The Journal of pharmacology and experimental therapeutics
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Coronavirus disease 2019 (COVID-19) is a novel disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus that was first detected in December of 2019 in Wuhan, China, and has rapidly spread worldwide. The search for a suitable vaccine as well as effective therapeutics for the treatment of COVID-19 is underway. Drug repurposing screens provide a useful and effective solution for identifying potential therapeutics against SARS-CoV-2. ⋯ A multitarget treatment approach with synergistic drug combinations containing different mechanisms of action may be a practical therapeutic strategy for the treatment of severe COVID-19. SIGNIFICANCE STATEMENT: Understanding the biology and pathology of RNA viruses is critical to accomplish the challenging task of developing vaccines and therapeutics against SARS-CoV-2. This review highlights the anti-SARS-CoV-2 drug targets and therapeutic development strategies for COVID-19 treatment.
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J. Pharmacol. Exp. Ther. · Oct 2020
Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice.
Cause-specific treatment and timely diagnosis are still not available for acute kidney injury (AKI) apart from supportive therapy and serum creatinine measurement. A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI with different causes, but the underlying mechanism is not fully defined. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with siRNA targeting caspase-3, an executing enzyme of apoptosis and inflammation (CASP3siRNA), on ischemia/reperfusion (IR)-induced AKI. ⋯ CHBP and CASP3siRNA synergistically protected kidney structure after 48-hour ischemia/reperfusion-induced AKI with reduced injury mediators CASP3 and high mobility group box 1. CHBP upregulated cell division-, function-, and metabolism-related genes, whereas CASP3siRNA further regulated immune response- and tissue homeostasis-associated genes. Combined CHBP and CASP3siRNA might be a potent and specific treatment for AKI, and certain dysregulated genes secretory leukocyte peptidase inhibitor and SERPINA3M could facilitate timely diagnosis.