RESUMEN
The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.
RESUMEN
In the title compound, [Ni(C(9)H(6)N(3)O(3)S)(2)(H(2)O)(2)](n), the Ni(II) atom, located on an inversion center, is ligated in an octa-hedral geometry by two carboxyl-ate O atoms from two 2-{[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]sulfan-yl}acetate (L) ligands and two O atoms from water mol-ecules in the equatorial plane, and two pyridine N atoms from other two L ligands at the apical sites. Two L ligands bridge pairs of metal atoms in an anti-parallel manner, forming centrosymmetric dinuclear quasi-recta-ngular units which are linked into infinite double-stranded chains parallel to [100]. O-Hâ¯O hydrogen bonds between the coordinating water mol-ecules and the carboxyl-ate groups of the L ligand as well as interchain Sâ¯N inter-actions [2.726â (2)-3.363â (2)â Å] lead to the formation of a layer structure parallel to (001).
RESUMEN
In the title compound, [Mn(C(12)H(8)NO(2))(2)(H(2)O)(4)], the Mn(2+) ion lies on a twofold rotation axis and has a distorted N(2)O(4) octa-hedral coordination geometry formed by four water O atoms in the equatorial plane and two apical pyridyl N atoms. A three-dimensional network is formed in the crystal structure by multiple O-Hâ¯O hydrogen bonds between the coordin-ating water molecules and the free carboxylate groups.
