Molecular basis of host recognition of human coronavirus 229E DOI Creative Commons
Yu-Xi Tsai, Yu-Chun Chien, Min‐Feng Hsu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 27, 2025

Human coronavirus 229E (HCoV-229E) is the earliest CoV found to infect humans. It binds human aminopeptidase N (hAPN) through receptor binding domain (RBD) of its spike (S) protein achieve host recognition. We present cryo-electron microscopy structure two HCoV-229E S in complex with a dimeric hAPN provide structural insights on how opens up RBD engage receptor, information that currently missing among alphacoronaviruses which belong. quantitatively profile glycosylation and deduce glyco-shielding effects pertinent antigenicity Finally, we an atomic model fully glycosylated anchored their respective membrane bilayers recapitulate basis first step infection by HCoV-229E. (hCoV-229E) identified coronaviruses. Here, authors use cryo-EM, glycoproteomics, modeling determine glycosylated, membrane-bound hCoV-229E

Language: Английский

ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies DOI Creative Commons
Jun Siong Low, Josipa Jerak, M. Alejandra Tortorici

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6607), P. 735 - 742

Published: July 12, 2022

The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind all human-infecting proteins from severe acute respiratory syndrome 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide acquire affinity breadth through somatic mutations. Despite targeting conserved motif, only some show neutralizing activity in vitro against alpha- betacoronaviruses, including animal coronaviruses WIV-1 PDF-2180. Two selected also neutralize Omicron BA.1 BA.2 authentic viruses reduce burden pathology vivo. Structural functional analyses showed peptide–specific bound with different modalities cryptic epitope hidden prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme (ACE2) or ACE2-mimicking mAbs.

Language: Английский

Citations

146
Close relatives of MERS-CoV in bats use ACE2 as their functional receptors DOI Creative Commons
Qing Xiong, Lei Cao,

Chengbao Ma

et al.

Nature, Journal Year: 2022, Volume and Issue: 612(7941), P. 748 - 757

Published: Dec. 7, 2022

Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor1-4. However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear5. Here, using a pseudotype virus assay, we that NeoCoV its close relative, PDF-2180, can efficiently bind to specific angiotensin-converting enzyme 2 (ACE2) orthologues and, less favourably, human ACE2 receptors through their receptor-binding domains (RBDs) on spike (S) proteins. Cryo-electron microscopy analysis revealed RBD-ACE2 binding interface involving protein-glycan interactions, distinct from those of other ACE2-using coronaviruses. We identified residues 337-342 molecular determinant restricting entry, whereas S pseudotyped containing T510F RBD mutation entered cells expressing ACE2. Although polyclonal SARS-CoV-2 antibodies or RBD-specific nanobodies did not cross-neutralize ACE2-specific antibody two broadly neutralizing betacoronavirus inhibited these viruses. describe MERS-CoV-related viruses receptor, underscoring promiscuity potential zoonotic threat.

Language: Английский

Citations

104
Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein DOI Creative Commons
Filippo Bianchini, Virginia Crivelli, Morgan E. Abernathy

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(81)

Published: Jan. 26, 2023

Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy vaccines and antiviral monoclonal antibodies. Continued development immunotherapies vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions virus spike glycoprotein are both functionally relevant averse change, we identified human neutralizing antibodies highly conserved epitopes. Antibody fp.006 binds fusion peptide cross-reacts against coronaviruses four genera, including nine coronaviruses, through recognition motif includes S2' site proteolytic cleavage. hr2.016 targets stem helix neutralizes SARS-CoV-2 variants. sd1.040 subdomain 1, synergizes with rbd.042 for neutralization, and, similar hr2.016, protects mice expressing angiotensin-converting enzyme infection when present as bispecific antibody. Thus, discovery reveals donor-derived cross-reactive Orthocoronavirinae,

Language: Английский

Citations

67
Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans DOI Creative Commons
M. Alejandra Tortorici, Amin Addetia,

Albert J. Seo

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 904 - 911.e4

Published: March 14, 2024

Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA rather than priming Omicron-specific naive cells. These findings indicate that immune occurs after repeated exposures, but whether it can be overcome remains unclear. To understand persistence imprinting, we investigated plasma antibody responses administration updated XBB.1.5 vaccine booster. We showed booster elicited neutralizing against current variants were dominated pre-existing previously spike. Therefore, persists multiple spikes through infection, including post vaccination, which will need considered guide future vaccination.

Language: Английский

Citations

57
Farmed fur animals harbour viruses with zoonotic spillover potential DOI
Jin Zhao,

Wenbo Wan,

Yu Kang

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8032), P. 228 - 233

Published: Sept. 4, 2024

Language: Английский

Citations

22
Human coronavirus HKU1 recognition of the TMPRSS2 host receptor DOI Creative Commons
Matthew McCallum, Young‐Jun Park, Cameron Stewart

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(16), P. 4231 - 4245.e13

Published: July 3, 2024

The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. molecular basis of binding TMPRSS2 determinants receptor tropism remain elusive. We designed an active construct enabling high-yield recombinant production in cells this key therapeutic target. determined a cryo-electron microscopy structure the RBD bound TMPRSS2, providing blueprint interactions supporting viral entry explaining specificity for among orthologous proteases. identified orthologs from five mammalian orders promoting S-mediated into along with residues governing usage. Our data show that motif is site vulnerability neutralizing antibodies suggest uses S conformational masking glycan shielding balance immune evasion engagement.

Language: Английский

Citations

16
Multiple independent acquisitions of ACE2 usage in MERS-related coronaviruses DOI Creative Commons

Chengbao Ma,

Chen Liu, Young‐Jun Park

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

The angiotensin-converting enzyme 2 (ACE2) receptor is shared by various coronaviruses with distinct receptor-binding domain (RBD) architectures, yet our understanding of these convergent acquisition events remains elusive. Here, we report that two bat MERS-related (MERSr-CoVs) infecting Pipistrellus nathusii (P.nat)-MOW15-22 and PnNL2018B-use ACE2 as their receptor, narrow ortholog specificity. Cryoelectron microscopy structures the MOW15-22/PnNL2018B RBD-ACE2 complexes unveil an unexpected entirely binding mode, mapping >45 Å away from any other known ACE2-using coronaviruses. Functional profiling orthologs 105 mammalian species led to identification host tropism determinants, including N432-glycosylation restricting viral recognition, design a soluble P.nat mutant potent neutralizing activity. Our findings reveal usage for merbecoviruses found in European bats, underscoring extraordinary diversity recognition modes among promiscuity this receptor.

Language: Английский

Citations

5
Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses DOI
Young‐Jun Park, Chen Liu, Jimin Lee

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

5
Transmissible Gastroenteritis Virus: An Update Review and Perspective DOI Creative Commons

Yiwu Chen,

Yuan‐Zhu Zhang, Xi Wang

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 359 - 359

Published: Jan. 27, 2023

Transmissible gastroenteritis virus (TGEV) is a member of the alphacoronavirus genus, which has caused huge threats and losses to pig husbandry with 100% mortality in infected piglets. TGEV observed be recombining evolving unstoppably recent years, some these recombinant strains spreading across species, makes detection prevention more complex. This paper reviews discusses basic biological properties TGEV, factors affecting virulence, viral receptors, latest research advances infection-induced apoptosis autophagy improve understanding current status related processes. We also highlight possible risk being zoonotic, could evidenced by CCoV-HuPn-2018 humans.

Language: Английский

Citations

31
A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification DOI Creative Commons
Laura E. Rosen, M. Alejandra Tortorici, Anna De Marco

et al.

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing sufficiently potent clinical development and retain activity despite remain elusive. We identified human mAb, designated VIR-7229, which targets the receptor-binding motif (RBM) with unprecedented cross-reactivity all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently SARS-CoV-2 variants since 2019, recent EG.5, BA.2.86, JN.1. VIR-7229 tolerates extraordinary variability, partly attributed its high binding affinity, receptor molecular mimicry, interactions RBM backbone atoms. Consequently, features barrier selection of mutants, rare associated reduced fitness, underscoring potential be future evolution. is strong candidate become next-generation medicine.

Language: Английский

Citations

10