Archives of toxicology
Authors: Zhao Y, Magaña LC, Cui H, Huang J, McHale CM, Yang X, Looney MR, Li R, Zhang L
Volume 17 of Issue 1 | Nature chemical biology
Authors: Bracken CJ, Lim SA, Solomon P, Rettko NJ, Nguyen DP, Zha BS, Schaefer K, Byrnes JR, Zhou J, Lui I, Liu J, Pance K, QCRG Structural Biology Consortium, Zhou XX, Leung KK, Wells JA
Neutralizing agents against SARS-CoV-2 are urgently needed for the treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domains toward neutralizing epitopes. We constructed a VH-phage library and targeted the angiotensin-converting enzyme 2 (ACE2) binding interface of the SARS-CoV-2 Spike receptor-binding domain (Spike-RBD). Using a masked selection approach, we identified VH binders to two non-overlapping epitopes and further assembled these into multivalent and bi-paratopic formats. These VH constructs showed increased affinity to Spike (up to 600-fold) and neutralization potency (up to 1,400-fold) on pseudotyped SARS-CoV-2 virus when compared to standalone VH domains. The most potent binder, a trivalent VH, neutralized authentic SARS-CoV-2 with a half-maximal inhibitory concentration (IC) of 4.0 nM (180 ng ml). A cryo-EM structure of the trivalent VH bound to Spike shows each VH domain engaging an RBD at the ACE2 binding site, confirming our original design strategy.
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Authors: Pudil R, Mueller C, Celutkiene J, Henriksen PA, Lenihan D, Dent S, Barac A, Stanway S, Moslehi J, Suter TM, Ky B, Šterba M, Cardinale D, Cohen-Solal A, Tocchetti CG, Farmakis D, Bergler-Klein J, Anker MS, Von Haehling S, Belenkov Y, Iakobishvili Z, Maack C, Ciardiello F, Ruschitzka F, Coats AJS, Seferovic P, Lainscak M, Piepoli MF, Chioncel O, Bax J, Hulot JS, Skouri H, Hägler-Laube ES, Asteggiano R, Fernandez TL, de Boer RA, Lyon AR
International journal of environmental research and public health
Authors: Nguyen N, Holmes LM, Kim M, Ling PM
Maternal health, neonatology and perinatology
Authors: Kassem Z, Sitarik A, Levin AM, Lynch SV, Havstad S, Fujimura K, Kozyrskyj A, Ownby DR, Johnson CC, Yong GJM, Wegienka G, Cassidy-Bushrow AE
Annals of internal medicine
Authors: Lo B, Sim I
JMIR public health and surveillance
Authors: Younis J, Freitag H, Ruthberg JS, Romanes JP, Nielsen C, Mehta N
Behaviour research and therapy
Authors: Holder N, Shiner B, Li Y, Madden E, Neylan TC, Seal KH, Lujan C, Patterson OV, DuVall SL, Maguen S
Volume 7 of Issue 1 | HeartRhythm case reports
Authors: Zhang X, Fan D, Srivatsa UN, Oesterle A
ESC heart failure
Authors: Ärnlöv J, Sang Y, Ballew SH, Vaidya D, Michos ED, Jacobs DR, Lima J, Shlipak MG, Bertoni AG, Coresh J, Blaha M, Post WS, Matsushita K
