ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat due to the lack of effective drugs or vaccines against SARS-CoV-2. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. TMPRSS2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cancer cells (LNCaP) but not in human lung cancer cells or patient-derived lung organoids. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19.
ABSTRACT
Objective The study aimed to explore the relationship between organizational commit ment,leader-member exchange and nurses' organizational citizenship behavior based on an empirical study.Methods A total of 264 nurses recruited from four general hospitals were investigated with the Organizational Commitment Scale,Leader-Member Exchange Scale,and Organizational Citizenship Behavior Scale.Results Affective organizational commitment and leader-member exchange correlated with every factor of organizational citizenship behavior.Both affective organizational commitment and leader-member exchange predicted the variance of identification with organization 0.29,altruism toward colleagues 0.06,interpersonal harmony 0.09,protecting organizational resources 0.12,and conscientiousness 0.28.Conclusions Affective organizational commitment and leader-member exchange had a positive influence on nurses' organizational citizenship behavior,thus,hospital managers should strengthen nurses' affective organizational commitment and leader-member exchange to promote their organizational citizenship behaviors.
