Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor in just 10 min. A drug library of 1068 approved compounds was used to screen for SARS-CoV2 entry inhibition, and 9 active drugs were identified as specific pseudovirus entry inhibitors. A plaque reduction neutralization test using authentic SARS-CoV-2 virus in Vero E6 cells confirmed that 2 of these drugs (Etravirine and Dolutegravir) significantly inhibited the infection of SARS-CoV-2. With molecular docking, we showed that both Etravirine and Dolutegravir are preferentially bound to primary ACE2-interacting residues on the RBD domain, implying that these two drug blocks may prohibit the viral attachment of SARS-CoV-2. We compared the neutralizing activities of these entry inhibitors against different pseudoviruses carrying spike proteins from alpha, beta, gamma, and delta variants. Both Etravirine and Dolutegravir showed similar neutralizing activities against different variants, with EC50 values between 4.5 to 5.8 nM for Etravirine and 10.2 to 22.9 nM for Dolutegravir. These data implied that Etravirine and Dolutegravir may serve as general spike inhibitors against dominant viral variants of SARS-CoV-2. 相似文献
During sintering of the silica-based ceramic core of turbine blades, a phenomenon called “nonuniform sintering” occurs that negatively affects the thermal and mechanical properties of the core. Standard samples of silica-based core were prepared by an injection molding method and sintered with alumina backfilling powder with different sodium contents. The effect of sodium content on the nonuniform sintering of silica-based cores and the thermal and mechanical properties was evaluated. Results show that the sintering level and the content of α-cristobalite in the surface layer are significantly higher than that of the sample interior. A considerable number of microcracks are found in the surface layer due to the β to α-phase transition of cristobalite. As the sodium content in the alumina powder decreases, the level of the nonuniform sintering and the amount of crystallized cristobalite in the surface layer decrease, which is beneficial to the thermal expansion and flexural strength at ambient temperature. The flexural strength and thermal deformation at high temperature are improved by reducing the surface cracks, but deteriorated with the decrease of the cristobalite crystallization when the surface cracks are macroscopically invisible.