Efficient vitamin B12-imprinted boronate affinity magnetic nanoparticles for the specific capture of vitamin B12.

Vitamin B12 (VB12) has an important function in human physiology. However, analysis of VB12 at natural levels in foods or biological samples is difficult because of its very low concentration level and the presence of high-abundance components which can interfere with the measuring system. Thus, it is essential to develop efficient and selective enrichment approaches for VB12. Molecularly imprinted polymers (MIPs) have important applications from separation and sensing to catalysis. However, there is no report on the preparation of MIPs for VB12. Here, we use boronate affinity-based oriented surface imprinting to prepare MIPs for VB12. A VB12 template was first covalently immobilized onto the surface of boronic acid functionalized magnetic nanoparticles. Subsequently, a thin imprinting coating of poly(2-anilinoethanol) was formed to cover the substrate surface via in-water polymerization. After removing the template, 3D cavities complementary to the molecular size and shape of the template were formed in the imprinting layer. The imprinting coating was highly hydrophilic and presented limited residual boronic acid, thus non-specific binding was avoided. The prepared MIPs exhibited several highly favorable features, including excellent specificity, high binding strength and low binding pH. The prepared MIPs were successfully applied to the analysis of VB12 in human milk.

The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2.

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

HTE- and AI-assisted development of DHP-catalyzed decarboxylative selenation.

1,4-Dihydropyridine (DHP) derivatives play key roles in biology, but are rarely used as catalysts in synthesis. Here, we developed a DHP derivative-catalyzed decarboxylative selenation reaction that showed a broad substrate scope, with the assistance of high-throughput experimentation (HTE) and artificial intelligence (AI). The AI-based model could identify the key structural features and give accurate prediction of unseen reactions (R2 = 0.89, RMSE = 9.0%, and MAE = 6.3%). Our work not only developed the catalytic applications of DHP derivatives, but also demonstrated the power of the combination of HTE and AI to advance chemical synthesis.

Efficient preparation of surface imprinted magnetic nanoparticles using poly (2-anilinoethanol) as imprinting coating for the selective recognition of glycoprotein.

In view of the significance of glycoprotein biomarkers for early clinical diagnostics and treatments of diseases, it is essential to develop efficient and selective enrichment approaches for glycoproteins. Molecularly imprinted polymers (MIPs) have found important applications for separation and enrichment of glycoproteins. In this study, we use boronate affinity-based controllable oriented surface imprinting to prepare glycoprotein-imprinted magnetic nanoparticles. A glycoprotein was first immobilized onto the surface of boronic acid functionalized magnetic nanoparticles by boronate affinity. Subsequently, self-polymerization of 2-anilinoethanol was carried out to form thin imprinting coating on the magnetic nanoparticles surface with appropriate thickness. After removing the template with an acidic solution containing sodium dodecyl sulfate, 3D cavities complementary to the template were efficiently formed in the imprinting layer. The imprinting coating was highly hydrophilic and presented limited residual boronic acid, thus non-specific binding was avoided. Using horseradish peroxidase as a model target, the effects of imprinting conditions on the properties and performance of the prepared MIPs were investigated. The obtained MIPs exhibited several highly favorable features, including excellent specificity, high binding strength and low binding pH. The MIPs were successfully applied to the analysis of transferrin (TRF) in human serum.