Amino Acid Sequence ; Coronavirus/drug effects* ; Coronavirus Infections/drug therapy* ; Drug Design ; Humans ; Protein Structure, Secondary ; Spike Glycoprotein, Coronavirus/metabolism* ; Viral Fusion Protein Inhibitors/pharmacology* ; Viral Fusion Proteins/metabolism*

Adult ; Betacoronavirus ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; epidemiology ; etiology ; prevention & control ; therapy ; Diagnosis, Differential ; Extracorporeal Membrane Oxygenation ; Humans ; Pandemics ; prevention & control ; Pneumonia, Viral ; epidemiology ; etiology ; prevention & control ; therapy ; Practice Guidelines as Topic ; Respiration, Artificial

Betacoronavirus ; Consensus ; Coronavirus Infections ; complications ; epidemiology ; prevention & control ; Epidemics ; Humans ; Minimally Invasive Surgical Procedures ; Musculoskeletal Diseases ; complications ; therapy ; Pandemics ; prevention & control ; Pneumonia, Viral ; complications ; epidemiology ; prevention & control

Betacoronavirus ; Clinical Protocols ; Coronavirus Infections ; diagnosis ; epidemiology ; pathology ; therapy ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; diagnosis ; epidemiology ; pathology ; therapy

Betacoronavirus ; Clinical Protocols ; Coronavirus Infections ; diagnosis ; pathology ; therapy ; transmission ; Humans ; Pandemics ; Patient Discharge ; Pneumonia, Viral ; diagnosis ; pathology ; therapy ; transmission ; Triage

Betacoronavirus ; Coronavirus Infections ; rehabilitation ; Critical Illness ; Hospitalization ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Patient Education as Topic ; Pneumonia, Viral ; rehabilitation ; Respiratory Therapy ; methods

Antiviral Agents ; therapeutic use ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Humans ; Pandemics ; Pneumonia, Viral ; drug therapy

BACKGROUND: At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.
Betacoronavirus ; drug effects ; Coronavirus Infections ; drug therapy ; Glucocorticoids ; adverse effects ; therapeutic use ; Humans ; Pandemics ; Pneumonia, Viral ; drug therapy ; Randomized Controlled Trials as Topic ; Severity of Illness Index

Adult ; Aged ; Antiviral Agents ; administration & dosage ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drug Therapy, Combination ; Humans ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Randomized Controlled Trials as Topic ; Ribavirin ; administration & dosage ; Ritonavir ; administration & dosage

BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37, t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] × 10vs. 1.00 ± 0.43, t = 3.98, P < 0.05). CONCLUSIONS Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.
Betacoronavirus ; drug effects ; genetics ; Cell Line ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; drug therapy ; Drug Approval ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; RNA, Small Interfering ; genetics ; Real-Time Polymerase Chain Reaction ; Viral Load