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1.
Proc Natl Acad Sci U S A ; 117(44): 27381-27387, 2020 11 03.
Article in English | MEDLINE | ID: covidwho-867659

ABSTRACT

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and thus repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (Mpro). The accurate FEP-ABFE predictions were based on the use of a restraint energy distribution (RED) function, making the practical FEP-ABFE-based virtual screening of the existing drug library possible. As a result, out of 25 drugs predicted, 15 were confirmed as potent inhibitors of SARS-CoV-2 Mpro The most potent one is dipyridamole (inhibitory constant Ki = 0.04 µM) which has shown promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (Ki = 0.36 µM) and chloroquine (Ki = 0.56 µM) were also found to potently inhibit SARS-CoV-2 Mpro We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Drug Repositioning , Protease Inhibitors/pharmacology , Viral Nonstructural Proteins/antagonists & inhibitors , Chloroquine/pharmacology , Coronavirus Infections/drug therapy , Cysteine Endopeptidases , Dipyridamole/pharmacology , Humans , Hydroxychloroquine/pharmacology , Molecular Docking Simulation , Molecular Structure , Pandemics , Pneumonia, Viral/drug therapy
2.
Nat Immunol ; 21(9): 1107-1118, 2020 09.
Article in English | MEDLINE | ID: covidwho-710376

ABSTRACT

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.


Subject(s)
Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , Betacoronavirus/immunology , Coronavirus Infections/immunology , Interferon Type I/metabolism , Pneumonia, Viral/immunology , Receptors, Immunologic/metabolism , Adolescent , Adult , Aged , Antigens, CD/genetics , Antigens, CD/immunology , Antigens, Differentiation, T-Lymphocyte/genetics , Antigens, Differentiation, T-Lymphocyte/immunology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Female , GPI-Linked Proteins/genetics , GPI-Linked Proteins/immunology , GPI-Linked Proteins/metabolism , Humans , Interferon Type I/genetics , Interferon Type I/immunology , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , RNA-Seq , Receptors, Immunologic/genetics , Receptors, Immunologic/immunology , Severity of Illness Index , Single-Cell Analysis
3.
Ann Palliat Med ; 9(4): 2171-2177, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-660262

ABSTRACT

BACKGROUND: Novel coronavirus pneumonia (COVID-19) has become a global pandemic. However, a technical standard for oxygen therapy nursing, as well as how this would improve clinical outcomes and symptoms, is yet to be explored. METHODS: From February 9, 2020, to March 31, 2020, 58 patients of confirmed COVID-19 were admitted to the 20th ward of the Eastern Branch, Renmin Hospital of Wuhan University. Fifteen patients who did not receive oxygen therapy and 13 patients who were transferred from other hospitals were excluded. The rest of the 30 patients that received standardized oxygen therapy in our unit were included in the study. Baseline characteristics, symptoms, and finger pulse oxygen saturation were collected during hospitalization. RESULTS: Clinical outcomes of the 30 patients were as follows: 27 patients (90.00%) were cured and discharged; 3 patients (10.00%) who continued to stay in hospital were stabilized with symptoms relieved. The fingertip oxygen saturation was 94.80%±3.49% at ICU admission and 97.8%±1.27% when transferred out of ICU after standardized oxygen therapy (P<0.005). The symptoms of dyspnea, fatigue, and muscle aches of the patients were improved when transferred out of ICU, compared with their condition when admitted to ICU (P<0.05). CONCLUSIONS: The standardized oxygen therapy nursing strategy for patients with COVID-19 emphasizes the nursing measurement, which focuses on the patient's oxygenation. It is led by nurses and starts oxygen therapy at an earlier stage. It not only improves the clinical outcomes of critical patients but also effectively reduces the infection risk of medical staff while emphasizing nursing quality management.


Subject(s)
Coronavirus Infections/therapy , Oxygen Inhalation Therapy/nursing , Oxygen Inhalation Therapy/standards , Pneumonia, Viral/therapy , Aged , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/nursing , Female , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/nursing , Treatment Outcome
4.
Ann Palliat Med ; 9(3): 1198-1205, 2020 May.
Article in English | MEDLINE | ID: covidwho-530660

ABSTRACT

BACKGROUND: Nursing quality is an integral part of health care quality and one of key performance indicators (KPIs) for health care management. The Plan-Do-Check-Act (PDCA) cycle is a management tool for continuous improvement of a business's products or processes. It can be applied to standardize nursing management and thus improve the nursing quality and increase the survival rate of patients. This study assessed the value of the PDCA cycle in standardizing nursing management in an intensive care unit (ICU) for patients with severe coronavirus disease 2019 (COVID-19). METHODS: The status quo of the ICU was analyzed, and the relevant issues and countermeasures were proposed. The PDCA cycle was applied to standardize the nursing management in the ICU. RESULTS: Nine measures were proposed and applied to improve the management of the COVID-19 ICU: defining the clean or contaminated areas, use of self-designed shoe storage cabinets, defining staff roles and responsibilities, establishing the staffing structure, staff training, placing items at fixed locations, improving shift handover, use of bulletin boards for listing key points, and use of reserved drugs cabinets. The virus contamination awareness, professional skills, awareness of duties and responsibilities, and quality and performance of nursing were remarkably improved 2 weeks after the implementation of the above countermeasures. CONCLUSIONS: The PDCA cycle helps to standardize nursing management in COVID-19 ICU by developing and applying effective nursing management approaches.


Subject(s)
Coronavirus Infections/nursing , Critical Care Nursing/organization & administration , Critical Care Nursing/standards , Intensive Care Units/organization & administration , Pneumonia, Viral/nursing , Quality Assurance, Health Care/methods , China/epidemiology , Coronavirus Infections/epidemiology , Humans , Nursing Administration Research , Nursing Evaluation Research , Pandemics , Pneumonia, Viral/epidemiology
5.
Acta Pharm Sin B ; 10(7): 1205-1215, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-88716

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

6.
J Nurs Manag ; 2020 Apr 07.
Article in English | MEDLINE | ID: covidwho-38429

ABSTRACT

In December 2019, several novel coronavirus infections were firstly reported in Wuhan, Hubei Province in China, and the outbreak is quickly expanding locally and globally. World Health Organization (World Health Organization, 2020a) announced the coronavirus epidemic as an "International Public Health Emergency of International Concern (PHEIC)" on January 30, 2020.

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