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

Advances in the development of infectious clones of human coronaviruses and related applications DOI Creative Commons
Guangya Liu, Rayner Kay Jin Tan, Yiyi Wu

et al.

Biosafety and Health, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Broad host tropism of ACE2-using MERS-related coronaviruses and determinants restricting viral recognition DOI Creative Commons

Chengbao Ma,

Chen Liu, Qing Xiong

et al.

Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: June 15, 2023

Recently, two Middle East respiratory syndrome coronavirus (MERS-CoV) closely related to bat merbecoviruses, NeoCoV and PDF-2180, were discovered use angiotensin-converting enzyme 2 (ACE2) for entry. The viruses cannot human ACE2 efficiently, their host range cross-species transmissibility across a wide of mammalian species remain unclear. Herein, we characterized the species-specific receptor preference these by testing orthologues from 49 bats 53 non-bat mammals through receptor-binding domain (RBD)-binding pseudovirus entry assays. Results based on revealed that unable most, but not all, Yinpterochiropteran (Yin-bats), which is distinct NL63 SARS-CoV-2. Besides, both exhibited broad recognition spectra mammals. Genetic structural analyses highlighted four crucial determinants, all confirmed subsequent functional assays in cells. Notably, residue 305, participating critical viral interaction, plays role tropism determination, particularly Furthermore, PDF-2180 mutants with enhanced expanded potential range, especially enhancing interaction an evolutionarily conserved hydrophobic pocket. Our results elucidate molecular basis usage MERS-related shed light zoonotic risks.

Language: Английский

Citations

18
Emergence and spread of feline infectious peritonitis due to a highly pathogenic canine/feline recombinant coronavirus DOI Creative Commons
Charalampos Attipa, Amanda Warr, Demetris Epaminondas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 9, 2023

Abstract Cross-species transmission of coronaviruses (CoVs) poses a serious threat to both animal and human health 1–3 . Whilst the large RNA genome CoVs shows relatively low mutation rates, recombination within genera is frequently observed demonstrated 4–7 Companion animals are often overlooked in cycle viral diseases; however, close relationship feline (FCoV) canine CoV (CCoV) hCoV-229E 5,8 , as well their susceptibility SARS-CoV-2 9 highlight importance potential cycles. between CCoV FCoV fragment spanning orf1b M has been previously described 5,10 here we report emergence novel, highly pathogenic FCoV-CCoV recombinant responsible for rapidly spreading outbreak infectious peritonitis (FIP), originating Cyprus 11 The minor region, spike (S), 96.5% sequence identity pantropic coronavirus NA/09. Infection spread, infecting cats all ages. Development FIP appears very frequent identities samples from different districts island strongly supportive direct transmission. A near cat-specific deletion domain 0 S present >90% cats. It unclear yet whether this directly associated with disease development may be linked biotype switch 12 several amino acid changes S, particularly receptor binding domain, indicate cell tropism.

Language: Английский

Citations

17
Human coronavirus HKU1 recognition of the TMPRSS2 host receptor DOI Creative Commons
Matthew McCallum, Young‐Jun Park, Cameron Stewart

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 9, 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. Here, we designed an active construct enabling high-yield recombinant production in cells this key therapeutic target. We determined a cryo-electron microscopy structure the RBD bound providing blueprint interactions supporting viral entry explaining specificity for among type proteases. found that human, rat, hamster camel promote S-mediated into identified residues governing usage. Our data show serum antibodies targeting binding-site are neutralization uses conformational masking glycan shielding balance immune evasion engagement.

Language: Английский

Citations

8
Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans DOI Creative Commons
David Chmielewski, Eric Wilson, Grigore Pintilie

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 7, 2023

Abstract Coronavirus spike glycoproteins presented on the virion surface mediate receptor binding, and membrane fusion during virus entry constitute primary target for vaccine drug development. How structure dynamics of full-length spikes incorporated in viral lipid envelope correlates with infectivity remains poorly understood. Here we present structures distributions native conformations vitrified human coronavirus NL63 (HCoV-NL63) virions without chemical fixation by cryogenic electron tomography (cryoET) subtomogram averaging, along site-specific glycan composition occupancy determined mass spectrometry. The higher oligomannose shield HCoV-NL63 than SARS-CoV-2 stronger immune evasion HCoV-NL63. Incorporation cryoET-derived into all-atom molecular dynamic simulations elucidate conformational landscape glycosylated, that reveals a role hinge glycans modulating bending. We show glycosylation at N1242 upper portion stalk is responsible extensive orientational freedom crown. Subsequent assays implicated involvement N1242-glyan entry. Our results suggest potential therapeutic site

Language: Английский

Citations

16
Towards a Safer Future: Enhancing Vaccine Development to Combat Animal Coronaviruses DOI Creative Commons
Fusheng Si,

Ruisong Yu,

Shijuan Dong

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(3), P. 330 - 330

Published: March 19, 2024

Coronaviruses (CoVs) are a large class of positively stranded RNA viruses that pose significant threat to public health, livestock farming, and wild animals. These have the ability cross species barriers cause devastating epidemics. Animals considered be intermediate hosts for many coronaviruses, animal coronaviruses also potential cross-species transmission humans. Therefore, controlling epidemic is great importance human health. Vaccination programs proven effective in infections, offering cost-effective approach reducing morbidity mortality, so re-emergence lethal emphasizes urgent need development vaccines. In this regard, we explore progress coronavirus vaccine development, covering latest taxonomy main spillover events, diverse platforms, targets primary challenges facing We emphasize create “dual-effect” capable eliciting both cellular humoral immune responses. The goal highlight contributions veterinary scientists field interdisciplinary collaboration between medical communities. By promoting communication cooperation, can enhance novel super vaccines combat infections future.

Language: Английский

Citations

6
ACE2-using merbecoviruses: Further evidence of convergent evolution of ACE2 recognition by NeoCoV and other MERS-CoV related viruses DOI Creative Commons
Qing Xiong,

Chengbao Ma,

Chen Liu

et al.

Cell Insight, Journal Year: 2024, Volume and Issue: 3(1), P. 100145 - 100145

Published: Jan. 30, 2024

Angiotensin-converting enzyme 2 (ACE2) was recognized as an entry receptor shared by coronaviruses from

Language: Английский

Citations

5
Selection and design principle of efficient antiviral nano-hybrid fiber materials for fighting pandemic viruses: A review DOI
Guoyin Chen,

Lijun Yang,

Ning Ma

et al.

Nano Today, Journal Year: 2023, Volume and Issue: 53, P. 102001 - 102001

Published: Sept. 26, 2023

Language: Английский

Citations

12
Persistent immune imprinting after XBB.1.5 COVID vaccination in humans DOI Creative Commons
M. Alejandra Tortorici, Amin Addetia,

Albert J. Seo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 30, 2023

Immune imprinting - also known as ‘original antigenic sin’ describes how the first exposure to a virus shapes immunological outcome of subsequent exposures antigenically related strains. SARS-CoV-2 Omicron breakthrough infections and bivalent COVID-19 vaccination were shown primarily recall cross-reactive memory B cells antibodies induced by prior mRNA with Wuhan-Hu-1 spike rather than priming naive that recognize Omicron-specific epitopes. These findings underscored strong immune resulting from repeated exposures. To understand if can be overcome, we investigated plasma antibody responses after administration updated XBB.1.5 COVID vaccine booster. Our data show booster elicits neutralizing against current variants are dominated pre-existing previously spike. results indicate persists even multiple spikes through infection, including post vaccination, which will need considered guide design future boosters.

Language: Английский

Citations

12
Serial cell culture passaging in vitro led to complete attenuation and changes in the characteristic features of a virulent porcine deltacoronavirus strain DOI Creative Commons
Ping Zhang, Ruiming Yu, Lianshun Wang

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(8)

Published: July 16, 2024

ABSTRACT Porcine deltacoronavirus (PDCoV) is an important enteric coronavirus that has caused enormous economic losses in the pig industry worldwide. However, no commercial vaccine currently available. Therefore, developing a safe and efficacious live-attenuated candidate urgently needed. In this study, PDCoV strain CH/XJYN/2016 was continuously passaged LLC-PK cells until passage 240, virus growth kinetics cell culture, pathogenicity neonatal piglets, transcriptome differences after infection, changes functional characteristics of spike (S) protein high- low-passage strains, genetic variation genome, resistance to pepsin acid, protective effects when used as were examined. The results animal experiments demonstrated virulent completely attenuated not pathogenic piglets following serial passage. Genome sequence analysis showed amino acid mutations nonstructural proteins mainly concentrated Nsp3, structural S protein, N, M, E genes conserved. Transcriptome comparison revealed compared with negative control cells, P10-infected had most differentially expressed (DEGs), while P0 P240 least number DEGs. Analysis trypsin dependence related P10 interacted more strongly P120 APN receptor. Moreover, infectivity affected by but significantly decreased exposure low pH. Furthermore, P240-based provided complete protection against challenge PDCoV. conclusion, we through passaging vitro . These provide insights into potential molecular mechanisms attenuation development promising vaccine. IMPORTANCE one enteropathogenic pathogens cause diarrhea pigs various ages, especially suckling causes global pork industry. There are effective measures prevent As reported previous porcine epidemic (PEDV) transmissible gastroenteritis studies, inactivated vaccines usually elicit less robust immune responses than native sows. identifying mechanisms, gene evolution, during passaging, immunogenicity for elucidating mechanism strains. virulence , biological efficacy evaluated. Our help elucidate support appropriate designs study live vaccines.

Language: Английский

Citations

4