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Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Engineered soluble trimeric ACE2 constructs with intact enzymatic activity and high affinity to SARS-CoV-2 spike are shown to inhibit viral infection in cellular assays.

Three-dimensional DNA origami constructs can be used to deliver vaccine antigens in a multi-valent form. Here the authors design a DNA origami system for SARS-CoV-2 proteins and characterize in mice the immune response and protective capacity of generated antibodies, finding that the construct itself is not immunogenic.

The E3 ligase TRIM43 ubiquitinates the centrosomal protein pericentrin, targeting it for proteasomal degradation, leading to alterations of the nuclear lamina that repress active viral chromatin states of a range of herpesviruses.

Substitutions in SARS-CoV-2 spike protein present in the B.1.351 variant first detected in South Africa, when expressed in pseudoviruses, mediate escape from neutralization by monoclonal antibodies under clinical development and by plasma from individuals previously infected with SARS-CoV-2, but do not prevent binding of convalescent plasma to recombinant spike protein containing B.1.351 lineage substitutions.

Seder and colleagues show that mucosal adenoviral-vectored vaccine boosting durably prevents infection in nonhuman primates of the highly transmissible, heterologous XBB.1.16 strain of SARS-CoV-2.

Here, Li et al. perform a genome-wide CRISPR screen to identify host dependency factors for influenza A virus infection and show that the host mRNA cap methyltransferase CMTR1 is important for viral cap snatching and that it affects expression of antiviral genes.

In this Review, Chen, Farzan and Choe discuss our current understanding of the structure and function of the SARS-CoV-2 spike protein, the molecular mechanism of viral entry and the emergence of new variants, as well as the implications of these insights for development of spike protein-related intervention strategies.

The new entry inhibitor eCD4-Ig, consisting of the immunoadhesin form of CD4 (CD4-Ig) fused to a small CCR5-mimetic sulfopeptide, avidly binds two highly conserved sites of the HIV-1 Env protein; the inhibitor has high potency and breadth and can neutralize 100% of a diverse panel of neutralization-resistant HIV-1 viruses, and when delivered to macaques using an adeno-associated virus vector, it can provide effective long-term protection from multiple challenges with simian/human immunodeficiency virus.

The B-cell receptor of primary mouse B cells can be engineered to affinity mature an HIV-1-entry inhibitor in vivo.

Neutralisation assays are key to understanding immune responses to SARS-CoV-2 infection or vaccination. Here, the authors report a surrogate virus neutralization assay called Neu-SATiN, which measures neutralization directly from sera, and allows easy adaptation to variant-specific testing.

T cell responses to spike protein from the SARS-CoV-2 Omicron variant (B.1.1.529) are broadly similar to the responses to ancestral, Beta (B.1.351) and Delta (B.1.617.2) spike protein in vaccinated, infected and unvaccinated individuals.

A pan-betacoronavirus vaccine will likely require the elicitation of antibodies against spike regions conserved across diverse coronaviruses. Here, authors computationally engineer and experimentally validate immunogens to elicit antibodies against two such spike regions.

Cryo-EM analyses of the initial contact of the HIV-1 Env trimer with the CD4 receptor reveal that CD4 interacts with two gp120 protomers; these quaternary contacts are important for viral infectivity.

Zhang, Tang, Gao et al. report structural and functional properties of the Omicron BA.2 spike protein, and replication kinetics of the virus. Their results suggest that both immune evasion and replicative advantage may contribute to the heightened transmissibility.

A single dose of an adeno-associated virus vector encoding an HIV-1 broadly neutralizing antibody given shortly after birth results in persistent antibody expression and protection from infection in rhesus macaque models of human HIV-1 transmission through breastfeeding and sexual intercourse.

SARS-CoV-2 variants with spike (S)-protein D614G mutations currently predominate globally. Here, Zhang et al. hypothesize that D614G variant may increase infectivity by increasing S protein abundance on the virion since pseudoviruses carrying S-G614 incorporate higher amounts of S protein and enter cells more efficiently than those carrying S-D614.

Mouse B cells can be reprogrammed via Cas12a to express human antibodies that when affinity-matured in recipient mice generate broader and more potent antibody variants.

Recent interest in identifying interferon-stimulated genes that have activity against a wide range of viruses has advanced our understanding of the IFIT and IFITM families and shown the many mechanisms by which host factors can restrict viral replication.

By integrating DNA genotype and RNA sequencing data from human samples, d’Escamard et al. identify a gene regulatory co-expression supernetwork that plays an important role in fibromuscular dysplasia, a poorly understood disease affecting 3–5% of adult females.

IFITM3 shifts upon phosphorylation from acting as an antiviral effector to being a scaffold for PIP3 and thereby amplifies PI3K signalling, which can be co-opted for malignant transformation in B cell leukaemia and lymphoma.

Cpf1 is a CRISPR effector protein that exhibits greater genome editing specificity than Cas9 nuclease. Cpf1 from two distinct bacteria selectively processes RNA polymerase II transcripts into crRNA fragments competent for genome editing.

In this study, the authors report the development of an inhalable IgM-like ACE2 and show that it broadly neutralizes SARS-CoV-2 variants, lowers viral loads and lung pathology in hamsters when administered early, and has good safety profiles in rats and monkeys.

Bacteria are taught to incorporate a key mediator of protein-protein interactions.

New World hemorrhagic fever arenaviruses are rodent transmitted agents that cause severe, often fatal human disease. The structure of the Machupo virus glycoprotein 1 subunit in complex with its human cellular receptor, transferrin receptor 1, was solved. The interaction interfaces between the two proteins and sequence alignments suggest that these viruses fortuitously acquired the ability to bind human transferrin receptor 1 while adapting to their natural hosts.

Including participants from 45 countries, Bago et al. find that the situational factors that affect moral reasoning are shared across countries, with diminished observed cultural variation.

Antidepressant drugs are the most common treatment for depressive episodes but only a fraction of patients experience adequate response. Here the authors find dysregulation of miRNAs in peripheral blood samples from depressed patients after antidepressant treatment, and show that the miRNAs are regulators of psychiatrically relevant signalling pathways.

Single-molecule fluorescence resonance energy transfer imaging of conformational states of HIV-1 envelope glycoprotein trimers on intact virus and of trimers used in previous structural studies reveal the latter as downstream—rather than pre-triggered—conformations.

In vivo control of expression levels of AAV-delivered genes is enabled by an engineered RNA switch.

An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.

The DR isotype of the human leukocyte antigen of the MHC class II—or its homologues in bats, pigs, mice and chickens—is an essential cell entry determinant for bat influenza A viruses.

Entry of SARS-CoV-2 into host cells is mediated by the interaction between the viral spike protein and its receptor angiotensin-converting enzyme 2, followed by virus–cell membrane fusion. Worldwide research efforts have provided a detailed understanding of this process at the structural and cellular levels, enabling successful vaccine development for a rapid response to the COVID-19 pandemic.

An analysis of single-cell transcriptomics datasets from different tissues shows that ACE2 and TMPRSS2 are co-expressed in respiratory, corneal and intestinal epithelial cell populations, and that respiratory expression of ACE2 is associated with genes involved in innate immunity.

The cell adhesion molecule Mxra8 is identified as a receptor for multiple arthritogenic alphaviruses such as chikungunya virus, and anti-Mxra8 monoclonal antibodies are shown to reduce rates of chikungunya virus infection in mice and a range of human cells.