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We developed a fully recombinant anti-CD20 protein derived from cDNA encoding one Fab domain, two IgG1 Fc regions, the IgG2 hinge, and an isoleucine zipper. This protein, called GB4542, contained both the homodimer and higher-order multimers. Binding studies revealed that GB4542 preferentially bound CD20+ cells yet also recognized CD20−FcγR+ PBMC. In contrast, a control mAb containing the identical Fab region, GB4500, failed to bind CD20−FcγR+ PBMC. Consistent with these findings, interactions between GB4542 and the canonical FcγRs had substantially lower KD values than correlate interfaces between GB4500 and these receptors. At low concentrations, GB4542 showed enhanced Ab-dependent cellular cytotoxicity, Ab-dependent cellular phagocytosis, and complement-dependent cytotoxicity compared with GB4500. However, at higher concentrations, an Fc analog of GB4542 inhibited anti-CD20 mAb–mediated B cell clearance through direct blocking of both Fc–FcγR interactions and C1q deposition on target cells. Furthermore, the higher-order multimer fraction of GB4542 demonstrated greater binding avidity with the canonical FcγRs and was associated with inhibitory effects observed in Ab-dependent cellular phagocytosis and complement-dependent cytotoxicity assays. These data suggest that GB4542 might have utility in the treatment of autoimmune diseases by combining both mAb-mediated B cell depletion and multimerized Fc-mediated tolerogenic effects.

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Objective: To perform molecular docking of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 3CL hydrolytic enzyme (3CLpro) and Angiotensin-Converting Enzyme II (ACE2) receptors, and to seek potential natural anti-COVID-19 drugs using computer virtual screening technology. Methods: In this study, the Autodock Vina software was first used to achieve the molecular docking of the targets, namely, sars-cov-2 3CL hydrolase and ACE2. Then, the herbals acting on 3CLpro and ACE2 receptors were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the active ingredients were also selected. After that, the chemical-target network was constructed based on the network pharmacology, and the functional enrichment analysis of Gene Ontology (GO) and the pathway enrichment analysis of Kyoto Gene and Genome Encyclopedia (KEGG) were carried out by DAVID to speculate about the mechanism of action of the core drug. Results: A total of six potential anti-COVID-19 active ingredients were selected from natural herbs. They were evaluated by the “ADME” and "Lipinski” rules and their content in the natural herbs were determined by the literature mining method. Finally, Bicuculline was selected as the anti-covid-19 candidate drug. Conclusion: Bicuculline has a stronger ability to combine with 3CLpro and ACE2 than chemical drugs recommended in the clinical practice. Internet pharmacological analysis confirms that Bicuculline can effectively resist COVID-19 pneumonia through multiple pathways.