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Influenza virus ribonucleoprotein complexes (RNPs) are essential for replication and transcription. Here, authors solve the cryo-EM structure of influenza mini-vRNP to reveal detailed FluPol–NP–RNA coupling and suggest a conformational shift in RNPs during the viral life cycle.

Crystal structures of cyanobacterial protochlorophyllide oxidoreductases reveal the basis of the photocatalytic activities of this enzyme, through the role of its active site in enabling the light-driven reduction of protochlorophyllide.

SARS-CoV-2 virus replication and transcription is mediated by the replication and transcription complex (RTC) that is composed of 16 non-structural proteins (nsp). Here, the authors present the cryo-EM structure of a SARS-CoV-2 mini RTC consisting of the viral RNA-dependent RNA polymerase with a template-primer RNA, the RdRp cofactors nsp7 and nsp8 and two nsp13 helicase molecules, and they propose a model for helicase-polymerase coupling during SARS-CoV-2 RTC assembly.

Multiple adeno-associated viruses (AAV) use the same receptor (AAVR), but the binding mode is not clear. Here, the authors determine the structures of the AAV1-AAVR and AAV5-AAVR complexes, identify residues necessary for virus entry and compare the receptor interfaces of different AAV capsids.

This study investigates the HCoV-HKU1 RBD-TMPRSS2 interaction, identifying two antibody types: one that blocks RBD-TMPRSS2 binding, while the other inhibits TMPRSS2, showing broad anti-coronavirus potential.

PCDH10 is a general receptor for WEEV. This work reveals the structural basis of WEEV recognition by PCDH10 and provides a plausible explanation for the receptor shift occurring through WEEV strains.

The MmpL5/MmpS5 efflux system is crucial for drug extrusion and siderophore export in M. tuberculosis. Here, the authors report its high-resolution cryo-EM structures, revealing a unique trimeric assembly and a flexible extracellular stalk.

The exact role of the degenerate nucleotide-binding site in a heterodimeric ABC transporter is unclear. Here, authors identify a mycobacterial isoniazid efflux pump, capture its asymmetric intermediate states and reveal mechanism of this transporter mediated by the degenerate site.

Structural and biochemical studies of the monkeypox virus core protease show that it exists as an active homodimer and indicate that the substrate-binding sites of core proteases are a promising target for antiviral drugs.

African swine fever virus (ASFV) is a contagious DNA virus causing lethal disease in swine. This study reveals structures of ASFV RNA polymerase bound to protein M1249L, showing its vital roles in regulating early transcription and packaging.

The structure of enterovirus 71 in complex with its receptor SCARB2 provides insights into the mechanism of viral uncoating within the endo/lysosome compartment and identifies few conserved key residues within the binding footprint that might facilitate the design of receptor mimic therapeutics.

A crystal structure of SARS-CoV-2 with inhibitor carmofur reveals the mechanism of action of this compound and opens the way to develop more potent drugs.

Here the authors determine multiple conformational structures of T4 and T6 bacteriophage topoisomerase IIs when breaking G-segment DNA, identifying a unique insertion in the TOPRIM domain of the T4 topoisomerase II, and a difference in the catalytic centers of the dimers.

African swine fever virus is the sole mammalian-infecting virus encoding a type II topoisomerases (pP1192R). The authors present pP1192R structures in different states, illustrating the enzymatic mechanisms of viral type II topoisomerases.

Cryogenic electron microscopy structures of Mycobacterium tuberculosis ATP synthase and human ATP synthase bound to the anti-tuberculosis drug bedaquiline or its analogue TBAJ-587 shed light on drug binding and could lead to new treatments for tuberculosis.

Here, four cryo-EM structures of Mtb OppABCD reveal an assembly of a cluster C substrate-binding protein and its translocator, as well as the [4Fe–4S] cluster-regulated transport mechanism of oligopeptide permeases found in bacteria.

Cryogenic electron microscopy analysis of the Mycobacterium tuberculosis membrane-bound phosphoribosyltransferase Rv3806c provides mechanistic insight into cell wall precursor synthesis.

Most recent SARS-CoV-2 variants showed exceptional immune evasion properties. Here, the authors identify a highly conserved epitope within the RBD targeted by a broad spectrum neutralizing antibody BA7535 that shows therapeutic antiviral potency in mouse studies.

The study by Fu and colleagues presents a ferritin-adaptor platform for vaccine development, featuring a rabies virus vaccine candidate that enhances antigen stability and provides potent, durable protection after a single-dose administration.

The structure of Aichi virus — a poorly characterized picornavirus that causes severe gastroenteritis in children — shows intermediate features between those of enteroviruses and cardioviruses, and provides clues into its cellular receptor.

TMPRSS2 and CTSL/CTSB, host proteases that facilitate SARS-CoV-2 entry, are promising drug targets. Here the authors simultaneously inhibit these host proteases and see synergistic antiviral effects, offering a broad-spectrum intervention against SARS-CoV-2 variants.

A biochemical and structural analysis demonstrates that alterations at the substrate-binding pocket of the main protease of SARS-CoV-2 can allow the virus to develop resistance to nirmatrelvir in two distinct ways.

Neurons in the dorsal motor nucleus of vagus are involved in the absorption of fat in the intestine, and the natural compound puerarin shows utility in modulating this brain–gut axis to reduce fat absorption.

Newcastle disease virus (NDV) belongs to Paramyxoviridae and encodes a large protein (L) and phosphoprotein (P) for viral RNA synthesis. Here the authors present cryo-EM structures of the L-P complex, and propose a model of how RNA initiation/elongation alternates during viral RNA synthesis.

Hydroxyl-carboxylic acid receptor 2 (HCA2) functions as a high-affinity receptor for nicotinic acid (vitamin B3). Here, authors report the cryo-EM structure of the HCA2-G_i complex with the agonist MK-6892 and inactive state crystal structures of mutation stabilized HCA2, to describe the mechanism of HCA2 signaling.

Here, using structural and biochemical methods, the authors reveal the existence of an intermediate state of the influenza polymerase, which allows it to toggle between the transcribing and replicative states.

Antibodies against SARS-CoV-2 S protein can provide a treatment strategy for COVID-19. Here, Guo et al. provide the crystal structure of a SARS-CoV2 neutralizing antibody isolated from a convalescent patient and highlight the therapeutic efficacy in a rhesus monkey model of an engineered version with optimized pharmacokinetic and safety profile.

Ebselen is an organoselenium drug that inhibits the SARS-CoV-2 main protease (M^pro). Here, the authors co-crystallised M^pro with ebselen and an ebselen derivative and observed an enzyme bound organoselenium covalent adduct in the crystal structures, which was also confirmed by mass spectrometry analysis.

Cytochromes bd oxidase (Cyt-bd) catalyzes the reduction of oxygen to water and is the terminal oxidase in the respiratory chain of prokaryotes. Here, the authors present the 2.8 Å cryo-EM structure of Mycobacterium smegmatis Cyt-bd and identify two potential oxygen access channels in the structure, which is of interest for the development of novel antituberculosis drugs.

Junin virus (JUNV) causes Argentine hemorrhagic fever and encodes the large protein (L) of the RNA dependent RNA polymerase (RdRp) and its regulator, the matrix zinc-binding protein (Z). Here, the authors present the 3.54 Å cryo-EM structure of the complex of JUNV L with Z, and they propose a model of how JUNV L is regulated by Z during the viral life cycle and RNA synthesis.

Mycobacterium tuberculosis suppresses the production of inflammatory cytokines by host cells through the host-mediated ubiquitination of a mycobacterial protein, enhancing the interaction of a host signalling inhibitor with another signalling molecule.

So far no vaccine or antiviral therapy is available for Echovirus 30 (E30) that causes aseptic meningitis. Here, the authors generate and characterise two E30-specific monoclonal antibodies that block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn, and determine the cryo-EM structures of E30 with the bound neutralizing antibodies.

Tuberculosis drugs induce the expression of IniA, but so far little has been known about its structure and function. Here the authors present the apo and GTP bound crystal structures of Mycobacterium smegmatis IniA, which folds as a bacterial dynamin-like protein and show that IniA mediates membrane fission in vitro.

Structures of the acetohydroxyacid synthase complexes of Saccharomyces cerevisiae and Arabidopsis thaliana provide insights into the biosynthesis of and feedback inhibition by branched-chain amino acids.

A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.

Here, the authors provide the structure of mature Coxsackie Virus A10 alone and in complex with its receptor KREMEN1, and of A-particles. This shows how the receptor spans the viral canyon and suggests that receptor binding triggers pocket factor release and conformational changes resulting in expanded particles.

Crystal structures of PAFR in complex with the antagonist SR 27417 and the inverse agonist ABT-491, together with accompanying experiments, provide insight into recognition of PAF and reveal an unusual ligand-dependent conformation of helical bundle.

The authors present the full-length structure of the polymerase (L protein) from the severe fever with thrombocytopenia syndrome virus (SFTSV)—a segmented, negative-stranded RNA virus. The structure reveals important details with implications for the understanding of viral transcription and replication, and provides information on the organization of the polymerase core domain, entrance and exit tunnels, as well as the cap-binding and endonuclease domains.

Echovirus 30 (E30) belongs to the Enterovirus-B group and causes aseptic meningitis in humans. Here, the authors present the cryo-EM structures of the E30 E-particle, A-particle and the mature virion, as well as structures of E30 in complex with its receptor FcRn and CD55, and furthermore they describe a structure-based algorithm that allows the prediction of EV receptor usage.

The structure of adeno-associated virus (AAV) type 2 in complex with its receptor, AAVR, provides new insights on the molecular mechanism of AAV entry into host cells and will serve to optimize the design of AAV vectors for gene therapy.

Diheme-containing succinate:menaquinone oxidoreductases (Sdh) are members of the complex II superfamily. Here, the authors present the 2.8 Å cryo-EM structure of Mycobacterium smegmatis Sdh2, which reveals membrane-anchored SdhF as a component of the complex and they discuss the electron/proton transfer pathway in the Sdh2 trimer.

Progression of chronic kidney disease may lead to kidney failure and cardiovascular, metabolic and bone disease complications. Here, the authors conduct a large-scale proteomic study in patients with chronic kidney disease, identify numerous proteins that predict kidney failure, some of which are likely causal mediators and hence potential therapeutic targets.

In this study, the authors isolated and characterized neutralizing antibodies from vaccinated individuals with SARS-CoV-2 BA.1 breakthrough infection and show that elite antibodies derived from specific germlines provide potent pan-variant neutralization capacity and in vivo protection.

The Ljungan virus is a picornavirus that lacks the internal coat protein VP4, and the packaging of its RNA genome is poorly understood. Here, the authors use cryo-electron microscopy to visualize this virus and suggest that it uses a different mechanism to other viruses for encapsidation of its genome.

The detailed mechanism of how non-enveloped viruses initiate infection remains obscure. Ren et al. present the atomic structure of an uncoating intermediate for the human picornavirus CAV16, revealing a major capsid protein partly extruded from the capsid and suggesting a model for RNA release.

Foot-and-mouth disease virus binds αvβ6 integrin, via a conserved RGD motif in the flexible, exposed GH loop of capsid protein VP1, for cell entry. Here Kotechaet al.visualize this interaction with the VP1 GH loop extending away from the viral surface, engaging αvβ6 in an open, active state.