A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

The recently emerged novel coronavirus pneumonia, named the coronavirus disease 2019 (COVID-19), shares several clinical characteristics with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and spread rapidly throughout China in December of 2019 (Huang et al., 2020). The pathogen 2019 novel coronavirus (2019-nCoV) is now named SARS coronavirus 2 (SARS-CoV-2) and is highly infectious. As of Apr. 9, 2020, over 80 000 confirmed cases had been reported, with an estimated mortality rate of 4.0% (Chinese Center for Disease Control and Prevention, 2020). Person-to-person transmission and familial clustering have been reported (Chan et al., 2020; Nishiura et al., 2020; Phan et al., 2020). However, there is no evidence of fetal intrauterine infection in pregnant women who have been infected with SARS-CoV-2 in their third trimester (Chen et al., 2020). It is unclear whether breastfeeding transmits the virus from previously infected and recovered mothers to their babies. Here we report the clinical course of a pregnant woman with COVID-19. In order to determine whether SARS-CoV-2 can be transmitted to newborns through breastfeeding, we measured viral RNA in the patient's breastmilk samples at different time points after delivery.
Adult ; Betacoronavirus ; Breast Feeding ; China ; Coronavirus Infections ; diagnosis ; Female ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Milk, Human ; virology ; Pandemics ; Pneumonia, Viral ; diagnosis ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; RNA, Viral ; isolation & purification

Since the global outbreak of severe acute respiratory syndrome (SARS) in 2003, China has gradually built a robust prevention and control system for sudden infectious diseases. All large hospitals have a fever clinic that isolates patients with all kinds of acute communicable diseases as the first line of medical defense. The emergency department, as the second line of medical defense in hospitals, is constantly shouldering the heavy responsibility of screening communicable diseases while also treating all kinds of other non-communicable acute and critical diseases (Zhang et al., 2012; Zhu et al., 2015; Wang et al., 2017; Feng et al., 2018; Lu, 2018; Xu and Lu, 2019). An outbreak of pneumonia of unknown etiology that began in Wuhan city (China) has spread rapidly in China since December 2019 (Huang et al., 2020; WHO, 2020; Zhu et al., 2020). In February 2020, the National Health Commission of China named the disease a novel coronavirus pneumonia (NCP); then, it was formally named the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) on Feb. 11, 2020. The Coronavirus Study Group of the International Committee on Taxonomy of Viruses designated this causative virus as SARS coronavirus 2 (SARS-CoV-2). SARS-CoV-2 belongs to the β coronavirus genus, and its pathogenic mechanism has not been clarified, which requires further study. To better understand the clinical characteristics of COVID-19 and more effectively prevent and control this disease, we retrospectively analyzed four representative cases of COVID-19 that had recently been screened and diagnosed in our emergency department.
Adult ; Betacoronavirus ; China ; epidemiology ; Coronavirus Infections ; diagnosis ; Emergency Service, Hospital ; Female ; Humans ; Lung ; diagnostic imaging ; Male ; Middle Aged ; Pandemics ; Patient Isolation ; Pneumonia, Viral ; diagnosis ; Tomography, X-Ray Computed

We optimized a fluorescent quantitative polymerase chain reaction (qPCR) assay system for rapid and real time detection of SARS-CoV-2 RNA. The results show that the lowest dilution of RNA samples used for the detection of SARS-CoV-2 RNA could reach 1/10 000 (the initial value is set as 10 ng/μL). Moreover, the cycle threshold (Ct) for samples of clinically diagnosed COVID-19 was lower than 35 or 40. The sensitivity of this method was satisfactory. The results were consistent with those of the COVID-19 detection kit on the market under the same conditions, but the number of cycles required was shortened by about 2. Therefore, the optimized assay developed in this study can be used in screening and early clinical diagnosis. Our work provides a tool to facilitate rapid clinical diagnosis of COVID-19.
Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnosis ; virology ; Early Diagnosis ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; virology ; Polymerase Chain Reaction ; methods ; standards ; RNA, Viral ; analysis ; genetics ; Sensitivity and Specificity ; Time Factors

Betacoronavirus ; isolation & purification ; pathogenicity ; Bile Acids and Salts ; metabolism ; Bile Ducts, Intrahepatic ; pathology ; virology ; Cell Culture Techniques ; Coronavirus Infections ; complications ; pathology ; Cytokine Release Syndrome ; etiology ; physiopathology ; Cytopathogenic Effect, Viral ; Epithelial Cells ; enzymology ; pathology ; virology ; Humans ; Hyperbilirubinemia ; etiology ; Liver ; pathology ; Organoids ; pathology ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; analysis ; Pneumonia, Viral ; complications ; pathology ; Receptors, Virus ; analysis ; Serine Endopeptidases ; analysis ; Viral Load

Adolescent ; Adult ; Aged ; COVID-19/virology* ; COVID-19 Nucleic Acid Testing/methods* ; Child ; Coronavirus Nucleocapsid Proteins/genetics* ; Feces/virology* ; Female ; Humans ; Male ; Middle Aged ; Phosphoproteins/genetics* ; RNA, Viral/genetics* ; SARS-CoV-2/isolation & purification* ; Young Adult

OBJECTIVE: To investigate the clinical outcome of patients with moderate type of coronavirus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid. METHODS: Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantined in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged. During the quarantined period, the symptoms and signs were documented, and sputum or nasal swab and feces samples were collected to test SARS-CoV-2 nucleic acid by RT-PCR method. RESULTS: There was no symptoms and signs during the quarantine period in all 7 patients. However, respiratory swabs from 3 patients were confirmed positive of SARS-CoV-2 nucleic acid at 5 to 7 days after they met the discharge criteria. CONCLUSIONS There is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary.
Betacoronavirus ; isolation & purification ; Coronavirus Infections ; diagnosis ; Feces ; chemistry ; virology ; Follow-Up Studies ; Humans ; Pandemics ; Patient Discharge ; statistics & numerical data ; Pneumonia, Viral ; diagnosis ; Quarantine ; statistics & numerical data ; RNA, Viral ; analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors

OBJECTIVE: To analysis the medication characteristics of the prescriptions issued via open channel by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine in treating coronavirus disease 2019 (COVID-19). METHODS: We collected the data of traditional Chinese medicine related to treatment plans published by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine from the start of COVID-19 outbreak to February 19, 2020. The frequency analysis, cluster analysis and association analysis were performed. RESULTS: The study collected 4 national and 34 regional prevention and treatment plans, 578 items, 84 traditional Chinese formulations, 60 Chinese patent medicines, and 230 Chinese herbs. The high frequently used herbs were , and . The commonly used traditional formulations included decoction, powder, and decoction. The Chinese patent drugs included pill, injection, and capsule. The most common paired medications were and and Two core combinations and one novel formula were discovered in the study. CONCLUSIONS powder and decoction are the basic formulations for syndrome of COVID-19. In addition, decoction, powder, decoction and decoction are the basic formulations for syndrome of COVID-19. The main medication characteristics are clearing heat, entilating lung, removing toxicity and removing turbidity. It shows that removing toxicity and eliminating evil are the prescription thought in treating epidemic disease of traditional Chinese medicine.
Betacoronavirus ; isolation & purification ; Coronavirus Infections ; therapy ; Data Mining ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; therapy

Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.
Anesthesia ; Betacoronavirus ; isolation & purification ; Cesarean Section ; methods ; Coronavirus Infections ; complications ; Female ; Humans ; Infant ; Injections, Spinal ; Pandemics ; Pneumonia, Viral ; complications ; Pregnancy

OBJECTIVE: To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19). METHODS: The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. RESULTS: The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. CONCLUSIONS The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.
Betacoronavirus ; isolation & purification ; Colonic Neoplasms ; complications ; surgery ; Coronavirus Infections ; complications ; therapy ; Disease Management ; Humans ; Pandemics ; Pneumonia, Viral ; complications ; therapy ; Treatment Outcome