ABSTRACT
Currently an emerging human pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused coronavirus disease 2019 (COVID-19) that has posed a serious threat to public health worldwide. As it is a novel severe pneumonia-type viral disease, no effective therapeutic agents are available to treat this infection to date, emphasizing an urgent need for development of effective anti-SARS-CoV-2 agents. Based on screening in computational biology and biological in vitro assays, a good number of natural compounds and their synthetic analogues have been confirmed to possess target-specific inhibitory effects against the activity of host and viral proteases, namely, cathepsin-L, TMPRSS2, Sec61, Mpro (3CL-protease), RNA-dependent RNA protease (RdRp), helicase cap-binding proteases eEF1A, eIF4A, eIF4E, which play dominant roles in progression of infection and replication of SARS-CoV-2 virus in host cells. This review paper describes the potent antiviral activity and target-specific anti-proteases activity of some natural compounds and their synthetic analogues against SARS-CoV-2 infection. It will inspire the researchers to unleash their own creativity and to design potent and safe drugs to fight the current COVID-19 pandemic.
ABSTRACT
BACKGROUND: Antibiotic exposure in the pediatric intensive care unit (PICU) is very high, although 50% of all antibiotics may be unnecessary. We aimed to determine the utility of simple bedside screening tools and predicting factors to avoid antibiotic overuse in the ICU among children with diarrhea and critical illness. METHODS: We conducted a retrospective, single-center, case-control study that included children aged 2-59 months who were admitted to PICU with diarrhea and critical illness between 2017 and 2020. RESULTS: We compared young children who did not receive antibiotics (cases, n = 164) during ICU stay to those treated with antibiotics (controls, n = 346). For predicting the 'no antibiotic approach', the sensitivity of a negative quick Sequential Organ Failure Assessment (qSOFA) was similar to quick Pediatric Logistic Organ Dysfunction-2 (qPELOD-2) and higher than Systemic Inflammatory Response Syndrome (SIRS). A negative qSOFA or qPELOD-2 score calculated during PICU admission is superior to SIRS to avoid antibiotic overuse in under-five children. The logistic regression analysis revealed that cases were more often older and independently associated with hypernatremia. Cases less often had severe underweight, altered mentation, age-specific fast breathing, lower chest wall in-drawing, adventitious sound on lung auscultation, abdominal distension, developmental delay, hyponatremia, hypocalcemia, and microscopic evidence of invasive diarrhea (for all, p < 0.05). CONCLUSION: Antibiotic overuse could be evaded in PICU using simple bedside screening tools and clinical characteristics, particularly in poor resource settings among children with diarrhea.
ABSTRACT
Rapid synthesis of the pentacyclic core structure of macroline-type indole alkaloids, and its application in the total synthesis of macroline and alstomicine is described. The core structure was accomplished in a highly stereocontrolled manner via two key steps, Ireland-Claisen rearrangement and Pictet-Spengler cyclization, commencing from a readily available starting material l-tryptophan, which obviated the need of a particular chiral source as an external catalyst, reagent, or internal auxiliary.