Highlights d 8,558 IgG1 + antigen-binding clonotypes were identified by high-throughput scRNA/VDJ-seq d 14 potent SARS-CoV-2 neutralizing antibodies were found from 60 convalescent patients d BD-368-2 showed high therapeutic and prophylactic efficacy in SARS-CoV-2-infected mice d Neutralizing antibodies can be directly selected based on predicted CDR3 H structures

SUMMARY Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.

Phase change materials (PCMs) have triggered considerable attention as candidates for solar‐thermal energy conversion. However, their intrinsic low thermal conductivity prevents the rapid spreading of heat into the interior of the PCM, causing low efficiencies in energy storage/release. Herein, anisotropic and lightweight high‐quality graphene aerogels are developed by directionally freezing aqueous suspensions of polyamic acid salt and graphene oxide to form vertically aligned monoliths, followed by freeze‐drying, imidization at 300 °C and graphitization at 2800 °C. After impregnating with paraffin wax, the resultant phase change composite (PCC) exhibits a high transversal thermal conductivity of 2.68 W m−1 K−1 and an even higher longitudinal thermal conductivity of 8.87 W m−1 K−1 with an exceptional latent heat retention of 98.7%. When subjected to solar radiation, solar energy is converted to heat at the exposed surface of the PCC. As a result of the PCC's high thermal conductivity in the thickness direction, heat can spread readily into the interior of the PCC enabling a small temperature gradient of <3.0 K cm−1 and a fast charging feature. These results demonstrate the potential for real‐time and fast‐charging solar‐thermal energy conversion using phase change materials with tailored anisotropy in their thermal properties.

Although several different flaviviruses may cause encephalitis, Japanese encephalitis virus is the most significant, being responsible for thousands of deaths each year in Asia. The structural and molecular basis of this encephalitis is not fully understood. Here, we report the cryo-electron microscopy structure of mature Japanese encephalitis virus at near-atomic resolution, which reveals an unusual “hole” on the surface, surrounded by five encephalitic-specific motifs implicated in receptor binding. Glu138 of E, which is highly conserved in encephalitic flaviviruses, maps onto one of these motifs and is essential for binding to neuroblastoma cells, with the E138K mutation abrogating the neurovirulence and neuroinvasiveness of Japanese encephalitis virus in mice. We also identify structural elements modulating viral stability, notably Gln264 of E, which, when replaced by His264 strengthens a hydrogen-bonding network, leading to a more stable virus. These studies unveil determinants of neurovirulence and stability in Japanese encephalitis virus, opening up new avenues for therapeutic interventions against neurotropic flaviviruses.