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The current COVID-19 pandemic, caused by a novel coronavirus SARS-CoV-2, poses serious threats to public health and social stability, calling for urgent need for vaccines and therapeutics. SARS-CoV-2 is genetically close to SARS-CoV, thus it is important to define the between antigenic cross-reactivity and neutralization. In this study, we firstly analyzed 20 convalescent serum samples collected from SARS-CoV infected individuals during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor-binding domain (RBD) of SARS-CoV, cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2, and neutralized both SARS-CoV and SARS-CoV-2 S protein-driven infections. Multiple panels of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV were also characterized, verifying the cross-reactive neutralization against SARS-CoV-2. Interestingly, we found that a palm civet SARS-CoV-derived RBD elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing a strategy to develop a universe vaccine against emerging CoVs. SummarySerum antibodies from SARS-CoV infected patients and immunized animals cross-neutralize SARS-CoV-2 suggests strategies for universe vaccines against emerging CoVs.
RESUMO
The coronavirus disease COVID-19, caused by emerging SARS-CoV-2, has posed serious threats to global public health, economic and social stabilities, calling for the prompt development of therapeutics and prophylactics. In this study, we firstly verified that SARS-CoV-2 uses human ACE2 as a cell receptor and its spike (S) protein mediates high membrane fusion activity. Comparing to that of SARS-CoV, the heptad repeat 1 (HR1) sequence in the S2 fusion protein of SARS-CoV-2 possesses markedly increased -helicity and thermostability, as well as a higher binding affinity with its corresponding heptad repeat 2 (HR1) site. Then, we designed a HR2 sequence-based lipopeptide fusion inhibitor, termed IPB02, which showed highly poent activities in inibibiting the SARS-CoV-2 S protein-mediated cell-cell fusion and pseudovirus infection. IPB02 also inhibited the SARS-CoV pseudovirus efficiently. Moreover, the strcuture and activity relationship (SAR) of IPB02 were characterzized with a panel of truncated lipopeptides, revealing the amino acid motifs critical for its binding and antiviral capacities. Therefore, the presented results have provided important information for understanding the entry pathway of SARS-CoV-2 and the design of antivirals that target the membrane fusion step.
RESUMO
Aim To investigate the effect of salvianolic acid B (Sal B)on c-Jun N-terminal kinase (JNK)ac-tivation and apoptosis of INS-1 cells induced by inter-mittent high glucose.Methods INS-1 cells were pre-incubated with Sal B for 24 h,followed by exposure to intermittent high glucose (IHG,11.1 mmol·L-1 12 h,33. 3 mmol·L-1 12 h)for 72 h.Cell viability was assessed by MTT assay and cell apoptosis was evalua-ted by flow cytometry.Glucose induced insulin secre-tion capacity and intracellular reactive oxygen species (ROS)contents were measured by enzyme linked im-munosorbent assay (ELISA)and a fluorescent probe DCFH-DA,respectively.Levels of JNK activation and PDX-1 protein expression were determined by Western blot analysis.Results Sal B significantly alleviated IHG-induced cell injury and apoptosis,with glucose induced insulin secretion capacity improved evidently (P<0.05 or P<0.01).Preincubation with Sal B no-tably decreased intracellular ROS and JNK activation in INS-1 cells,while the level of PDX-1 protein was in-creased markedly (P<0.05 or P<0.01 ).Conclu-sion Sal B is capable of ameliorating IHG-induced cell injury and apoptosis in INS-1 cells,which might be derived from suppression of JNK activation and up-regulation of PDX-1 protein expression.
