Developing inhibitory peptides against SARS-CoV-2 envelope protein.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected approximately 800 million people since the start of the Coronavirus Disease 2019 (COVID-19) pandemic. Because of the high rate of mutagenesis in SARS-CoV-2, it is difficult to develop a sustainable approach for prevention and treatment. The Envelope (E) protein is highly conserved among human coronaviruses. Previous studies reported that SARS-CoV-1 E deficiency reduced viral propagation, suggesting that E inhibition might be an effective therapeutic strategy for SARS-CoV-2. Here, we report inhibitory peptides against SARS-CoV-2 E protein named iPep-SARS2-E. Leveraging E-induced alterations in proton homeostasis and NFAT/AP-1 pathway in mammalian cells, we developed screening platforms to design and optimize the peptides that bind and inhibit E protein. Using Vero-E6 cells, human-induced pluripotent stem cell-derived branching lung organoid and mouse models with SARS-CoV-2, we found that iPep-SARS2-E significantly inhibits virus egress and reduces viral cytotoxicity and propagation in vitro and in vivo. Furthermore, the peptide can be customizable for E protein of other human coronaviruses such as Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The results indicate that E protein can be a potential therapeutic target for human coronaviruses.

Association between the dexamethasone suppression test and serotonin transporter availability in healthy volunteer: a SPECT with [(123)I] ADAM study.

Most common psychiatric diseases have been found to be associated with disturbance of both the hypothalamic-pituitary-adrenal (HPA) axis and the brain serotonergic system. The aim of this study was to explore the neuroendocrine relationships between the dexamethasone suppression test (DST) and serotonin transporter (SERT) availability in healthy volunteers. Sixty-six participants (30 males and 36 females) were recruited from the community. The DST suppression rate (D%) is the reduction in cortisol level from Day 1 (D1) to Day 2 (D2) in proportion to the Day 1 cortisol level (D%=(D1-D2)/D1×100%). SPECT with [(123)I] ADAM was used to measure SERT availability. A significant correlation between D% and SERT availability was noted in all subjects (Spearman's ρ=0.26, p=0.03) and in the male subjects (Spearman's ρ=0.41, p=0.02). SERT availability may be sensitive to changes in DST, especially in males.

Sunshine-exposure variation of human striatal dopamine D(2)/D(3) receptor availability in healthy volunteers.

BACKGROUND: In addition to the serotonergic system, the central dopaminergic system has been reported to be correlated with seasonality. The aim of this study was to explore the difference in striatal dopamine D(2)/D(3) receptor availability between healthy volunteers who had a high-sunshine exposure and those who had a low exposure. METHODS: Sixty-eight participants were enrolled, and those in the upper and lower quartiles in terms of sunshine exposure were categorized into high- (n = 17) and low-sunshine-exposure (n = 18) subgroups. Single photon emission computed tomography with [(123)I] iodo-benzamide was used to measure striatal dopamine D(2)/D(3) receptor availability. RESULTS: Striatal dopamine D(2)/D(3) receptor availability was significantly greater in the subjects with high-sunshine exposure than in those with low-sunshine exposure (F = 7.97, p = 0.01) after controlling for age, sex, and smoking status. LIMITATIONS: Different subjects were examined at different time points in our study. In addition, the sex and tobacco use distributions differed between groups. CONCLUSION: The central dopaminergic system may play a role in the neurobiological characteristics of sunshine-exposure variation.

Electrocardiographic abnormalities as predictors for over-range lithium levels.

BACKGROUND: Lithium compounds have been widely used in the treatment of manic-depressive illness. Several electrocardiogram (ECG) abnormalities, including ventricular arrhythmias, atrioventricular conduction abnormalities, T wave changes and QT interval prolongation, have been reported to be associated with lithium. However, the correlation between serum lithium levels and ECG changes has never been characterized in a systematic way. METHODS: This retrospective study included 76 patients undergoing lithium treatment with available records of lithium levels. Eleven patients (4 men) had serum lithium levels >1.2 mEq/l and were diagnosed as lithium over range. Clinical characteristics and various ECG changes were analyzed in patients with and without lithium over range. RESULTS: Patients with lithium over range had a slower heart rate and longer PR, QT and corrected QT (QTc) intervals. QTc interval >440 ms was more commonly found in patients with lithium over range (55 vs. 8%, p < 0.001). Similarly, diffuse T wave inversion was more commonly associated with lithium over range (73 vs. 17%, p < 0.001). The daily dosage of lithium was similar between patients with and without over-range lithium levels. When these two ECG changes were combined, the sensitivity and specificity in predicting lithium over range were 64 and 97%, respectively. These findings were independent of the concomitant use of beta-blockers. CONCLUSIONS: QTc interval >440 ms and diffuse T wave inversion were significantly more common in patients with lithium over range, and were good predictors of lithium over range. More liberal checkup of the ECG in patients undergoing lithium treatment may be of help in the early detection of lithium over range.