ETIDIOH - NEW

  Abstract The COVID-19 pandemic, driven by SARS-CoV-2, continues to challenge global health due to emerging variants and the potential risk posed by related sarbecoviruses . Neutralizing antibodies targeting the spike (S) glycoprotein, particularly the receptor-binding domain (RBD), play a crucial role in viral neutralization and vaccine design . Although broadly neutralizing anti-RBD antibodies have been identified, the nature of cross-reactive humoral responses induced by natural infection with ancestral SARS-CoV-2 strains remains incompletely understood. Here, we isolated 105 S-specific monoclonal antibodies (mAbs) from individuals recovered from prototype SARS-CoV-2 infection. Of these, 30 mAbs cross-recognized SARS-CoV-1 , including 25 RBD-directed mAbs, of which 12 displayed cross-neutralizing activity against both viruses . Among them, mAb 12C2 potently neutralized SARS-CoV-1 and multiple SARS-CoV-2 variants, likely through mechanisms that include inhibition of membrane fus...

  Abstract COVID-19 and long COVID are characterized by a dysregulated immune response. However, the role of macrophages during viral infection is poorly defined. Here we demonstrate that SARS-CoV-2 infection results in increased macrophage numbers and extensive formation of enlarged lipid-laden macrophages or foam cells using humanized mice , rhesus macaques and post-mortem human lung tissue . Notably, infection by other coronaviruses tested, SARS-CoV-1, MERS-CoV and two bat coronaviruses (SHC014-CoV or WIV1-CoV), did not result in macrophage proliferation or foam cell formation. Foam cells in SARS-CoV-2-infected human lung tissue display a pro-fibrotic and pro-thrombotic phenotype as they are enriched for genes associated with platelet activation and aggregation , as well as extracellular matrix organization and collagen synthesis . After viral clearance, macrophage numbers remain elevated, and lung fibrosis and thrombi persist . Importantly, we show that pre-exposure prophylaxis...

  Abstract SARS-CoV and MERS-CoV are two coronaviruses that have received significant attention due to their high pathogenicity and mortality rates in human populations . In this study, we compared their evolutionary dynamics to provide a One Health perspective on their differences in terms of the results of disease control. The phylogenetic network of SARS-CoVs showed that human isolates gathered into a “super-spreader” cluster and were distinct from civet isolates . In contrast, dromedary camel- and human-isolated MERS-CoVs were clustered together. Thus, most clades of MERS-CoV can infect humans , and MERS-CoVs seem to more easily spill over the animal-to-human interface. Additionally, the civet can be easily controlled , while the intermediate host (dromedary camels) of MERS-CoV is an important livestock species , so it is impossible to eliminate all animals. This further leads to difficulties in disease control in MERS. Although MERS-CoVs are endemic to dromedary camels in both...

Highlights •  Conserved T cell epitope regions elicit strong CD4+ and CD8+ T cell responses in SARS2-exposed •  CTERs enhance cross-reactivity across multiple Betacoronaviruses •  Targeting non-spike proteins expands immune breadth and HLA coverage •  Removing low population coverage regions preserves cross-reactivity Summary The COVID-19 pandemic highlighted the critical need for vaccine strategies capable of addressing emerging viral threats . Betacoronaviruses, including severe acute respiratory syndrome coronavirus ( SARS-CoV ), Middle East respiratory syndrome ( MERS ), and SARS-CoV-2 , present significant pandemic risks due to their zoonotic potential and genetic diversity . T cell-mediated immunity has demonstrated durable responses and strong cross-reactivity, offering a promising avenue for achieving broad immunity within a viral family. In this study, we combined comprehensive epitope mapping with sequence conservation analyses to identify conserved T cell ...

Abstract We sequenced sarbecovirus from Rhinolophus spp. bats in Bandarban District , Bangladesh, in a genomic surveillance campaign during 2022–2023. Sequences shared identity with SARS-CoV-1 Tor2, which caused an outbreak of human illnesses in 2003 . Describing the genetic diversity and zoonotic potential of reservoir pathogens can aid in identifying sources of future spillovers. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/8/25-0071_article ____

Abstract The coronavirus membrane protein (M) is the main organizer of coronavirus assembly. Here, we report on an M-targeting molecule , CIM-834, that blocks the assembly of SARS-CoV-2. CIM-834 was obtained through high-throughput phenotypic antiviral screening followed by medicinal-chemistry efforts and target elucidation. CIM-834 inhibits the replication of SARS-CoV-2 (including a broad panel of variants) and SARS-CoV. In SCID mice and Syrian hamsters intranasally infected with SARS-CoV-2, oral treatment reduced lung viral titres to nearly undetectable levels, even (as shown in mice) when treatment was delayed until 24 h before the end point. Treatment of infected hamsters prevented transmission to untreated sentinels. Transmission electron microscopy studies show that virion assembly is completely absent in cells treated with CIM-834. Single-particle cryo-electron microscopy reveals that CIM-834 binds and stabilizes the M protein in its short form, thereby preventing the conformati...

ABSTRACT The evolution of the antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is impacted by the nature and number of antigenic exposures . First-generation coronavirus disease 2019 (COVID-19) vaccines encoded an ancestral spike protein . Updated bivalent vaccines and breakthrough infections have shaped the intricate diversity of the polyclonal antibody response and specificity of individual antibody clones. We and others previously showed that bivalent vaccines containing the ancestral and Omicron (BA.5) spikes induce high levels of cross-reactive antibodies but undetectable BA.5-specific antibodies in serum. Here, we assessed sera collected before as well as 1 and 3 months following administration of an updated XBB.1.5 monovalent vaccine to individuals with diverse infection and vaccination histories. Vaccination increased neutralization against recent variants of concern , including HV.1, JN.1 , and the vaccine-homologous XBB.1.5. Antibody bindi...