Mechanisms of SARS-CoV-2 entry into cells

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 3 - 20

Published: Oct. 5, 2021

Language: Английский

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Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses

Cell, Journal Year: 2021, Volume and Issue: 184(17), P. 4380 - 4391.e14

Published: June 9, 2021

Language: Английский

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RING 3.0: fast generation of probabilistic residue interaction networks from structural ensembles

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 50(W1), P. W651 - W656

Published: April 30, 2022

Abstract Residue interaction networks (RINs) are used to represent residue contacts in protein structures. Thanks the advances network theory, RINs have been proved effective as an alternative coordinate data analysis of complex systems. The RING server calculates high quality and reliable non-covalent molecular interactions based on geometrical parameters. Here, we present new 3.0 version extending previous functionality several ways. underlying software library has re-engineered improve speed by order magnitude. now also supports mmCIF format provides typed for entire PDB chemical component dictionary, including nucleic acids. Moreover, employs probabilistic graphs, where multiple conformations (e.g. NMR or dynamics ensembles) mapped weighted edges, opening up ways analyze structural data. web interface expanded include a simultaneous view RIN alongside structure viewer, with both synchronized clickable. Contact evolution across models (or time) is displayed heatmap can help discovery correlating patterns. server, together extensive tutorial, available from URL: https://ring.biocomputingup.it/.

Language: Английский

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Close relatives of MERS-CoV in bats use ACE2 as their functional receptors

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

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Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses

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

Published: Feb. 1, 2025

Language: Английский

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Multiple independent acquisitions of ACE2 usage in MERS-related coronaviruses

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

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Predicting the zoonotic capacity of mammals to transmit SARS-CoV-2

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2021, Volume and Issue: 288(1963)

Published: Nov. 17, 2021

Back and forth transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between humans animals will establish wild reservoirs virus that endanger long-term efforts to control COVID-19 in people protect vulnerable animal populations. Better targeting surveillance laboratory experiments validate zoonotic potential requires predicting high-risk host species. A major bottleneck this effort is the few species with available sequences for angiotensin-converting enzyme receptor, a key receptor required viral cell entry. We overcome by combining species' ecological biological traits three-dimensional modelling host-virus protein-protein interactions using machine learning. This approach enables predictions about capacity SARS-CoV-2 greater than 5000 mammals-an order magnitude more previously possible. Our are strongly corroborated vivo studies. The predicted proximity suggest enhanced risk from several common mammals, priority areas geographic overlap these global hotspots. With molecular data only small fraction hosts, linking across scales offers conceptual advance may expand our predictive viruses similarly unknown ranges.

Language: Английский

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COVID-19 and SARS-CoV-2 Variants: Current Challenges and Health Concern

Frontiers in Genetics, Journal Year: 2021, Volume and Issue: 12

Published: June 15, 2021

The ongoing coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, was triggered and unfolded quickly throughout the globe by severe acute respiratory syndrome 2 (SARS-CoV-2). new virus, transmitted primarily through inhalation or contact with infected droplets, seems very contagious pathogenic, an incubation period varying from to 14 days. epidemic is public health problem that challenges present global system. A worldwide social economic stress has been observed. transitional source of origin its transport humans unknown, but speedy human transportation accepted extensively. typical clinical symptoms COVID-19 are almost like colds. With case fatality rates 3 percent, a small number patients may experience serious problems even die. To date, there limited antiviral agents vaccines for treatment COVID-19. occurrence pathogenicity infection outlined comparatively analyzed, given outbreak’s urgency. recent developments diagnostics, treatment, marketed vaccine discussed deal this viral outbreak. Now scientist concerned about appearance several variants over efficacy against these variants. There need consistent monitoring virus epidemiology surveillance variant related severity.

Language: Английский

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Emerging SARS-CoV-2 variants: Why, how, and what's next?

Cell Insight, Journal Year: 2022, Volume and Issue: 1(3), P. 100029 - 100029

Published: May 2, 2022

The emergence of the SARS-CoV-2 Omicron variant poses a striking threat to human society. More than 30 mutations in Spike protein severely compromised protective immunity elicited by either vaccination or prior infection. persistent viral evolutionary trajectory generates Omicron-associated lineages, such as BA.1 and BA.2. Moreover, virus recombination upon Delta co-infections has been reported lately, although impact remains be assessed. This minireview summarizes characteristics, evolution mutation control, immune evasion mechanisms variants, which will helpful for in-depth understanding variants policy-making related COVID-19 pandemic control.

Language: Английский

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Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s

Cell Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: July 12, 2022

The Omicron variant of SARS-CoV-2 carries multiple unusual mutations, particularly in the receptor-binding domain (RBD) spike (S) protein. Moreover, host-adapting such as residues 493, 498, and 501, were also observed RBD, which indicates that it is necessary to evaluate interspecies transmission risk variant. Herein, we evaluated recognition BA.1 Delta RBDs by 27 ACE2 orthologs, including humans. We found expanded its receptor binding spectra palm-civet, rodents, more bats (least horseshoe bat greater bat) lesser hedgehog tenrec. Additionally, determined cryo-electron microscopy (cryo-EM) structure S protein complexed with mouse (mACE2) crystal RBD palm-civet (cvACE2). Several key for host range have been identified. These results suggest surveillance should be enhanced on broader-species prevent spillover expansion reservoir hosts a prolonged pandemic.

Language: Английский

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