ABSTRACT
Prevention of infection and propagation of SARS-CoV-2 is of high priority in the COVID-19 pandemic. Here, we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 Spike protein, thereby inhibiting viral entry, infectivity, and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and thus spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E-protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model, and thus provide a novel avenue for therapy.
ABSTRACT
OBJECTIVES: We attempted to explore of the nature of very early or mild Alzheimer disease due to its crucial importance in understanding natural history, assessment of therapeutic interventions and accurate estimation of prevalence and incidence of Alzheimer disease. METHODS: We compared the scores of cognitive functions measured with Cognitive Impairment Diagnosing Instrument(CIDI) in questionable dementia of Alzheimer type(QDAT), mild dementia of Alzheimer type(bHDAT), and control. The three groups were controlled for age, sex, and education. RESULTS: Total score of the CIDI was not significantly different between QDAT and MIDAT. The subjects with QDAT and MIDAT scored lower in short-term memory, concentration/calculation, and abstract thinking than controls, while the QDAT and MIDAT subjects scored similarly in those subjects of the CIDI. CONCLUSION: These findings suggest that QDAT may be very early or mild Alzheimer dementia.
