Background:The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. Methods: A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acuterespiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. Results: Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16-23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubationperiod was 2 days (range, 1-4). The median serial-interval was 1 day (range, 0-4). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. Conclusions: SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.

The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.

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The bromodomain and extra-terminal domain (BET) family of proteins are readers which specifically recognize histone-acetylated lysine residues. Each BET bromodomain protein contains two highly homologous domains: the first bromodomain (BD1) and the second bromodomain (BD2). Pan-BET bromodomain inhibition is a potential therapy for various cancers and immune-inflammatory diseases, but only few reported inhibitors show selectivity within the BET family. Herein, we identified a series of benzo­[cd]­indol-2­(1H)-ones and pyrrolo­[4,3,2-de]­quinolin-2­(1H)-ones with good selectivity for BET BD1. Through structure-based optimization, highly active and selective compounds are ultimately obtained. The representative compounds are the first reported inhibitors with selectivity more than 100-fold for BRD4(1) over BRD4(2). Among them, we further show that 68 (LT052) mediates BRD4/NF-κB/NLRP3 signaling inflammatory pathways with comparable protein expression and significantly improves symptoms of gout arthritis in a rat model. Therefore, selective pharmacological modulation of individual bromodomains could represent a strategy for the treatment of acute gouty arthritis.