Author: Raoul, Hervé ; Liu, Caixuan ; Bi, Yuhai ; Zhao, Yapei ; Yao, Hebang ; Cong, Yao ; Bao, Juan ; Rockx, Barry ; GeurtsvanKessel, Corine H ; Gong, Yuhuan ; van Vlissingen, Martje Fentener ; Tian, Xiao-Xu ; Qin, Wenming ; Zhang, Ning ; Lan, Jiaming ; Cai, Hongmin ; Zhou, Bingjie ; Han, Wenyu ; Lavillette, Dimitri ; Richard, Audrey S ; Wang, Yifan ; Wong, Gary ; Li, Tingting ; Kuo, Shu-Ming ; Hutter, Cedric A J ; Peng, Chao ; Kuiken, Thijs ; Wang, Yanxing ; Shen, Quan ; Lai, Yanling ; Li, Dianfan ; Seeger, Markus A

SARS-CoV-2, the causative agent of COVID-19¹, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein^1-6. Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics^7-17. Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability. Here, we report the rapid selection of 99 synthetic nanobodies (sybodies) against RBD by in vitro selection using three libraries. The best sybody, MR3 binds to RBD with high affinity (K_D = 1.0 nM) and displays high neutralization activity against SARS-CoV-2 pseudoviruses (IC₅₀ = 0.42 μg mL^-1). Structural, biochemical, and biological characterization suggests a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency have been generated by structure-based design, biparatopic construction, and divalent engineering. Two divalent forms of MR3 protect hamsters from clinical signs after live virus challenge and a single dose of the Fc-fusion construct of MR3 reduces viral RNA load by 6 Log₁₀. Our results pave the way for the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid development of targeted medical interventions during an outbreak.

Frontiers in Pharmacology

Use of the BRANT-MERQS scoring table for the quality assessment of type 3 medication review in patients with rheumatoid arthritis and those with type 2 diabetes mellitus

Article

Author: Steurbaut, Stephane ; Puttemans, Margot ; De Meyer, Guido R. Y. ; De Meyer, Guido R Y ; Robberechts, Anneleen ; Stas, Kaat ; Poppe, Laura ; De Loof, Hans

BackgroundA type 3 medication review (MR3) is a patient-centred medication service primarily provided by pharmacists and is presently employed routinely in several countries. In this process, pharmacists interview patients and collaborate with the treating physician to optimize the patient’s pharmacotherapy, taking into account the patient’s medication history and other medical data including laboratory values. The need to maintain the quality of such interventions during and after their initial implementation cannot be overstated.AimThe objective of this study was to refine and assess a scoring table to evaluate the quality of MR3 conducted in Belgian community pharmacies.MethodsThe comprehensive quality of MR3s was assessed by scoring its various components using a previously developed scoring table, called BRANT-MERQS, Brussels Antwerp Medication Review Quality Score. MR3s were analysed from an implementation study with patients suffering from rheumatoid arthritis (RA, subproject 1) and type 2 diabetes mellitus (T2DM, subproject 2). Additional information was obtained during a telephone call with a subset of participating pharmacists of subproject 1 who finalized their first MR3.ResultsIn subproject 1, a total of 21 MR3s of patients with RA were examined. The assessment showed favourable scores for elements such as a well-organized medication schedule, treatment adherence, and the elaboration of specific interventions. However, certain other quality criteria posed challenges in the evaluation, for example, the use of simple and understandable language. Pharmacists faced time constraints, and elderly general practitioners (GPs) displayed limited enthusiasm, which were notable barriers observed for this subproject. In the context of subproject 2 that investigated 41 MR3s in patients with T2DM, the quality criteria of interaction between pharmacist and GP, and used sources and tools received high scores. However, there was still room for improvement, especially in areas such as accurate dosing, handling kidney function, QT prolongation, correctly associating laboratory values with relevant drugs and medical conditions, and optimisation of medication schedules for patients.ConclusionThis study demonstrated the feasibility of MR3 quality assessment through a scoring system. However, it also unveiled the tool’s current imperfections and highlighted the ongoing need for refinement, something expected of a new service in an implementation phase.

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Preclinical	CN	Center for Excellence and Innovation in Molecular Cell Science, Chinese Academy of Sciences	30 Jul 2021

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