The newly emerged BA.2.75 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant contains 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here, ...we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in S. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2 but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, reduces BA.2.75 neutralization resistance. The impact of these mutations is consistent with their locations in common neutralizing antibody epitopes. Further, BA.2.75 shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling reveals enhanced receptor contacts introduced by N460K, suggesting a mechanism of potentiated receptor utilization and syncytia formation.
•BA.2.75 shows enhanced neutralization resistance and fusion over BA.2 but not BA.4/5•G446S, and to a lesser extent N460K, determines enhanced neutralization resistance•N460K drives enhanced spike processing and cell-cell fusion of BA.2.75•N460K potentiates ACE2 interactions likely by forming a salt bridge and hydrogen bond
Newly emerged Omicron subvariants reignite concerns over escape from existing immunity. Qu and colleagues compare the immunity resistance and fusogenicity of BA.2.75 with prior variants. BA.2.75 exhibits stronger neutralization resistance than BA.2 but weaker than BA.4/5, as well as enhanced fusogenicity, which are largely driven by G446S and N460K, respectively.
The Maillard reaction is of great significance in food, herb medicines, and life processes. It is usually occurring during the process of food and herb medicines processing and storage. The formed ...Maillard reaction productions (MRPs) in food and herb medicines not only generate a large number of efficacy components but also generate a small amount of harmful substance that cannot be ignored. Some of the MRPs, especially the advanced glycation end products (AGEs) are concerning humans, based on the possibility to induce cancer and mutations in laboratory animals. Numerous studies have been reported on the formation, analysis, and control of the potentially harmful MRPs (PHMRPs). Therefore, the investigation into the formation, analysis, and control of PHMRPs in food and herb medicines is very important for improving the quality and safety of food and herb medicines. This article provides a brief review of the formation, analysis (major content), and control of PHMRPs in food and herb medicines, which will provide a base and reference for safe processing and storage of food and herb medicines. Practical Applications. The formed Maillard reaction productions in food and herb medicines not only generate a large number of functional components but also generate a small amount of harmful substance that cannot be ignored. This contribution provides a brief review on the formation (including the correlative studies between MRs and the PHMRPs, mechanisms, and the main pathways); analysis (major content, pretreatment for analysis, qualitative and quantitative analysis, and structural identification analysis); and control (strategies and mechanisms) of PHMRPs in food and herb medicines, which will provide a solid theoretical foundation and a valuable reference for safe processing and storage for food and herb medicines.
Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, ...BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose-vaccinated and bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had relatively high fusogenicity and infectivity in CaLu-3 cells but low fusion and infectivity in 293T-ACE2 cells compared to some XBB variants, suggesting a potentially different conformational stability of BA.2.86 spike. Overall, our study underscores the importance of SARS-CoV-2 variant surveillance and the need for updated COVID-19 vaccines.
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•BA.2.86 is less immune evasive compared to FLip and other XBB variants•BA.2.86 is antigenically more similar to BA.2 and BA.4/5 than XBB variants•MAb S309 is unable to neutralize BA.2.86 possibly contributed by a D339H mutation•The fusion and infectivity of BA.2.86 is higher than XBB variants in CaLu-3 cells
The SARS-CoV-2 BA.2.86 variant is less resistant to neutralization by bivalent vaccine-induced antibodies compared to FLip and other XBB variants but more resistant to mAb S309. BA.2.86 shows higher fusogenicity and infectivity in CaLu-3 cells compared to that in 293T-ACE2 cells.
Abstract
Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells ...(http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs’ functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution.
A small study assessed the neutralization of pseudoviruses composed of the recombinant deltacron and omicron BA.3 variants. BA.3 did not show broad cross-resistance, but deltacron was largely ...resistant to immune response elicited either by three doses of mRNA vaccines or by previous infection.
Phytochemical investigation on the Panax notoginseng fruits (PNF) led to the isolation of twelve compounds, including nine triterpenoid saponins (1–9) and three flavonoids (10–12). The structures of ...these isolates were identified on the basis of spectroscopic analysis, as well as comparisons with the data available in the literature. All compounds were firstly isolated from PNF, among them, compound 1 was firstly obtained as a natural product, compound 2 was reported for the first time in family Araliaceae, moreover, the complete 1H- and 13C- NMR spectra of this isolate was reported for the first time. Furthermore, the chemotaxonomic significance of these compounds was discussed.
•Twelve compounds were firstly isolated from the Panax notoginseng fruits.•Compound 1 was firstly obtained as a natural product.•Compound 2 was reported for the first time in family Araliaceae.•These compounds enrich the chemical diversity of the family Araliaceae.
The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit generally reduced ...fusogenicity and increased endosomal entry pathway utilization compared to the ancestral D614G variant, the underlying mechanisms of which remain elusive. Here, we show that the C-terminal S1 mutations of the BA.1.1 subvariant, H655Y and T547K, critically govern the low fusogenicity of Omicron. Notably, H655Y also dictates the enhanced endosome entry pathway utilization. Mechanistically, T547K and H655Y likely stabilize the spike trimer conformation as suggested by increased molecular interactions in structural modeling and enhanced S1 shedding of their reversion mutants K547T and Y655H in viral producer cells. Importantly, the H655Y mutation also determines the low fusogenicity and enhanced dependence on the endosomal entry pathway of other Omicron subvariants, including BA.2, BA.2.12.1, BA.4/5, and BA.2.75. Together, these results uncover mechanisms governing Omicron subvariant entry and provide insights into altered Omicron tissue tropism and pathogenesis.
Omicron has been shown to predominantly use the endosomal entry pathway, resulting in reduced lung tropism and reduced disease severity; however, the underlying mechanism is not fully understood. In addition, whether the most recent Omicron subvariants, including BA.5 and BA.2.75, use the same pathway as their ancestor for entry is currently not known. In this study, we show that T547K and H655Y mutations in the C terminus of the S1 subunit critically determine the enhanced dependence on the endosomal entry pathway as well as the reduced cell-cell fusion activity of Omicron BA.1, BA.1.1, and other subvariants. Further experiments and molecular modeling suggest that H655Y and K547T stabilize the spike trimer conformation, likely contributing to the decreased fusogenicity and endosomal entry. Our work uncovers novel mechanisms underlying the distinct entry pathway of Omicron subvariants and advances our understanding of their biological characteristics.
The sensitivity of SARS-CoV-2 variants of concern (VOCs) to neutralizing antibodies has largely been studied in the context of key receptor binding domain (RBD) mutations, including E484K and N501Y. ...Little is known about the epistatic effects of combined SARS-CoV-2 spike mutations. We now investigate the neutralization sensitivity of variants containing the non-RBD mutation Q677H, including B.1.525 (Nigerian isolate) and Bluebird (U.S. isolate) variants. The effect on neutralization of Q677H was determined in the context of the RBD mutations and in the background of major VOCs, including B.1.1.7 (United Kingdom, Alpha), B.1.351 (South Africa, Beta), and P1-501Y-V3 (Brazil, Gamma). We demonstrate that the Q677H mutation increases viral infectivity and syncytium formation, as well as enhancing resistance to neutralization for VOCs, including B.1.1.7 and P1-501Y-V3. Our work highlights the importance of epistatic interactions between SARS-CoV-2 spike mutations and the continued need to monitor Q677H-bearing VOCs.
SARS-CoV-2, the causative agent of COVID-19, is rapidly evolving to be more transmissible and to evade acquired immunity. To date, most investigations of SARS-CoV-2 variants have focused on RBD mutations. However, the impact of non-RBD mutations and their synergy with studied RBD mutations are poorly understood. Here, we examine the role of the non-RBD Q677H mutation arising in many SARS-CoV-2 lineages, including VOCs. We demonstrate that the Q677H mutation enhances viral infectivity and confers neutralizing antibody resistance, particularly in the background of other SARS-CoV-2 VOCs.
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the efficacy of vaccination efforts against coronavirus disease 2019 (COVID-19). The Omicron XBB ...lineage of SARS-CoV-2 has presented dramatic evasion of neutralizing antibodies stimulated by mRNA vaccination and COVID-19 convalescence. XBB.1.16, characterized by two mutations relative to the dominating variant XBB.1.5, i.e., E180V and K478R, has been on the rise globally. In this study, we compare the immune escape of XBB.1.16 with XBB.1.5, alongside ancestral variants D614G, BA.2, and BA.4/5. We demonstrate that XBB.1.16 is strongly immune evasive, with extent comparable to XBB.1.5 in bivalent-vaccinated healthcare worker sera, 3-dose-vaccinated healthcare worker sera, and BA.4/5-wave convalescent sera. Interestingly, the XBB.1.16 spike is less fusogenic than that of XBB.1.5, and this phenotype requires both E180V and K478R mutations to manifest. Overall, our findings emphasize the importance of the continued surveillance of variants and the need for updated mRNA vaccine formulations.
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•XBB.1.16 exhibits high extents of immune escape comparable to XBB.1.5•XBB.1.16 escapes neutralizing antibodies in bivalent- and 3-dose-vaccinated sera•XBB.1.16 spike is less fusogenic than XBB.1.5 due to the E180V and K478R mutations•Higher infectivity of XBB.1.16 in 293T-ACE2 cells is driven by the K478R mutation
SARS-CoV-2 continues to exhibit increasing immune escape. Here, Faraone et al. demonstrate that XBB.1.16 escapes antibodies in bivalent-vaccinated, 3-dose-vaccinated, and BA.4/5-wave convalescent sera to a similar extent compared with XBB.1.5. They also show that the XBB.1.16 spike is less fusogenic than XBB.1.5 but exhibits enhanced infectivity.
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