RESUMO
The emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. As the development of a vaccine could require at least 12-18 months, and the typical timeline from hit finding to drug registration of an antiviral is >10 years, repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19. To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.
RESUMO
Systemic infection by MRSA (Methicillin-resistant Staphylococcus aureus) is a risk in immunodeficient patients such as those with severe burn injuries. Hozai, formulations with tonic effects, may enhance the immune system and we treated two severe burn patients with MRSA infections using Juzentaihoto, which is a remedy for kikyo (deficiency of vital energy) and kekkyo (ketsu deficiency). Both patients suffered flame burns [85% body surface area (BSA) and 40% BSA] and inhalation injuries committing self-immolation. They contracted MRSA in due course and antibiotics such as Arbekacin or Teicoplanin did not control MRSA. Therefore, Juzentaihoto was administered through a nasogastric tube and both of them were finally cured without complications. Juzentaihoto may be useful against fatigue, anemia, malaise, ulcer, and purulent wounds due to severe burns.
