Pattern and perceived changes in quality of life of Vietnamese medical and nursing students during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic and governments' response lead to dramatical change in quality of life worldwide. However, the extent of this change in Vietnamese medical and nursing students has not been documented. OBJECTIVES: The study aims to describe the quality of life and changes in quality of life of medical and nursing students during the COVID-19 pandemic and examine the association of quality of life and changes in quality of life with fear of COVID-19 and other socio-economic and demographic factors. METHODS: The study was a cross-sectional study on all students of Hanoi Medical University from 3 majors: General Medicine, Preventive Medicine, Nursing (3672 invited students); from 7th to 29th of April 2020; using an online questionnaire that included demographic and academic information, the Vietnamese version of the SF-36 Quality of Life questionnaire and the Fear of COVID-19 Scale (FCV-19S). Linear and modified Poisson regression was used to examine the association between quality of life, changes in quality of life and other factors. RESULTS: The number of participants was 1583 (response rate 43%). Among 8 dimensions of the SF-36 (ranged 0-100), Vitality had the lowest score with a median score of 46. The median physical composite score (PCS) of the sample was 40.6 (IQR:20.8-53.2), 33.5% of the sample had an above-population average PCS score. The median mental composite score (MCS) of the sample was 20.3 (IQR:3.8-31.7), and 98.2% had an MCS score below average. 9.9% (95%CI:8.5%-11.4%) of the population reported a significant negative change in the quality of life. Fear of COVID-19 was not associated with significant changes in quality of life, nor MCS while having some association with PCS (Coef:-5.39;95%CI:-3to-7.8). Perceived reduction in quality of life was also associated with: being on clinical rotation COVID-19 (PR:1.5;95%CI:1.05-2.2), difficulties affording health services (PR:1.4;95%CI:1.02-1.95), obesity (PR:2.38;95%CI:1.08-5.25) and chronic disease (PR:1.92;95%CI:1.23-3), typical symptoms (PR:1.85; 95%CI:1.23-2.78) and atypical symptoms of COVID-19 (PR:2.32;95%CI:1.41-3.81). CONCLUSION: The majority of medical and nursing students had below average quality of life, with lower vitality and mental composite health score in the settings of COVID-19. Perceived decrease in quality of life was associated with clinical rotation, difficulties affording healthcare services and was not associated with Fear of COVID-19.

Rational design of thioamide peptides as selective inhibitors of cysteine protease cathepsin L† † Electronic supplementary information (ESI) available: Descriptions of materials and methods, including peptide synthesis, characterization, and purification, protease assays, validation of protease assays with HPLC and MS, details on cell lysate assay and inhibition assays. See DOI: 10.1039/d1sc00785h

Aberrant levels of cathepsin L (Cts L), a ubiquitously expressed endosomal cysteine protease, have been implicated in many diseases such as cancer and diabetes. Significantly, Cts L has been identified as a potential target for the treatment of COVID-19 due to its recently unveiled critical role in SARS-CoV-2 entry into the host cells. However, there are currently no clinically approved specific inhibitors of Cts L, as it is often challenging to obtain specificity against the many highly homologous cathepsin family cysteine proteases. Peptide-based agents are often promising protease inhibitors as they offer high selectivity and potency, but unfortunately are subject to degradation in vivo. Thioamide substitution, a single-atom O-to-S modification in the peptide backbone, has been shown to improve the proteolytic stability of peptides addressing this issue. Utilizing this approach, we demonstrate herein that good peptidyl substrates can be converted into sub-micromolar inhibitors of Cts L by a single thioamide substitution in the peptide backbone. We have designed and scanned several thioamide stabilized peptide scaffolds, in which one peptide, RS1A, was stabilized against proteolysis by all five cathepsins (Cts L, Cts V, Cts K, Cts S, and Cts B) while inhibiting Cts L with >25-fold specificity against the other cathepsins. We further showed that this stabilized RS1A peptide could inhibit Cts L in human liver carcinoma lysates (IC50 = 19 μM). Our study demonstrates that one can rationally design a stabilized, specific peptidyl protease inhibitor by strategic placement of a thioamide and reaffirms the place of this single-atom modification in the toolbox of peptide-based rational drug design. Information on the effects of sidechain and backbone modification on the activity of cathepsin (Cts) L, V, K, S, and B was used to design a thioamide peptide that is inert to all Cts and selectively inhibits Cts L.

Rational design of thioamide peptides as selective inhibitors of cysteine protease cathepsin L.

Aberrant levels of cathepsin L (Cts L), a ubiquitously expressed endosomal cysteine protease, have been implicated in many diseases such as cancer and diabetes. Significantly, Cts L has been identified as a potential target for the treatment of COVID-19 due to its recently unveiled critical role in SARS-CoV-2 entry into the host cells. However, there are currently no clinically approved specific inhibitors of Cts L, as it is often challenging to obtain specificity against the many highly homologous cathepsin family cysteine proteases. Peptide-based agents are often promising protease inhibitors as they offer high selectivity and potency, but unfortunately are subject to degradation in vivo. Thioamide substitution, a single-atom O-to-S modification in the peptide backbone, has been shown to improve the proteolytic stability of peptides addressing this issue. Utilizing this approach, we demonstrate herein that good peptidyl substrates can be converted into sub-micromolar inhibitors of Cts L by a single thioamide substitution in the peptide backbone. We have designed and scanned several thioamide stabilized peptide scaffolds, in which one peptide, RS 1A, was stabilized against proteolysis by all five cathepsins (Cts L, Cts V, Cts K, Cts S, and Cts B) while inhibiting Cts L with >25-fold specificity against the other cathepsins. We further showed that this stabilized RS 1A peptide could inhibit Cts L in human liver carcinoma lysates (IC50 = 19 µM). Our study demonstrates that one can rationally design a stabilized, specific peptidyl protease inhibitor by strategic placement of a thioamide and reaffirms the place of this single-atom modification in the toolbox of peptide-based rational drug design.

Fixed single-cell RNA sequencing for understanding virus infection and host response.

Single-cell transcriptomic studies that require intracellular protein staining, rare cell sorting, or inactivation of infectious pathogens are severely limited because current high-throughput RNA sequencing methods are incompatible with paraformaldehyde treatment, a common tissue and cell fixation and preservation technique. Here we present FD-seq, a high-throughput method for droplet-based RNA sequencing of paraformaldehyde-fixed, stained and sorted single-cells. We show that FD-seq preserves the mRNA integrity and relative abundances during fixation and subsequent cell retrieval. Furthermore, FD-seq detects a higher number of genes and transcripts than methanol fixation. We applied FD-seq to investigate two important questions in Virology. First, by analyzing a rare population of cells supporting lytic reactivation of the human tumor virus KSHV, we identified TMEM119 as a host factor that mediates viral reactivation. Second, we found that upon infection with the betacoronavirus OC43, which causes the common cold and is a close relative of SARS-CoV-2, pro-inflammatory pathways are primarily upregulated in lowly-infected cells that are exposed to the virus but fail to express high levels of viral genes. FD-seq thus enables integrating phenotypic with transcriptomic information in rare cell populations, and preserving and inactivating pathogenic samples that cannot be handled under regular biosafety measures.