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Improved vaccines and antivirals are needed for many enveloped viruses. Here, the authors identify sulfur-based small molecules that disrupt viral membrane properties, inhibiting fusion and entry, and safely inactivate influenza virus. The resulting inactivated influenza vaccine is protective in mice.

Using pancreatic organoids, Lee et al. show that the balance between epithelial tissue permeability-driven lumenal pressure and cell proliferation affects ductal morphogenesis.

CD388 is a first-in-class antiviral drug–Fc conjugate engineered for extended half-life that demonstrates potent prophylactic and therapeutic efficacy against lethal influenza A and B challenge in mice.

The authors describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. They identify five mAbs that potently neutralized the majority of H5 clades and protected against lethal 2.3.4.4b H5N1 infection in mice.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

A massively parallel computational and experimental approach for de novo designing and screening small hyperstable proteins targeting influenza haemagglutinin and botulinum neurotoxin B identifies new therapeutic candidates more robust than traditional antibody therapies.

Despite their essentiality, human ANP32A and ANP32B are redundant host factors for influenza virus genome replication. In this work, authors show that an influenza virus grown in cells lacking ANP32A and ANP32B evolved to use ANP32E. They explore the polymerase mutations that enable this, and demonstrate increased virulence in mice.

Cells can form a rotating doublet. This rotation is driven by the symmetry breaking of myosin polarization in the cortices of the two cells.

Machine learning methods for molecule predictions use various representations of molecules such as in the form of strings or graphs. As an extension of graph representation learning, Probst and colleagues propose to represent a molecule as a set of atoms, to better capture the underlying chemical nature, and demonstrate improved performance in a range of machine learning tasks.

In this study, the authors report the small molecule inhibitor EDP-235 as a potent inhibitor of SARS-CoV-2 and show that it is effective against a range of variants and other coronaviruses and that it suppresses virus replication, reduces lung damage, and prevents transmission in small animal models.

Spatiotemporal waves appear during collective cell migration and are affected by mechanical forces and biochemical signalling. Here the authors develop a biophysical model that can quantitatively account for complex mechanochemical patterns, and predict how they can be used for optimal collective migration.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

Virus reassortment drives genetic diversity and evolution and is governed by intra-host dynamics that are less well understood. Here, the authors characterise the within-host dynamics of influenza A virus reassortment in swine, ferrets and guinea pigs, considering their spatial distribution.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

Synthetic cell adhesion molecules yield customized cell–cell interactions with adhesion properties that are similar to native interactions, and offer abilities for cell and tissue engineering and for systematically studying multicellular organization.

Phenazine biosynthesis-like domain-containing protein (PBLD) and cedrelone play roles in tumor suppression. Here, authors suggest that PBLD and Cedrelone inhibit viral replication via activating the NF-κB-mediated IFN-I signaling response in cells and mice.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.

In this work, a nanobody based intermolecular strain sensor was used to follow the mechanical strain in the nuclear lamina. The results indicate that mechanical state of the nuclear lamina is not only affected by the cell contractility, but also chromatin packing.

A nanoparticle influenza vaccine candidate is shown to induce broad cross-reactive antibody responses in animal models.

A cell-cycle checkpoint triggers the extrusion of both nematode and mammalian cells experiencing replication stress.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

Adopting a round cell morphology before mitosis is crucial. Here, the authors show that in mitosis integrins binding to ligands do not engage the actomyosin cortex, which curbs cell-extracellular matrix adhesion, though β1 integrins are rewired to synergize with cadherins in mitotic cell-cell adhesion.

Chimeric particles are formed when influenza A virus and respiratory syncytial virus coinfect lung cells in vitro.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.

In chickens, influenza A virus relies on host protein ANP32A. Here the authors use CRISPR/Cas9 to generate homozygous gene edited chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction.

The role of T cells in modulating the course of influenza infection in humans is not clear. Wilkinson et al. now report that, in the absence of strain-specific humoral immunity, preexisting cytotoxic CD4⁺ T cells limit the severity and duration of symptoms in humans challenged with influenza virus and suggest these CD4⁺ T cell responses might be harnessed in vaccine development.

Rho kinases regulate the actin cytoskeleton by controlling stress fibre formation. Truebestein et al.show that the length of its coiled-coil determines ROCK2 function, and propose that the coiled coil acts as a spacer, targeting kinase activity to a discrete distance from the membrane.

The interferon-inducible RNA-binding protein N4BP1 binds to and degrades HIV-1 mRNAs, thus inhibiting viral degradation and promoting viral latency. However, metacaspase-mediated degradation of N4BP1 following activation of CD4⁺ T cells facilitates HIV-1 latency reversal.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Productive influenza infection can be improved by cooperation and this varies between viral strains and hosts. By quantifying the rates of reassortment and virus production using several methods, including single-cell sequencing, the authors find that isolates of the avian H9N2 influenza subtype are dependent on infections with a second virus, but only in mammalian cells and not in avian cells. These findings are supported by in vivo experiments in guinea pigs and quail. The authors find indications that this type of cooperation between influenza A viruses depends on the RNA polymerase subunit PA.

When a wound heals, different types of branched and bundled actin structure form, each designed to perform a specific function. Experiments and theory now suggest that the actin architecture depends on the stiffness of the cell’s surroundings.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Reversible palmitoylation controls the localization and signaling of Ras. Development of a potent and specific small molecule inhibitor of the thioesterase APT1 reveals that this enzyme depalmitoylates Ras in cells. Inhibition of APT1 led to redistribution and altered activity of HRas, NRas and an oncogenic mutant Ras.

The sexually transmitted human parasite Trichomonas vaginalis belongs to a clade of host-switching trichomonads that parasitize mammals, birds, livestock, and pets. Here the authors describe a chromosome-scale genome for T. vaginalis and assemblies of other bird and mammal-infecting species, identifying gene functions implicated in the spillover of trichomonads from birds to humans.

About a third of the sediment delivery of the Mekong River is shown to be associated with rainfall generated by tropical cyclones, suggesting that future delta stability will be strongly moderated by changes to tropical cyclone intensity, frequency and track.

High mutation rates in the influenza A virus facilitate the generation of viral escape mutants, rendering vaccines and drugs potentially ineffective, but targeting host cell determinants could prevent viral escape. Here, 287 human host cell genes influencing influenza A virus replication are found using a genome-wide RNA interference screen. An independent assay is then used to investigate overlap between genes necessary for different viral strains.

How the cell goes about its routine mechanical business of stretching, contracting, and remodelling has implications for understanding excessive airway narrowing in asthma, cell invasion in cancer and vessel constriction in vascular disease. Surprisingly, the cell is an intermediate form of matter, neither solid nor fluid but retaining features of both - that responds to stretch by fluidizing, much as do common pastes, foams, clays, and colloids.

An atomic force microscope and confocal microscope set-up that allows nanomechanical mapping of virus binding under cell culture conditions shows that the first binding steps of a virus to a cell surface receptor are specific and weak, but affinity increases as more bonds are formed between the virus and cell surface receptors.

New influenza virus vaccines tested in humans elicit broadly cross-reactive antibodies that bind the stalk of the viral hemagglutinin protein and may serve as templates to design a universal influenza vaccine.

HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.