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Nanozymes are nanomaterials exhibiting intrinsic enzyme-like characteristics that have increasingly attracted attention, owing to their high catalytic activity, low cost and high stability. This combination of properties has enabled a broad spectrum of applications, ranging from biological detection assays to disease diagnosis and biomedicine development. Since the intrinsic peroxidase activity of Fe3O4 nanoparticles (NPs) was first reported in 2007, >40 types of nanozymes have been reported that possess peroxidase-, oxidase-, haloperoxidase- or superoxide dismutase–like catalytic activities. Given the complex interdependence of the physicochemical properties and catalytic characteristics of nanozymes, it is important to establish a standard by which the catalytic activities and kinetics of various nanozymes can be quantitatively compared and that will benefit the development of nanozyme-based detection and diagnostic technologies. Here, we first present a protocol for measuring and defining the catalytic activity units and kinetics for peroxidase nanozymes, the most widely used type of nanozyme. In addition, we describe the detailed experimental procedures for a typical nanozyme strip–based biological detection test and demonstrate that nanozyme-based detection is repeatable and reliable when guided by the presented nanozyme catalytic standard. The catalytic activity and kinetics assays for a nanozyme can be performed within 4 h.

Coronavirus disease 2019 (COVID-19) was first identified in late 2019 in Wuhan, Hubei Province, China and spread globally in months, sparking worldwide concern. However, it is unclear whether super-spreading events occurred during the early outbreak phase, as has been observed for other emerging viruses. Here, we analyse 208 publicly available SARS-CoV-2 genome sequences collected during the early outbreak phase. We combine phylogenetic analysis with Bayesian inference under an epidemiological model to trace person-to-person transmission. The dispersion parameter of the offspring distribution in the inferred transmission chain was estimated to be 0.23 (95% CI: 0.13–0.38), indicating there are individuals who directly infected a disproportionately large number of people. Our results showed that super-spreading events played an important role in the early stage of the COVID-19 outbreak. Although SARS-CoV-2 has spread rapidly, the contribution of super-spreading events to transmission is unclear. Here, the authors show that the number of secondary infections arising from an individual infection in the early phase of the outbreak was highly skewed, indicating that super-spreading events occurred.

On March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identified. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian influenza viruses with ecological information and did phylogenetic and coalescent analyses to extrapolate the potential origins of the virus and possible routes of reassortment events. We downloaded H7N9 virus genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database and public sequences used from the Influenza Virus Resource. We constructed phylogenetic trees and did 1000 bootstrap replicates for each tree. Two rounds of phylogenetic analyses were done. We used at least 100 closely related sequences for each gene to infer the overall topology, removed suspicious sequences from the trees, and focused on the closest clades to the novel H7N9 viruses. We compared our tree topologies with those from a bayesian evolutionary analysis by sampling trees (BEAST) analysis. We used the bayesian Markov chain Monte Carlo method to jointly estimate phylogenies, divergence times, and other evolutionary parameters for all eight gene fragments. We used sequence alignment and homology-modelling methods to study specific mutations regarding phenotypes, specifically addressing the human receptor binding properties. The novel avian influenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian influenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway. The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza viruses, which were isolated from chickens. Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus. Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades. The novel avian influenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched in the future. China Ministry of Science and Technology Project 973, National Natural Science Foundation of China, China Health and Family Planning Commission, Chinese Academy of Sciences.

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus. Many domestic animals, among them dogs, have been infected with SARS-CoV-2 during the COVID-19 pandemic. Here, the authors present the crystal structure of the SARS-CoV-2 spike protein receptor binding domain (RBD) bound to its receptor, dog angiotensin-converting enzyme 2 (dACE2), and show that the RBD N501Y mutation increases the infectivity and host range of SARS-CoV-2, which highlights the need to monitor emerging SARS-CoV-2 mutations in domestic animals.

Nipah virus (NiV) is a non-segmented, negative-strand (NNS) RNA virus, belonging to Paramyxoviridae. The RNA polymerase complex, composed of large (L) protein and tetrameric phosphoprotein (P), is responsible for genome transcription and replication by catalyzing NTP polymerization, mRNA capping and cap methylation. Here, we determine the cryo-electron microscopy (cryo-EM) structure of fully bioactive NiV L-P polymerase complex at a resolution of 3.19 Å. The L-P complex displays a conserved architecture like other NNS RNA virus polymerases and L interacts with the oligomerization domain and the extreme C-terminus region of P tetramer. Moreover, we elucidate that NiV is naturally resistant to the allosteric L-targeting inhibitor GHP-88309 due to the conformational change in the drug binding site. We also find that the non-nucleotide drug suramin can inhibit the NiV L-P polymerase activity at both the enzymatic and cellular levels. Our findings have greatly enhanced the molecular understanding of NiV genome replication and transcription and provided the rationale for broad-spectrum polymerase-targeted drug design. The Nipah virus (NiV) polymerase complex is an ideal target for drug development. Here, the authors determine the cryo-EM structures of NiV L-P polymerase complexes and reveal how NiV is resistant to the allosteric L-targeting inhibitor GHP-88309. Furthermore, the authors demonstrate that suramin could inhibit NiV L-P complex at both enzymatic and cellular levels.

Background Antibiotic-resistant pathogens pose high risks to human and animal health worldwide. In recent years, the role of gut microbiota as a reservoir of antibiotic resistance genes (ARGs) in humans and animals has been increasingly investigated. However, the structure and function of the gut bacterial community, as well as the ARGs they carry in migratory birds remain unknown. Results Here, we collected samples from migratory bird species and their associated environments and characterized their gut microbiomes and resistomes using shotgun metagenomic sequencing. We found that migratory birds vary greatly in gut bacterial composition but are similar in their microbiome metabolism and function. Birds from the same environment tend to harbor similar bacterial communities. In total, 1030 different ARGs (202 resistance types) conferring resistance to tetracycline, aminoglycoside, β-lactam, sulphonamide, chloramphenicol, macrolide-lincosamide-streptogramin (MLS), and quinolone are identified. Procrustes analysis indicated that microbial community structure is not correlated with the resistome in migratory birds. Moreover, metagenomic assembly-based host tracking revealed that most of the ARG-carrying contigs originate from Proteobacteria . Co-occurrence patterns revealed by network analysis showed that emrD , emrY , ANT(6)-Ia , and tetO , the hubs of ARG type network, are indicators of other co-occurring ARG types. Compared with the microbiomes and resistomes in the environment, migratory birds harbor a lower phylogenetic diversity but have more antibiotic resistance proteins. Interestingly, we found that the mcr-1 resistance gene is widespread among different birds, accounting for 50% of the total samples. Meanwhile, a large number of novel β-lactamase genes are also reconstructed from bird metagenomic assemblies based on fARGene software. Conclusions Our study provides a comprehensive overview of the diversity and abundance of ARGs in migratory birds and highlights the possible role of migratory birds as ARG disseminators into the environment. 9vRT3BmK5LZQjoS1YmKYZo Video abstract.

Circular RNAs (circRNAs) are involved in various biological roles, including viral infection and antiviral immune responses. To identify influenza A virus (IAV) infection-related circRNAs, we compared the circRNA profiles of A549 cells upon IAV infection. We found that circVAMP3 is substantially upregulated after IAV infection or interferon (IFN) stimulation. Furthermore, IAV and IFN-β induced the expression of QKI-5, which promoted the biogenesis of circVAMP3 . Overexpression of circVAMP3 inhibited IAV replication, while circVAMP3 knockdown promoted viral replication, suggesting that circVAMP3 restricts IAV replication. We verified the effect of circVAMP3 on viral infection in mice and found that circVAMP3 restricted IAV replication and pathogenesis in vivo . We also found that circVAMP3 functions as a decoy to the viral proteins nucleoprotein (NP) and nonstructural protein 1 (NS1). Mechanistically, circVAMP3 interfered with viral ribonucleoprotein complex activity by reducing the interaction of NP with polymerase basic 1, polymerase basic 2, or vRNA and restored the activation of IFN-β by alleviating the inhibitory effect of NS1 to RIG-I or TRIM25. Our study provides new insights into the roles of circRNAs, both in directly inhibiting virus replication and in restoring innate immunity against IAV infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, emerged in December 2019. Its origins remain uncertain. It has been reported that a number of the early human cases of coronavirus disease 2019 had a history of contact with the Huanan Seafood Market. Here we present the results of surveillance for SARS-CoV-2 within the market. From 1 January 2020, after closure of the market, 923 samples were collected from the environment. From 18 January, 457 samples were collected from 18 species of animal, comprising unsold contents of refrigerators and freezers, swabs from stray animals and the contents of a fish tank. Using quantitative real-time polymerase chain reaction (RT-qPCR) and high-throughput sequencing (Bowtie2 analysis), SARS-CoV-2 was detected in 74 (70 RT-qPCR and 4 Bowtie2) environmental samples, but none of the animal samples. Three live viruses were successfully isolated. The viruses from the market shared a nucleotide identity of 99.99% to 100% with the human isolate HCoV-19/Wuhan/IVDC-HB-01/2019. SARS-CoV-2 lineage A (8782T and 28144C) was found in an environmental sample. RNA-sequencing analysis of SARS-CoV-2-positive and SARS-CoV-2-negative environmental samples showed an abundance of different vertebrate genera at the market. In summary, this study provides information about the distribution and prevalence of SARS-CoV-2 in the Huanan Seafood Market during the early stages of the outbreak of coronavirus disease 2019. A study presents the results of surveillance for SARS-CoV-2 in animal and environmental samples from a market linked to early human cases of coronavirus disease 2019.

We have surveyed avian influenza virus (AIV) genomes from live poultry markets within China since 2014. Here we present a total of 16,091 samples that were collected from May 2016 to February 2019 in 23 provinces and municipalities in China. We identify 2048 AIV-positive samples and perform next generation sequencing. AIV-positive rates (12.73%) from samples had decreased substantially since 2016, compared to that during 2014–2016 (26.90%). Additionally, H9N2 has replaced H5N6 and H7N9 as the dominant AIV subtype in both chickens and ducks. Notably, novel reassortants and variants continually emerged and disseminated in avian populations, including H7N3, H9N9, H9N6 and H5N6 variants. Importantly, almost all of the H9 AIVs and many H7N9 and H6N2 strains prefer human-type receptors, posing an increased risk for human infections. In summary, our nation-wide surveillance highlights substantial changes in the circulation of AIVs since 2016, which greatly impacts the prevention and control of AIVs in China and worldwide. In this study, the authors present a genomic surveillance of avian influenza genomes sampled from live poultry markets in China. They report that a number of variants have emerged since 2016 that pose an increased risk to humans. They highlight the importance of continuous genome surveillance of circulating influenza strains.

RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase, functioned as a critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS. In addition, CypA and TRIM25 competitively interacted with MAVS, thereby inhibiting TRIM25-induced K48-linked ubiquitination of MAVS. Taken together, our findings reveal an essential role of CypA in boosting RIG-I-mediated antiviral immune responses by controlling the ubiquitination of RIG-I and MAVS. In mammals, an enzyme called Cyclophilin A (CypA) is found in almost all tissues and plays important roles in many biological processes including the production of proteins and inflammation. Recent work suggests that it also plays a role in fighting virus infections. CypA can interact directly with a protein from viruses to inhibit the virus from multiplying. Several lines of evidence indicate that CypA can also regulate virus replication by stimulating the production of molecules called type I interferons, but it is not clear how this could work. A receptor protein called RIG-I can detect the presence of a virus and interact with another protein called MAVS to stimulate immune responses, leading to the production of type I interferons. Liu, Li et al. used human cells and mice to investigate how CypA affects this process. The experiments show that the levels of CypA in cells increase during virus infection. Cells that lack CypA produce fewer type I interferon molecules, which gives the virus more of a chance to multiply. Further experiments show that CypA alters the ubiquitin-mediated protein modification of RIG-I and MAVS. The findings of Liu, Li et al. identify a new way in which CypA boosts immune responses during virus infections. A future challenge is to develop new drugs that regulate the protein modification of RIG-I and MAVS, which may help to treat virus infections.