphenyl-3-yl)-2-methylpropanoic acid—as a racemic mixture or separately, as the “R” enantiomer), AZD Compound 4 (3-(5′-Benzyl-2′-carbamoylbiphenyl-3-yl)propanoic acid) and LY433771 ((9-[(phenyl)methyl]-5-carbamoylcarbazol-4-yl) oxyacetic acid), a pharmaceutically acceptable salt thereof or a mixture thereof. In embodiments, the metalloprotease inhibitor is Prinomastat, Batimastat, marimastat or vorinostat dosed alone or in combination with preferred sPLA2 inhibitors for the treatment of infection, inflammatory and wound conditions arising from various causes. Methods and compositions for achieving accelerated. treatment of wounds and burns, anthrax metalloprotease toxin (lethal factor) driven complications, ARDS, neo-natal and pediatric acute respiratory distress syndrome (neo-natal/pediatric ARDS), including, meconium aspiration syndrome are also disclosed.

The present invention relates to the early treatment, including pre-diagnosis treatment, of sepsis and acute inflammatory syndromes such as systemic inflammatory response syndrome (SIRS) by PLA2 and metalloprotease inhibitors to improve the performance of antibiotics and outcomes prior to and after confirmation of the diagnosis of sepsis and/or SIRS in a patient or subject. Additional embodiments include methods of treating sepsis, anthrax and severe acute respiratory syndrome coronavirus (SARS and SARS-CoV2) and related inflammatory syndromes and compositions, including pharmaceutical compositions and blood sample compositions. In further embodiments, the present invention is directed to embodiments which evidence that LY315920, LY333013 and related sPLA2 inhibitors are particularly effective COVID-19/cytokine release syndrome therapeutics-prophylactics. In embodiments, the PLA2 inhibitor is varespladib (LY315920), methyl varespladib (LY333013), AZD2716-(R)-3-(5′-benzyl-2′-carbamoyl-[1,1′-biphenyl-3-yl)-2-methylpropanoic acid—as a racemic mixture or separately, as the “R” enantiomer), AZD Compound 4 (3-(5′-Benzyl-2′-carbamoylbiphenyl-3-yl)propanoic acid) and LY433771 ((9-[(phenyl)methyl]-5-carbamoylcarbazol-4-yl) oxyacetic acid), a pharmaceutically acceptable salt thereof or a mixture thereof. In embodiments, the metalloprotease inhibitor is Prinomastat, Batimastat, marimastat or vorinostat dosed alone or in combination with preferred sPLA2 inhibitors for the treatment of infection, inflammatory and wound conditions arising from various causes. Methods and compositions for achieving accelerated. treatment of wounds and burns, anthrax metalloprotease toxin (lethal factor) driven complications, ARDS, neo-natal and pediatric acute respiratory distress syndrome (neo-natal/pediatric ARDS), including, meconium aspiration syndrome are also disclosed.

In alternative embodiments, provided are methods for treating, ameliorating, decreasing the chances of having any adverse effects from, decreasing the severity of adverse effects from, or preventing an infection by administration of an antibiotic and/or an anti-viral drugs and a vaccine directed to a causative agent of the infection and/or an attenuated and/or a live, viable or infectious causative agent of the infection. In alternative embodiments, the infection is bacterial or viral. In alternative embodiments, the viral infection is a coronavirus infection such a Covid-19 infection. In alternative embodiments, methods as provide herein prevent or decrease the prevalence or severity of “vaccine breakthrough infections” after vaccination, where external mutants of COVID-19 infect patients in spite of the fact that they have undergone immunization, for example, to prevent a mutant or variant COVID-19 infection. In alternative embodiments, an antiviral combination administered in coordination with a vaccine comprises PF-07321332 or PAXLOVID™ and/or ritonavir, or ivermectin, doxycycline and a zinc or a zinc salt. In alternative embodiments, methods as provided herein are used to prevent in vivo mutations of such mutant infectious agent to enhance the efficacy of an administered vaccination; in other words, methods as provided herein are used to prevent in vivo replication of an acquired viral mutant or variant infectious agent, and thus also prevents ongoing mutations of the viral infectious agent because using the combination antiviral co-therapy where there is no replication of infectious agent and so there is no possible further mutation of the infectious agent.

In alternative embodiments, provided are methods for treating, ameliorating, decreasing the chances of having any adverse effects from, decreasing the severity of adverse effects from, or preventing an infection by administration of an antibiotic and/or an anti-viral drugs and a vaccine directed to a causative agent of the infection and/or an attenuated and/or a live, viable or infectious causative agent of the infection. In alternative embodiments, the infection is bacterial or viral. In alternative embodiments, the viral infection is a coronavirus infection such a Covid-19 infection. In alternative embodiments, methods as provide herein prevent or decrease the prevalence or severity of “vaccine breakthrough infections” after vaccination, where external mutants of COVID-19 infect patients in spite of the fact that they have undergone immunization, for example, to prevent a mutant or variant COVID-19 infection. In alternative embodiments, an antiviral combination administered in coordination with a vaccine comprises PF-07321332 or PAXLOVID™ and/or ritonavir, or ivermectin, doxycycline and a zinc or a zinc salt. In alternative embodiments, methods as provided herein are used to prevent in vivo mutations of such mutant infectious agent to enhance the efficacy of an administered vaccination; in other words, methods as provided herein are used to prevent in vivo replication of an acquired viral mutant or variant infectious agent, and thus also prevents ongoing mutations of the viral infectious agent because using the combination antiviral co-therapy where there is no replication of infectious agent and so there is no possible further mutation of the infectious agent.