No abstract

COVID‐19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which infects host cells by binding its viral spike protein receptor‐binding domain (RBD) to the angiotensin converting enzyme 2 (ACE2) on host cells. Blocking the SARS‐CoV‐2‐RBD/ACE2 interaction is, therefore, a potential strategy to inhibit viral infections. Using a novel biopanning strategy, a small anti‐ACE2 peptide is discovered, which shows high affinity and specificity to human ACE2. It blocks not only the SARS‐CoV‐2‐RBD/ACE2 interaction but also the SARS‐CoV‐1‐RBD/ACE2 interaction. Moreover, it inhibits SARS‐CoV‐2 infection in Vero‐E6 cells. The peptide shows negligible cytotoxicity in Vero‐E6 cells and Huh7 cells. In vivo short‐term lung toxicity study also demonstrates a good safety of the peptide after intratracheal administration. The anti‐ACE2 peptide can be potentially used as a prophylactic or therapeutic agent for SARS‐CoV‐2 or other ACE2‐mediated viruses. The strategy used in this study also provides a fast‐track platform to discover other antiviral peptides, which will prepare the world for future pandemics.

Spousal separation, lack of companionship, and increased household responsibilities may trigger mental health problems in left-behind female spouses of migrant workers. This study aimed to examine mental ill-health risk in the left-behind female spouses of international migrant workers in Nepal. A cross-sectional survey was carried out in the Nawalparasi district. Study areas were purposively chosen; however, participants were randomly selected. Nepali versions of the 12-item General Health Questionnaire (GHQ), Beck Depression Inventory (BDI), and Connor–Davidson Resilience Scale (CD-RISC) were used. Mental ill-health risk was prevalent in 3.1% of the participants as determined by GHQ. BDI identified mild or moderate depression in 6.5% of the participants with no one having severe depression. In bivariate analysis, a high frequency of communication with the husband was associated with lower mental ill-health risk and depression, as well as increasing resilience. Reduced return intervals of husbands and a high frequency of remittance were also associated with a low GHQ score. In a multiple regression model, adjusting for potential confounding variables, participants who communicated with their husbands at least once a day had a greater mean CD-RISC score (i.e., high resilience against mental ill-health risk) compared to those who did so at least once a week; a mean difference of 3.6 (95% CI 0.4 to 6.9), P = 0.03. To conclude, a low mental ill-health risk was found in the female spouses of migrants.

Blockade of the interaction between programmed cell death ligand-1 (PD-L1) and its receptor PD-1 has shown great success in cancer immunotherapy. Peptides possess unique characteristics that give them significant advantages as immune checkpoint inhibitors. However, unfavorable physicochemical properties and proteolytic stability profiles limit the translation of bioactive peptides as therapeutic agents. Studies have revealed that cyclization improves the biological activity and stability of linear peptides. In this study, we report the use of macrocyclization scanning for the discovery of cyclic anti-PD-L1 peptides with improved bioactivity. The cyclic peptides demonstrated up to a 34-fold improvement in the PD-1/PD-L1 blocking activity and significant in vivo anti-tumor activity. Our results demonstrate that macrocyclization scanning is an effective way to improve the serum stability and bioactivity of the anti-PD-L1 linear peptide. This strategy can be employed in the optimization of other bioactive peptides, particularly those for protein–protein interaction modulation.

No abstract