5-Hydroxymethylfurfural multimers induce pseudo-allergic reaction through FcεRI at high doses.

Under acidic and high temperature conditions, 5-hydroxymethylfurfural (5-HMF) converted from sugar further produces dimers (Compound II) and trimers (Compound III). The polymers were less reported, and sensitization effect of them was reported in this study. Compounds II and III induced the local and systemic anaphylaxis effect in passive cutaneous anaphylaxis mice model and activated RBL-2H3 cell inducing [Ca2+ ] mobilization, resulting in the release of ß-hexosaminidase and histamine in vitro. The gene knockdown assay figured out that Compounds II and III induced degranulation through FcεRI. Further, Compounds II and III had a certain affinity with FcεRI by cell membrane chromatography and may combine on the "proline sandwich" structure indicated by molecular docking. All above suggested Compounds II and III can induce pseudo-allergic reaction through FcεRI in vivo and in vitro. Our work provides basic research to prove that the newly discovered 5-HMF transformants, Compounds II and III, induce pseudo-allergic reaction in vitro and in vivo through FcεRI, which is different pathway from 5-HMF. In foods with high sugar content, the sensitization of Compounds II and III needs more attention. In high-sugar foods and medicines, especially traditional Chinese medicine injections, the content of transformants needs to be detected.

Screened antipsychotic drugs inhibit SARS-CoV-2 binding with ACE2 in vitro.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has swept the globe and no specific effective drug has been identified. Drug repurposing is a well-known method to address the crisis in a time-critical fashion. Antipsychotic drugs (APDs) have been reported to inhibit DNA replication of hepatitis B virus, measles virus germination, and HIV infection, along with replication of SARS-CoV and MERS-CoV, both of which interact with host cells as SARS-CoV-2. METHODS: Nineteen APDs were screened using ACE2-HEK293T cell membrane chromatography (ACE2-HEK293T/CMC). Cytotoxicity assay, coronavirus spike pseudotype virus entry assay, surface plasmon resonance, and virtual molecular docking were applied to detect affinity between ACE2 protein and drugs and a potential antiviral property of the screened compounds. KEY FINDINGS: After the CMC screening, 8 of the 19 APDs were well-retained on ACE2-HEK293T/CMC column and showed significant antiviral activities in vitro. Three quarters of them belong to phenothiazine and could significantly inhibit the entrance of coronavirus into ACE2-HEK293T cells. Aother two drugs, aripiprazole and tiapride, exhibited weaker inhibition. We selected five of the drugs for subsequent evaluation. All five showed similar affinity to ACE2 and virtual molecular docking demonstrated they bound with different amino acids respectively on ACE2 which SARS-CoV-2 binds to. SIGNIFICANCE: Eight APDs were screened for binding with ACE2, five of which demonstrated potential protective effects against SARS-CoV-2 through acting on ACE2. Although the five drugs have a weak ability to block SARS-CoV-2 with a single binding site, they may provide a synergistic effect in adjuvant therapy of COVID-19 infection.