COVID -19: On the threshold of the fifth year. The situation in Spain DOI Creative Commons
Fernando Rodríguez‐Artalejo, Julián Ruiz‐Galiana, Rafael Cantón

et al.

Revista Española de Quimioterapia, Journal Year: 2023, Volume and Issue: 37(1), P. 17 - 28

Published: Nov. 27, 2023

Despite having emerged from pandemic status, the incidence of COVID-19 episodes has recently increased in Spain, including pediatric cases and admissions to Intensive Care Units. Several recombinant variants are circulating among us, particularly XBB arising two Omicron BA.2 sublineages with mutations genes encoding spicule proteins that could increase binding ACE2 receptor be more prone immune escape. Faced these, 3 pharmaceutical companies have developed vaccines adapted XBB.1.5 sublineage already available for administration our setting risks should not different those previous mRNA clearly favorable benefit/risk ratios. They applied patients potential poor evolution collectives a particular relationship proximity them. Their application understood only perspective individual convenience but also collective responsibility. The most convenient seems simultaneous immunization influenza environment. In therapeutic aspect, there is little expect right now antisera, known antiviral drugs still indicated, although their efficacy will reevaluated due impact on populations mostly immunized better prognosis than past. opinion, it necessary continue make reasonable timely use masks other non-pharmacological means protection.

Language: Английский

Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion DOI Creative Commons

Song Xue,

Yuru Han, Fan Wu

et al.

Protein & Cell, Journal Year: 2024, Volume and Issue: 15(6), P. 403 - 418

Published: March 4, 2024

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within receptor binding domain (RBD) spike (S) protein, lead to functional alteration both engagement monoclonal antibody (mAb) recognition. Here, we review data RBD point mutations possessed by major discuss their individual effects on ACE2 affinity immune evasion. Many single amino acid substitutions epitopes crucial for evasion capacity may conversely weaken affinity. However, this weakened effect could be largely compensated specific epistatic such as N501Y, thus maintaining overall protein all variants. The predominant direction evolution lies neither promoting nor evading mAb neutralization but a delicate balance between these two dimensions. Together, interprets how efficiently resist meanwhile is maintained, emphasizing significance comprehensive assessment mutations.

Language: Английский

Citations

25
EG.5 (Eris) and BA.2.86 (Pirola) two new subvariants of SARS-CoV-2: a new face of old COVID-19 DOI

Abdolreza Esmaeilzadeh,

Fereshteh Ebrahimi, Armin Jahani Maleki

et al.

Infection, Journal Year: 2024, Volume and Issue: 52(2), P. 337 - 343

Published: Jan. 3, 2024

Language: Английский

Citations

8
SARS-CoV-2 Omicron: Viral Evolution, Immune Evasion, and Alternative Durable Therapeutic Strategies DOI Creative Commons
Hailong Guo, Sha Ha, Jason Botten

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(5), P. 697 - 697

Published: April 28, 2024

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns revoked all authorized immunotherapeutics. Rapid viral also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative understand how evolves into different subvariants causes escape as this could help reevaluate current intervention strategies mostly implemented clinics emergency measures counter pandemic and, importantly, develop new solutions. Here, we a review focusing on major events evolution, including features spike mutation that lead evasion against monoclonal antibody (mAb) therapy vaccination, suggest alternative durable options such ACE2-based experimental therapies superior mAbs address unprecedented virus. In addition, type unique virus-trapping molecules can zoonotic SARS coronaviruses, either from unknown animal hosts or established wild-life reservoirs SARS-CoV-2, even seasonal alpha coronavirus NL63 depends human ACE2 for infection.

Language: Английский

Citations

6
Comprehensive Analysis of Omicron Subvariants: EG.5 Rise, Vaccination Strategies, and Global Impact DOI

Debayan Sil,

Shreastha Gautam,

Shubhi Saxena

et al.

Current Drug Targets, Journal Year: 2024, Volume and Issue: 25(8), P. 517 - 525

Published: May 10, 2024

The emergence of new variants the SARS-CoV-2 virus during COVID-19 pandemic has prompted significant developments in understanding, monitoring, and response to these strains. This comprehensive review focuses on two prominent interest (VoI), XBB. 1.5 (Kraken) XBB.1.16 ("Arcturus"), along with seven under observation (VuM), including EG.5. World Health Organization (WHO) identified July 2023, highlighting EG.5's noteworthy rise prevalence. EG.5, also known as "Eris," exhibited an increased effective reproductive rate, prompting concerns about its contagiousness immune evasion capabilities. With altered spike protein Receptor-Binding Domain (RBD), EG.5 shares similarities XBB.1.5 but surpasses it prevalence, constituting 20% cases United States by late August. subvariant, EG.5.1, poses challenges mutations like Q52H F456L, contributing ability bypass neutralizing antibodies. global distribution presents a dynamic landscape, other strains gaining prominence. advent BA.2.86 variant further complicates scenario, notable spread regions lacking robust viral surveillance. A thorough analysis reveals evolving nature Omicron variant, distinct amino acid changes characterizing XBB.1.5, XBB.1.16, WHO designates "variant interest" due potential evasion, emphasizing need for vigilant monitoring. risk assessment underscores rapid development growing prevalence globally. While booster vaccines targeting are development, antiviral medications nirmatrelvir/ritonavir (Paxlovid) continue exhibit efficacy. In context variants, FDA granted emergency use authorization updated circulating strains, reflecting adaptability vaccination strategies address emerging challenges. overview provides nuanced understanding diverse subvariants, their impact, ongoing efforts combat through therapeutic interventions.

Language: Английский

Citations

3
The mutation point of view of the SARS‐CoV‐2 HV.1 lineage DOI
Alessandra Ciccozzi, Pier Luigi Fiori, Marco Casu

et al.

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(1)

Published: Jan. 1, 2024

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by authors. Any queries (other than missing content) should be directed to corresponding author article.

Language: Английский

Citations

3
Immunogenicity of Tetravalent Protein Vaccine SCTV01E-2 against SARS-CoV-2 EG.5 Subvaraint: A Phase 2 Trial DOI Creative Commons
Jihai Tang,

Qinghua Xu,

C. Zhu

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 175 - 175

Published: Feb. 8, 2024

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become the dominant strain. This phase 2 study aims evaluate immunogenicity SCTV01E-2, tetravalent protein vaccine, with specific emphasis its against EG.5, comparing it progenitor SCTV01E (NCT05933512). As 12 September 2023, 429 participants aged ≥18 years were randomized into groups (N = 215) and SCTV01E-2 214). Both vaccines showed increases in neutralizing antibody (nAb) 5.7-fold increase 9.0-fold 14 days post-vaccination, respectively. predetermined statistical endpoints achieved, showing that geometric mean titer (GMT) nAb seroresponse rate (SRR) significantly higher group than group. Additionally, induced 5.5-fold 5.9-fold XBB.1, Reactogenicity was generally mild transient. No vaccine-related serious adverse events (SAEs), special interest (AESIs), or deaths reported. In summary, elicited robust responses XBB.1 without raising safety concerns, highlighting potential as versatile COVID-19 vaccine variants.

Language: Английский

Citations

3
On the SARS-CoV-2 Variants DOI Creative Commons
Fabio Scarpa, Francesco Branda, Nicola Petrosillo

et al.

Infectious Disease Reports, Journal Year: 2024, Volume and Issue: 16(2), P. 289 - 297

Published: March 26, 2024

The evolutionary dynamics of viruses, particularly exemplified by SARS-CoV-2 during the ongoing COVID-19 pandemic, underscore intricate interplay between genetics, host adaptation, and viral spread. This paper delves into genetic evolution SARS-CoV-2, emphasizing implications variants on global health. Initially emerging from Wuhan-Hu-1 lineage, rapidly diversified numerous variants, each characterized distinct mutations in spike protein other genomic regions. Notable such as B.1.1.7 (α), B.1.351 (β), P.1 (γ), B.1.617.2 (δ), Omicron variant have garnered significant attention due to their heightened transmissibility immune evasion capabilities. In particular, has presented a myriad subvariants, raising concerns about its potential impact public Despite emergence vast majority exhibited limited expansion capabilities not posed threats akin early pandemic strains. Continued surveillance is imperative identify concern promptly. While adaptation intrinsic evolution, effective health responses must be grounded empirical evidence navigate evolving landscape with resilience precision.

Language: Английский

Citations

2
Immunogenicity of Tetravalent Protein Vaccine, SCTV01E-2 against SARS-CoV-2 EG.5 Subvaraint: a Phase 2 Trial DOI Open Access
Jihai Tang,

Qinghua Xu,

C. Zhu

et al.

Published: Dec. 15, 2023

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become dominant strain. This phase 2 study aims evaluate the immunogenicity SCTV01E-2, tetravalent protein vaccine, with specific emphasis its effectiveness against EG.5, comparing it progenitor SCTV01E (NCT05933512). As September 12, 2023, 429 participants aged ≥18 years were randomized (N=215) or SCTV01E-2 (N=214) groups. Both vaccines showed increases in neutralizing antibody (nAb) 5.7-fold increase and 9.0-fold groups 14 days post-vaccination, respectively. predetermined statistical endpoints achieved, showing that geometric mean titer (GMT) nAb seroresponse rate (SRR) significantly higher group compared SCTV01E. Additionally, induced 5.5-fold 5.9-fold XBB.1, Reactogenicity was generally mild transient. No vaccine related SAEs, AESIs deaths reported. In summary, elicited robust responses XBB.1 without safety concerns, underlining potential as versatile COVID-19 variants.

Language: Английский

Citations

4
Novel small-molecule inhibitors of SARS-CoV-2 main protease with nanomolar antiviral potency DOI Creative Commons

Haoran Zhang,

Kangping Zhou,

Fei Peng

et al.

Journal of Infection, Journal Year: 2024, Volume and Issue: 88(2), P. 211 - 214

Published: Jan. 6, 2024

Dear Editor, Recently, Saeed et al. reported the in silico screening of inhibitor molecules targeting SARS-CoV-2 main protease 3CLpro (also known as Nsp5 or Mpro) this Journal1Saeed Aamir Ahmad Basharat Majaz Sidra Nouroz Faisal Ashfaq Xie Yingqiu Targeting omicron and other lineages by potent inhibitors 3CL Mpro: Molecular simulation analysis.Journal Infection. 2022; 84: e133-e136https://doi.org/10.1016/j.jinf.2022.02.012Abstract Full Text PDF PubMed Scopus (2) Google Scholar. Despite progress, continuous emergence new viral variants highlights need for further antiviral drug development against SARS-CoV-2. After three years circulation human population, COVID-19 pandemic has evidently obtained heightened adaptability to humans. Although less virulent than original strain, like Omicron sublineage EG.5 acquired greater transmissibility possibly via adaptive evolution2Scarpa Fabio Pascarella Stefano Ciccozzi Alessandra Giovanetti Marta Azzena Ilenia Locci Chiara al.Genetic structural analyses reveal low potential variant.Journal Medical Virology. 2023; 95e29075https://doi.org/10.1002/jmv.29075Crossref (0) In light risk enhanced immune evasion such EG.53Zhang Lu Kempf Amy Nehlmeier Inga Cossmann Anne Dopfer-Jablonka Alexandra Stankov Metodi V. al.Neutralisation sensitivity EG.5.1 XBB.2.3.The Lancet Infectious Diseases. 23: e391-e392https://doi.org/10.1016/S1473-3099(23)00547-9Abstract (3) Scholar possible antigenic/virulent changes future, remains an urgent a critical component therapeutics. As cysteine hydrolase, cleaves polyproteins into functional non-structural proteins essential replication. Additionally, interrupts modulator nuclear factor-κB host brain endothelial cells, eliciting deleterious microvascular pathology4Wenzel Jan Lampe Josephine Müller-Fielitz Helge Schuster Raphael Zille Marietta Müller Kristin al.The Mpro causes pathology cleaving NEMO cells.Nat Neurosci. 2021; 24: 1522-1533https://doi.org/10.1038/s41593-021-00926-1Crossref (126) Notably, substrate-binding domain exhibits ultralow mutation rate 0.0015Gao Kaifu Wang Rui Chen Jiahui Tepe Jetze J. Huang Faqing Wei Guo-Wei Perspectives on Main Protease Inhibitors.J Med Chem. 64: 16922-16955https://doi.org/10.1021/acs.jmedchem.1c00409Crossref (56) Scholar, prospectively ensuring durable 3CLpro-targeting potency considering evolution. Collectively, conserved is promising strategy therapeutic development. Nirmatrelvir PF-07321332)6Owen Dafydd R. Allerton Charlotte M.N. Anderson Annaliesa S. Aschenbrenner Lisa Avery Melissa Berritt Simon al.An oral clinical candidate treatment COVID-19.Science. 374: 1586-1593https://doi.org/10.1126/science.abl4784Crossref (879) PaxlovidTM, highly covalent peptidomimetic inhibitor. By covalently binding catalytic Cys145 residue enabling additional non-covalent interactions hydrogen bonds hydrophobic contacts, nirmatrelvir effectively blocks replication suppressing proteolysis7Zhao Yao Fang Chao Zhang Qi Ruxue Zhao Xiangbo Duan Yinkai al.Crystal structure complex with PF-07321332.Protein & Cell. 13: 689-693https://doi.org/10.1007/s13238-021-00883-2Crossref (99) Combined ritonavir that does not act but Cyp P450 boost nirmatrelvir's exposure host, ameliorates patient symptoms reduces load. However, concerning rebound recurrent symptomatic infection frequently following therapy discontinuation8Wang Yu Xubo Xiao Wenying Danyang Feng Liuliu Rapid severe during 20-day course Paxlovid.Journal 85: e134-e136https://doi.org/10.1016/j.jinf.2022.08.012Abstract (15) Hence, optimizing compound imperative improve efficacy. Herein, we report several novel binder inhibit both enzymatic activity capability infect cells nanomolar inhibition potency. We identified six compounds inhibitors, namely AKEX0730, AKEX0736, AKEX0737, AKEX0763, AKEX0766, AKEX0806 (Fig. 1A). Initially, evaluated their activity. For comparison, nirmatrelvir6Owen served positive control. Relative nirmatrelvir, which showed half-maximal inhibitory concentration (IC50) 26.10 nM, all candidates exhibited low-nanomolar IC50 analogously superior 1B). Subsequently, characterized cytopathic effects HCoV-OC43 Vero E6 our nirmatrelvir. anticipated, (IC50 = 93.05 nM 543.5 SARS-CoV-2) cytotoxicity, validating assay reliability. Outstandingly, AKEX0763 proved most infections 326.1 5.352 HCoV-OC43), surpassing 1C-D). warrants investigation candidate. order better understand interaction between 3CLpro, first set out characterize properties N-terminal truncation (3CLpro-NTD). This truncated protein contains domains I II, where enzyme's active site located. Through microscale thermophoresis (MST) experiments, elucidated 3CLpro-NTD tight event 1E). To probe specifics interaction, next performed magnetic resonance (NMR) assays, can provide at level. recent study utilized direct transfer amide 1H-15N chemical shift assignments from SARS-CoV orthologous 3CLpro-NTD9Gao Jia Liang Liu Xiaodan Li Fudong Ma Rongsheng Zhu Zhongliang al.Repurposing Low-Molecular-Weight Drugs Severe Acute Respiratory Syndrome Coronavirus 2.J Phys Chem Lett. 2020; 11: 7267-7272https://doi.org/10.1021/acs.jpclett.0c01894Crossref was enabled extremely high sequence identity 96% these two proteases. experimentally validate transferred SARS-CoV-2, 3D heteronuclear NMR spectra, including HNCA 15N-edited NOESY-HSQC, sample. allowed us achieve partial 1H 15N resonances 2A). important control, compared HSQC spectra construct data full-length protein10Cantrelle François-Xavier Boll Emmanuelle Brier Lucile Moschidi Danai Belouzard Sandrine Landry Valérie al.NMR Spectroscopy Fragment-Based Screening Identify Three Protein Hotspots Antiviral Fragment.Angewandte Chemie International Edition. 60: 25428-25435https://doi.org/10.1002/anie.202109965Crossref (21) III driving dimerization. The overall agreement cross-peak signals datasets verified reliability assignments. With confidence 3CLpro-NTD, then conducted titration experiments 13C,15N-labeled unlabeled build upon MST results. Here, observed intensity reduction free-state peaks bound-state 2A), verifying regime slow exchange kinetics. Further analysis bound state revealed emerging exclusive matching characteristic pattern triple sequential peptide fragment Asp/Asn (49.2 ppm), Gly (42.3 Ser/Thr (59.0 ppm). cross-referencing tripeptide segments loss peak corresponding peaks, triplet assigned Asn142-Gly143-Ser144 2B). sequentially adjacent Cys145, predicted react similarly could be either free after iterating over unassigned peaks. may indicate intricate dynamics typically line broadening. specific involving solvent-exposed Asn142-Gly143-Ser144-Cys145 segment 2B-2C). residue-level mapping drug-target interface paves way rationale optimization next-generation instance, derivatization scaffold reinforce contact ones neighboring residues represents viable tactic enhancing Indeed, pathogenic variations across distinct geographical localities spotlights identifying elements amenable selective pharmacological interference are relatively conserved. presents irresistible target regard owing its indispensability directing maturation dissemination. biochemical intricacies underlying necessitate comprehensive elucidation isolates maximizing example, while shows remarkable pan-coronaviral converged engagements identical hotspot, subtype-specific customizations offer individual strains. Considering threat posed public health, structure-guided effort leveraging biochemical, biophysical, biology techniques delivered valuable mechanistic insights modalities formidable pathogen. exemplified quantitative assays herein, lead exhibit blocking viral-encoded functionally indispensable effectuating maturation. tight, structurally optimization. latest dominant have undergone antigenic drifts progressively eroding vaccine efficacy, extraordinarily conservation druggable hotspots ensures structure-informed continuing illuminate molecular interplay through state-of-the-art analytical approaches, repertoire agents will dramatically, accelerating advent efficacious, resistance-resilient regimens coronaviruses, Yan Li, Kun Cai, Gang Zou, Cheng Peng Jim Zhen Wu conceived project supervised research. Fei Haoran expressed purified proteins. Guowei Song, Mengfei Qian, Jin Wu, Fan Gao synthesized compounds. enzyme assays. Gao, Sophia Chun, analyzed data. Kangping Zhou, Bing Hu, Kai Pan, Meng Guo, Cai live virus neutralization Zhang, Peng, drafted revised manuscript. All authors contributed approved work funded National Key Research Development Program China (2022YFC2305500 2021YFC2600200 Y.L.), Hubei Provincial (2021ACB004 K.C.), General Natural Science Foundation (82372223 Public Health Outstanding Young Talents Project (to Y.L., Province Distinguished Scholars (2022CFA068 Y.L.).

Language: Английский

Citations

1
COVID -19: On the threshold of the fifth year. The situation in Spain DOI Creative Commons
Fernando Rodríguez‐Artalejo, Julián Ruiz‐Galiana, Rafael Cantón

et al.

Revista Española de Quimioterapia, Journal Year: 2023, Volume and Issue: 37(1), P. 17 - 28

Published: Nov. 27, 2023

Despite having emerged from pandemic status, the incidence of COVID-19 episodes has recently increased in Spain, including pediatric cases and admissions to Intensive Care Units. Several recombinant variants are circulating among us, particularly XBB arising two Omicron BA.2 sublineages with mutations genes encoding spicule proteins that could increase binding ACE2 receptor be more prone immune escape. Faced these, 3 pharmaceutical companies have developed vaccines adapted XBB.1.5 sublineage already available for administration our setting risks should not different those previous mRNA clearly favorable benefit/risk ratios. They applied patients potential poor evolution collectives a particular relationship proximity them. Their application understood only perspective individual convenience but also collective responsibility. The most convenient seems simultaneous immunization influenza environment. In therapeutic aspect, there is little expect right now antisera, known antiviral drugs still indicated, although their efficacy will reevaluated due impact on populations mostly immunized better prognosis than past. opinion, it necessary continue make reasonable timely use masks other non-pharmacological means protection.

Language: Английский

Citations

3