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Science ; 374(6575): 1586-1593, 2021 Dec 24.
Article in English | MEDLINE | ID: covidwho-1666355


The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to countering the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency in a phase 1 clinical trial in healthy human participants.

COVID-19/drug therapy , Lactams/pharmacology , Lactams/therapeutic use , Leucine/pharmacology , Leucine/therapeutic use , Nitriles/pharmacology , Nitriles/therapeutic use , Proline/pharmacology , Proline/therapeutic use , SARS-CoV-2/drug effects , Viral Protease Inhibitors/pharmacology , Viral Protease Inhibitors/therapeutic use , Administration, Oral , Animals , COVID-19/virology , Clinical Trials, Phase I as Topic , Coronavirus/drug effects , Disease Models, Animal , Drug Therapy, Combination , Humans , Lactams/administration & dosage , Lactams/pharmacokinetics , Leucine/administration & dosage , Leucine/pharmacokinetics , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Nitriles/administration & dosage , Nitriles/pharmacokinetics , Proline/administration & dosage , Proline/pharmacokinetics , Randomized Controlled Trials as Topic , Ritonavir/administration & dosage , Ritonavir/therapeutic use , SARS-CoV-2/physiology , Viral Protease Inhibitors/administration & dosage , Viral Protease Inhibitors/pharmacokinetics , Virus Replication/drug effects
Int Nurs Rev ; 68(2): 256-265, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1201552


AIM: To identify the factors affecting fear, anxiety and depressive symptoms among frontline nurses working with COVID-19 patients or are in charge of COVID-19 screening in Korea. BACKGROUND: Nurses are at a higher risk of COVID-19 infection because they are in closer, longer-duration contact with patients. These situations can negatively affect the mental health of nurses. METHODS: This study analysed data from COVID-19 module in the Korean Nurses' Health Study. Data from 906 participants were analysed. To identify the factors influencing mental health, descriptive statistics, Pearson's correlation and hierarchical multiple regression analyses were performed. RESULTS: Caring for patients who are COVID-19-positive increased levels of fear, anxiety and depressive symptoms of nurses. The hospital safety climate influenced mental well-being among nurses. CONCLUSION: Caring for patients with COVID-19 had a negative impact on fear, anxiety and depressive symptoms. However, the higher was the perceived hospital safety climate, the lower were the nurses' psychological symptoms. Further research on the mental health of nurses is warranted. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Institutions should manage human resources to enable periodic rotation of nurses' work and working periods related to COVID-19. In addition, hospital managers should provide sufficient personal protective equipment, related education, and safety climate.

COVID-19/nursing , Mental Health , Nursing Staff, Hospital/psychology , Pneumonia, Viral/nursing , Adult , Anxiety/epidemiology , COVID-19/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Fear , Female , Humans , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Republic of Korea/epidemiology , SARS-CoV-2