A COVID-19 booster dose has been found to be effective in our fight against SARS-CoV-2 infection. However, their long-term beneficial or adverse effects among healthy individuals are not fully understood. We investigated the impact of the Pfizer-BioNTech-(BNT162b2) booster dose on plasma proteome profiles of fully vaccinated healthy individuals in a mimic of reinfection to understand the disease mechanisms and to identify novel diagnostic and prognostic biomarkers. In contrast to prebooster, postbooster recipients exhibited a distinct proteomic signature following SARS-CoV-2 spike (S) protein stimulation. The gene ontology (GO) terms of biological processes revealed the five most significant functions enriched in stress and immune responses, especially via complement and blood coagulation systems. Likewise, the Reactome pathway demonstrated significant activation of complement cascade, platelet degranulation, and innate immune systems. Moreover, the protein-protein interaction network exhibited regulation of body fluid levels and acute inflammatory response. In summary, our study identified abundant dysregulated signatures predominantly associated with the complement, the innate immune system, and platelet degranulation. Besides eliciting humoral immunity, our study also found key proteins involved in blood coagulation pathways that could perhaps shed light on individuals exhibiting comorbidities associated with COVID-19 vaccination. Therefore, factors dysregulated following SARS-CoV-2 spike (S) protein stimulation may provide insights into pathways potentially implicated in post-vaccination reactions.

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus that can cause zoonotic disease in humans with lethal severe viral pneumonia. Dromedary camels are the source of zoonotic infection. As of November 2025, MERS-CoV has resulted in a total of 2630 reported cases, 37% of these being fatal. The number of reported human cases has been on a decreasing trend since 2016 and reached a nadir during the COVID-19 pandemic. The reason for the reduction of cases is unclear and may be multifactorial. We hypothesized that mutations accumulating in the virus spike protein may have reduced zoonotic potential. Here, we investigate the impact of recently emerged virus spike-protein mutations on virus replication competence using pseudoviruses and replication-competent recombinant viruses. We found that virus spike variants detected in 2019 and some from 2023 show a reduced cell entry, lower viral replication and reduced fitness in human primary alveolar epithelial cells and multiple cell lines. All the MERS-CoV spikes tested showed a cell-entry pathway preference via the cell-surface TMPRSS2 route. Mechanistically, we showed the V530A mutation in the 2019 spike sequence had a reduced human DPP4 binding phenotype. Our data highlighted MERS-CoV spike mutations can modulate viral fitness in human cells and provide new insights to understand recent MERS epidemiology.

As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies. To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion. This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, at 26 hospitals in 20 US states. Case patients presented with COVID-19-like illness and positive SARS-CoV-2 nucleic acid or antigen test results; control patients had COVID-19-like illness but tested negative for SARS-CoV-2. Receipt of a 2024-2025 COVID-19 vaccine at least 7 days before illness onset. Main outcomes were COVID-19-associated hospitalization and severe in-hospital outcomes (supplemental oxygen therapy, acute respiratory failure, intensive care unit admission, and invasive mechanical ventilation or death). Logistic regression was used to estimate the odds of vaccination in case and control patients, adjusting for demographics, clinical characteristics, and enrollment region. The VE was estimated as (1 - adjusted odds ratio) × 100%. A total of 8493 patients (median [IQR] age, 66 [54-76] years; 4338 female [51.1%]), including 1888 case patients with COVID-19 (among whom 951 [50.4%] had successful whole-genome sequencing, including 348 [36.6%] with KP.3.1.1, 218 [22.9%] with XEC, and 134 [14.1%] with LP.8.1 infections) and 6605 control patients were enrolled. Vaccine effectiveness against COVID-19-associated hospitalization was 40% (95% CI, 27%-51%), and protection was sustained through 90 to 179 days after vaccination. Vaccine effectiveness was higher against the most severe outcome of invasive mechanical ventilation or death at 79% (95% CI, 55%-92%). It was 49% (95% CI, 25%-67%) against hospitalization with KP.3.1.1, 34% (95% CI, 4%-56%) against XEC, and 24% (95% CI, -19% to 53%) against LP.8.1, with increasing median time since dose receipt among vaccinated case patients due to sequential circulation patterns (60, 89, and 141 days, respectively). The VE was similar against lineages with spike protein S31 deletion (41% [95% CI, 22%-56%]) and T22N and F59S substitutions (37% [95% CI, 9%-57%]). In this multicenter, case-control analysis of VE, 2024-2025 COVID-19 vaccines may have provided protection against hospitalizations and severe in-hospital outcomes as multiple JN.1 descendant lineages circulated. Monitoring COVID-19 VE, including stratifying by SARS-CoV-2 lineage and spike protein mutations, remains important to guide COVID-19 vaccine composition and recommendations.

Bioactive galloylquinic acids from Copaifera lucens as dual inhibitors of SARS-CoV-2 Spike and RdRp proteins

Ultra-diluted Bryonia alba extract modulates HMOX-1 gene expression to attenuate the pathogenetic effect of SARS-CoV-2 spike protein RBD antigen.

Humoral and cellular immunogenicity of sequential heterogeneous bivalent SARS-CoV-2 vaccinations in long-term care and retirement home residents.

SARS-CoV-2 inhibition through mRNA delivery using engineered extracellular vesicles displaying the spike protein.

ACE2 inhibition ELISA is an effective surrogate for SARS-CoV-2 live virus neutralisation.

Spumigins produced by Nodularia spumigena are natural serine protease inhibitors with anti-SARS-CoV-2 activity.

Post COVID-19 pandemic Inflammatory Insights into Cancer: Consequences for immunotherapy.

Insights into antiviral activity of chlorpromazine against RNA viruses: Molecular docking, ADME profile, and semi-in vivo study.

Antibody escape of SARS-CoV-2 variants of concern on receptor-binding domain: A computational approach.

The efficacy of nucleic acid-based vaccines against SARS-CoV-2 varies across individuals, partly due to genetic factors influencing neutralizing antibody production. In patients with systemic autoimmune diseases (SADs), this response may be further altered by immune dysregulation. We conducted a genome-wide association study (GWAS) to identify genetic variants associated with postvaccination anti-SARS-CoV-2 IgG antibody levels and to assess whether these associations differ between patients with SAD and healthy individuals. The study included 165 participants (138 with SADs, 27 healthy controls), all of whom received nucleic acid-based vaccines. Antibody levels targeting the spike protein receptor-binding domain (RBD) and nucleocapsid were measured between 1 and 12 months after vaccination. GWAS results were metaanalyzed with data from a previously published GWAS with 1076 healthy individuals. We identified a novel association near RACGAP1 (rs706785; βmeta = -0.30, P meta = 3.85 × 10-8) and replicated a known association at HLA-DRB1 position 71 (βmeta = -0.23, P meta = 1.94 × 10-11). No significant interactions were observed between genotype and disease status. This study highlights both MHC and non-MHC genetic contributions to SARS-CoV-2 vaccine responses and suggests these effects are consistent across patients with SADs and healthy individuals, supporting standard vaccination strategies for individuals with systemic autoimmune conditions.

SARS-CoV-2 Spike displays multiple adaptive changes in addition to the furin cleavage site.

Forsythoside A inhibits avian infectious bronchitis virus infection by binding the S1 subunit.

Viral traits from deep mutational scanning and socio-demographic context predict SARS-CoV-2 lineage fitness across diverse countries.

The study investigates temporin-derived antimicrobial peptides as broad-spectrum antiviral candidates against SARS-CoV-2. Surface plasmon resonance screening shows that temporin G (TG), temporin L (TL), and the nonhemolytic analog Pro3-TL bind the trimeric Spike protein with high affinity, following a two-state binding model. NMR confirms TG-Spike interactions and identifies Phe2 as critical for binding. Docking simulations place the interaction at the NTD-RBD interface and reveal a cation-π interaction between TG Phe2 and Spike Arg357. These insights informed the design of the chimeric analog RB-142 and four derivatives (RB-143 to RB-146) incorporating bulkier aromatic residues. All analogs exhibit submicromolar binding affinities. Biological assays show low cytotoxicity and potent virucidal activity, with RB-146 demonstrating the strongest effect and a high therapeutic index. Mechanistic analyses indicate that RB-146 disrupts viral attachment and damages the viral envelope. The findings position RB-146 as a promising dual-mechanism antiviral candidate.

A colloidal gold immunochromatographic test strip based on mAbs anti-S protein to detect porcine deltacoronavirus.

Integrated optical and acoustic detection of SARS-CoV-2 spike anti-RBD antibodies using secondary antibodies and gold nanoparticles.

Effective respiratory mucosal vaccines remain urgently needed to mitigate the rapid mutation and transmission of SARS-CoV-2. Here, we demonstrated that the spike protein (S-2P) of ancestral SARS-CoV-2 acted as a self-adjuvanted antigen for intranasal immunization, inducing robust systemic and mucosal immunity via integrin- and STING-dependent pathways. In contrast, H1N1 influenza hemagglutinin (HA) failed to generate measurable serum IgG or mucosal IgA following intranasal immunization. In mice, intranasal S-2P vaccination conferred complete protection against lethal ancestral SARS-CoV-2 challenge and partial cross-protection against heterologous Omicron variants, with both effects being IFN-γ- and CD8 + T cell-dependent. Co-administration of S-2P with the clinical immunomodulator lentinan (LNT) achieved complete protection against Omicron variants, mediated by IFN-γ but largely independent of CD8 + T cells. These findings establish S-2P + LNT as a safe, broad-spectrum mucosal vaccine candidate against emerging SARS-CoV-2 variants and reveal novel protection mechanisms beyond neutralizing antibodies and T cell immunity.