Mpro-targeted anti-SARS-CoV-2 inhibitor-based drugs.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global health emergency. The main protease is an important drug target in coronaviruses. It plays an important role in the processing of viral RNA-translated polyproteins and is highly conserved in the amino acid sequence and three-dimensional structure, making it a good drug target for which several small molecule inhibitors are available. This paper describes the various anti-severe acute respiratory syndrome coronavirus 2 inhibitor drugs targeting Mpro discovered since the severe acute respiratory syndrome coronavirus 2 outbreak at the end of 2019, with all these compounds inhibiting severe acute respiratory syndrome coronavirus 2 Mpro activity in vitro. This provides a reference for the development of severe acute respiratory syndrome coronavirus 2 Mpro-targeted inhibitors and the design of therapeutic approaches to address newly emerged severe acute respiratory syndrome coronavirus 2 mutant strains with immune evasion capabilities.

Occupations Associated With Poor Cardiovascular Health in Women: The Women's Health Initiative Observational Study.

INTRODUCTION: Research on the effect of occupation on cardiovascular health (CVH) among older women is limited. METHODS: Each of the seven American Heart Association's CVH metrics was scored as ideal (1) or non-ideal (0) and summed. Multivariable logistic regression was used to estimate the odds of poor overall CVH (CVH score of 0 to 2) comparing women employed in each of the top 20 occupational categories to those not employed in that category, adjusting for age, marital status, and race/ethnicity. RESULTS: (1) Bookkeeping, accounting, and auditing clerks; (2) first-line supervisors of sales workers; (3) first-line supervisors of office and administrative support workers; and (4) nursing, psychiatric, and home health aides were more likely to have poor overall CVH compared to women who did not work in these occupations. CONCLUSIONS: Several commonly held occupations among women were associated with poor CVH.

Associations of Job Strain, Stressful Life Events, and Social Strain With Coronary Heart Disease in the Women's Health Initiative Observational Study.

Background The association between psychosocial stress and coronary heart disease (CHD) may be stronger in women than men and may differ across types of stressors. In this study, we assessed associations of psychosocial stressors, including job strain, stressful life events, and social strain with the incidence of CHD in women. Methods and Results We used longitudinal data from 80 825 WHI-OS (Women's Health Initiative Observational Study) participants with a mean age of 63.4 years (7.3 years) at baseline. Job strain was assessed through linkage of Standard Occupational Classification codes to the Occupational Information Network. Stressful life events and social strain were assessed via validated self-reported questionnaires. Cox proportional hazard models were used to evaluate associations of each stressor with CHD separately and jointly. A total of 3841 (4.8%) women developed CHD during an average of 14.7 years of follow-up. After adjustment for age, other stressors, job tenure, and socioeconomic factors, high stressful life events score was associated with a 12% increased CHD risk, and high social strain was associated with a 9% increased CHD risk. Job strain was not independently associated with CHD risk, but we observed a statistically significant interaction between job strain and social strain (P=0.04), such that among women with high social strain, passive job strain was associated with a 21% increased CHD risk. Conclusions High stressful life events and social strain were each associated with higher CHD risk. Job strain and social strain work synergistically to increase CHD risk.

Occupations Associated with Poor Cardiovascular Health in Women: The Women's Health Initiative Observational Study.

INTRODUCTION: Research on the effect of occupation on cardiovascular health (CVH) among older women is limited. METHODS: Each of the 7 American Heart Association's CVH metrics was scored as ideal (1) or non-ideal (0) and summed. Multivariable logistic regression was used to estimate the odds of poor overall CVH (CVH score of 0-2) comparing women employed in each of the top 20 occupational categories to those not employed in that category, adjusting for age, marital status, and race/ethnicity. RESULTS: 1) Bookkeeping, accounting, and auditing clerks; 2) first-line supervisors of sales workers; 3) first-line supervisors of office and administrative support workers; and 4) nursing, psychiatric, and home health aides were more likely to have poor overall CVH compared to women who did not work in these occupations. CONCLUSIONS: Several commonly held occupations among women were associated with poor CVH.

Occupational Physical Activity and Coronary Heart Disease in Women's Health Initiative Observational Study.

BACKGROUND: Women comprise nearly half of the labor force in our society, but the impact of the occupational psychical activity on women's heart health in later life was unclear. We conducted a case-cohort study to assess the association of occupational physical activity (OPA), alone and jointly with leisure-time physical activity (LTPA) and risk of coronary heart disease (CHD). METHODS: We included women enrolled in Women's Health Initiative Observational Study who provided an occupational history at baseline and were followed until 2013 for the first occurrence of myocardial infarction or death from CHD (mean age ± SD = 63.4 ± 7.2). A total of 5,243 women free of CHD at baseline were randomly selected into a subcohort and 3,421 CHD events were adjudicated during follow-up. Through linkage of Standard Occupational Classification codes to the Occupational Information Network, we assessed cumulative and most recent exposure of OPA. LTPA was assessed through Women's Health Initiative's physical activity questionnaire. Weighted Cox proportional hazard models were used to evaluate CHD risk. RESULTS: After adjustment for demographic and socioeconomic factors, levels of OPA were not associated with CHD risk. Compared with women with low OPA and high LTPA, women with moderate to high cumulative OPA and low LTPA had relative high CHD risk (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.26, 1.88 for moderate OPA and HR: 1.46. 95% CI: 1.20, 1.78 for high OPA). DISCUSSION: Results from this study suggest no overall association between lifetime OPA and CHD risk in women, but the impact of OPA varies by LTPA levels.