简介：AbstractBackground:Medicines for the treatment of 2019-novelcoronavirus(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 ofcoronavirusdisease 2019 (COVID-19) in a 2019-nCoV-relatedcoronavirusmodel.Methods:A 2019-nCoV-related pangolincoronavirusGX_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 pangolincoronavirusmodel 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 ofcoronavirusGX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhanhu-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] × 10-4vs. 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] × 10-4vs. 1.00 ± 0.43, t= 3.98, P < 0.05).Conclusions:Our pangolincoronavirusGX_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.

简介：AbstractHumancoronavirus(HCoV) causes potentially fatal respiratory disease. Pregnancy is a physiological state that predisposes women to viral infection. In this review, we aim to present advances in the pathogenesis, clinical features, diagnosis, and treatment in HCoV in pregnancy. We retrieved information from the Pubmed database up to June 2020, using various search terms and relevant words, including coronaviruses, severe acute respiratory syndromecoronavirus, Middle East respiratory syndromecoronavirus, 2019coronavirusdisease, and pregnancy. Both basic and clinical studies were selected. We found no evidence that pregnant women are more susceptible to HCoV infection or that those with HCoV infection are more prone to developing severe pneumonia. There is also no confirmed evidence of vertical mother-to-child transmission of HcoV infection during maternal HCoV infection. Those diagnosed with infection should be promptly admitted to a negative-pressure isolation ward, preferably in a designated hospital with adequate facilities and multi-disciplinary expertise to manage critically ill obstetric patients. Antiviral treatment has been routinely used to treat pregnant women with HCoV infection. The timing and mode of delivery should be individualized, depending mainly on the clinical status of the patient, gestational age, and fetal condition. Early cord clamping and temporary separation of the newborn for at least 2 weeks is recommended. All medical staff caring for patients with HCoV infection should use personal protective equipment. This review highlights the advances in pathogenesis, maternal-fetal outcome, maternal-fetal transmission, diagnosis and treatment in HCoV including severe acute respiratory syndromecoronavirus, Middle East respiratory syndromecoronavirus, andcoronavirusdisease 2019 in pregnancy.

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简介：SincetheoutbreakofaSARSepidemiclastyear,significantadvanceshavebeenmadeonourunderstandingofthemechanismsofinteractionbetweentheSARScoronavirus(CoV)andtheimmunesystem.StronghumoralresponseshavebeenfoundinmostpatientsfollowingSARS-CoVinfection,withhightitersofneutralizingAbspresentintheirconvalescentsera.Thenucleocapsid(N)andspike(S)proteinsofSARS-CoVappeartobethedominantantigensrecognizedbyserumAbs.CD4+TcellresponsesagainsttheNproteinhavebeenobservedinSARSpatientsandanHLA-A2-restrictedcytotoxicTlymphocyteepitopeintheSproteinhasbeenidentified.ItislikelythattheimmuneresponsesinducedbySARS-CoVinfectioncouldalsocausepathologicaldamagetothehost,especiallyinthecaseofproinflammatorycytokines.ThereisalsoevidencesuggestingthatSARS-CoVmightbeabletodirectlyinvadecellsoftheimmunesystem.OurunderstandingontheinteractionbetweenSARS-CoV,theimmunesystemandlocaltissuesisessentialtofuturediagnosis,controlandtreatmentofthisverycontagiousdisease.

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简介：AbstractWith the outbreak of thecoronavirusdisease 2019 (COVID-19) pandemic, the importance of vaccines in epidemic prevention and public health has become even more obvious than ever. However, the emergence of multiple severe acute respiratory syndromecoronavirus2 variants worldwide has raised concerns about the effectiveness of current COVID-19 vaccines. Here, we review the characteristics of COVID-19 vaccine candidates in five platforms and the latest clinical trial results of them. In addition, we further discuss future directions for the research and development of the next generation of COVID-19 vaccines. We also summarize the serious adverse events reported recently after the large-scale vaccination with the current COVID-19 vaccines, including the thromboembolism caused by the AstraZeneca and Johnson & Johnson vaccines.

简介：AbstractBackground:The 2019 novelcoronavirus(2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak.Methods:Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens.Results:None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea.Conclusions:The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.