Highlights d MXRA8 has two Ig-like domains with an unexpected structural topology d MXRA8 binds in the ''canyon'' between two protomers of the CHIKV E spike d Both the two domains and hinge region of MXRA8 are involved in interaction d The stalk region of MXRA8 is critical for CHIKV virus entry

Safe, efficacious, and deployable vaccines are urgently needed to control COVID-19 in the large-scale vaccination campaigns. We report here the preclinical studies of an approved protein subunit vaccine against COVID-19, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and non-human primates, and elicited balanced T H 1/T H 2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 μg or 50 μg ZF2001 prevented infection with SARS-CoV-2 in lung, trachea, and bronchi, with milder lung lesions. No evidence of disease enhancement was observed in both animal models. ZF2001 has been approved for emergency use in China, Uzbekistan, Indonesia, and Columbia. The high safety, immunogenicity, and protection efficacy in both mice and NHPs found in this preclinical study was consistent with the results in human clinical trials.

Recent outbreak of flavivirus Zika virus (ZIKV) in America has urged the basic as well as translational studies of this important human pathogen. The nonstructural protein 5 (NS5) of the flavivirus has an N-terminal methyltransferase (MTase) domain that plays critical roles in viral RNA genome capping. The null mutant of NS5 MTase is lethal for virus. Therefore, NS5 is a potential drug target for the treatment of Zika virus infection. In this study, we determined crystal structures of the ZIKV MTase in complex with GTP and RNA cap analogue GpppA. Structural analyses revealed highly conserved GTP/cap-binding pocket and S-adenosylmethionine (SAM)-binding pocket. Two conformations of the second base of the cap were identified, which suggests the flexibility of RNA conformation. In addition, the ligand-binding pockets identified a continuous region of hotspots suitable for drug design. Docking calculation shows that the Dengue virus inhibitor compound 10 may bind to the ZIKV MTase.

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.Author summaryIn this study, we compared SARS-CoV-2 populations of 13 Chinese COVID-19 patients. Those viral populations contained a considerable proportion of viral sub-genomic messenger RNAs (sgmRNA), reflecting an active viral replication activity in the respiratory tract tissues. The comparison of 66 identified intra-host variants further showed a low viral genetic distance between intra-household patients and a narrow transmission bottleneck size. Despite the co-existence of genetically distinct viruses within the same host, most intra-host minor variants were not shared between transmission pairs, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Furthermore, the narrow bottleneck and active viral activity in the respiratory tract show that the passage of a small number of virions can cause infection. Our data have therefore delivered a key genomic resource for the SARS-CoV-2 transmission research and enhanced our understanding of the evolutionary dynamics of SARS-CoV-2.

Let L be an exact Lagrangian submanifold of a cotangent bundle T * M , asymptotic to a Legendrian submanifold Λ ⊂ T ∞ M . We study a locally constant sheaf of ∞-categories on L, called the sheaf of brane structures or Brane L . Its fiber is the ∞category of spectra, and we construct a Hamiltonian invariant, fully faithful functor from Γ(L, Brane L ) to the ∞-category of sheaves of spectra on M with singular support in Λ. CONTENTS 1. Introduction 1 2. Sheaves of spectra 9 3. Wavefronts, brane structures, and Nadler-Zaslow 20 References 34

Let X be a compact complex manifold, $D_c^b(X)$ be the bounded derived category of constructible sheaves on $X$, and $Fuk(T^*X)$ be the Fukaya category of $T^*X$. A Lagrangian brane in $Fuk(T^*X)$ is holomorphic if the underlying Lagrangian submanifold is complex analytic in $T^*X_{\mathbb{C}}$, the holomorphic cotangent bundle of $X$. We prove that under the quasi-equivalence between $D^b_c(X)$ and $DFuk(T^*X)$ established in [NaZa09] and [Nad09], holomorphic Lagrangian branes with appropriate grading correspond to perverse sheaves.Comment: Significant improvement of the previous version. Comments are welcome

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