Receptor recognition and cross-species infections of SARS coronavirus.
Ontology highlight
ABSTRACT:
SUBMITTER: Li F
PROVIDER: S-EPMC3840050 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection
2010-06-05 | E-GEOD-546 | biostudies-arrayexpress
Project description:The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2-related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.
| S-EPMC7817217 | biostudies-literature
Project description:The sequential determination of crystal structures of the SARS coronavirus spike receptor-binding domain (RBD) in complex with its cellular receptor or neutralizing antibody opened a door for the design and development of antiviral competitive inhibitors. Based on those complex structures, we conduct computational characterization and design of RBD-mediated receptor recognition and antibody neutralization. The comparisons between computational predictions and experimental evidences validate our structural bioinformatics protocols. And the calculations predict a number of single substitutions on RBD, receptor or antibody that could remarkably elevate the binding affinities of those complexes. It is reasonable to anticipate our structure-based computation-derived hypotheses could be informative to the future biochemical and immunological tests.
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Project description:Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV's capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV.IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.
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Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection Keywords: repeat sample
2003-10-19 | GSE546 | GEO
Project description:A variety of coronaviruses (CoVs) have infected humans and caused mild to severe respiratory diseases that could result in mortality. The human CoVs (HCoVs) belong to the genera of α- and β-CoVs that originate in rodents and bats and are transmitted to humans via zoonotic contacts. The binding of viral spike proteins to the host cell receptors is essential for mediating fusion of viral and host cell membranes to cause infection. The SARS-CoV-2 originated in bats (RaTG13 SARS-CoV) and is transmitted to humans via pangolins. The presence of 'PRRA' sequence motif in SARS-CoV-2 spike proteins from human, dog, cat, mink, tiger and lion suggests a common viral entry mechanism into host cells. In this review, we discuss structural features of HCoV spike proteins and recognition of host protein and carbohydrate receptors.
| S-EPMC7604128 | biostudies-literature
Project description:We report that cells refractory to canine coronavirus (CCV) and feline infectious peritonitis virus (FIPV) became susceptible when transfected with a chimeric aminopeptidase-N (APN) cDNA containing a canine domain between residues 643 and 841. This finding shows that APN recognition by these viruses is species related and associated with this C-terminal domain. The human/canine APN chimera was also able to confer susceptibility to the porcine transmissible gastroenteritis virus (TGEV), whereas its human/porcine homolog failed to confer susceptibility to CCV and FIPV. A good correlation was observed between the capacity of CCV, FIPV, and TGEV to recognize the different interspecies APN chimeras and their ability to infect cells derived from the relevant species. As an exception, TGEV was found to use a human/bovine APN chimera as a receptor although itself unable to replicate in bovine cells.
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Project description:The emerging disease SARS is caused by a novel coronavirus that encodes several unusual RNA-processing enzymes, including non-structural protein 15 (Nsp15), a hexameric endoribonuclease that preferentially cleaves at uridine residues. How Nsp15 recognizes and cleaves RNA is not well understood and is the subject of this study. Based on the analysis of RNA products separated by denaturing gel electrophoresis, Nsp15 has been reported to cleave both 5' and 3' of the uridine. We used several RNAs, including some with nucleotide analogs, and mass spectrometry to determine that Nsp15 cleaves only 3' of the recognition uridylate, with some cleavage 3' of cytidylate. A highly conserved RNA structure in the 3' non-translated region of the SARS virus was cleaved preferentially at one of the unpaired uridylate bases, demonstrating that both RNA structure and base-pairing can affect cleavage by Nsp15. Several modified RNAs that are not cleaved by Nsp15 can bind Nsp15 as competitive inhibitors. The RNA binding affinity of Nsp15 increased with the content of uridylate in substrate RNA and the co-factor Mn(2+). The hexameric form of Nsp15 was found to bind RNA in solution. A two-dimensional crystal of Nsp15 in complex with RNA showed that at least two RNA molecules could be bound per hexamer. Furthermore, an 8.3 A structure of Nsp15 was developed using cyroelectron microscopy, allowing us to generate a model of the Nsp15-RNA complex.
| S-EPMC7118729 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that among the genomes analyzed, two sequence regions in the N-terminal domain "MESEFR" and "SYLTPG" are specific to human SARS CoV-2. In the receptor-binding domain, two sequence regions "VGGNY" and "EIYQAGSTPCNGV" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources, and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV-2 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression toward becoming human SARS CoV-2.
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Project description:Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the Deltacoronavirus genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the Alphacoronavirus genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood.
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