id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-315415-3aotsb2g	Dong, Jianbo	Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2	2020-10-20		.txt	text/plain	7194	427	57	In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19. (c) The binding of VHH-Fcs and ACE2 to Expi293 cells expressing SARS-CoV-2 S1 wild type (WT) or mutant proteins (del1-del5) were assessed by flow cytometry following FITC-conjugated secondary antibody treatment. Based on the binding and epitope binning data, we constructed 3D docking models that predicted the interactions between SARS-CoV-2 S1 RBD, ACE2 and lead VHH-Fcs (Fig. 2e) . Next, we tested whether the combination of individual VHHs binding to different S1 RBD epitopes into bi-specific antibody molecules would yield synergistic effects in SARS-CoV-2 binding and S/ACE2 blocking.	./cache/cord-315415-3aotsb2g.txt	./txt/cord-315415-3aotsb2g.txt