Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond

Lu, Guangwen; Wang, Qihui; Gao, George F.

doi:10.1016/j.tim.2015.06.003

Cited by 580 publications

(625 citation statements)

References 120 publications

(173 reference statements)

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“…The envelope spike (S) protein mediates receptor binding and membrane fusion 24 and is crucial for determining host tropism and transmission capacity. 25,26 Generally, the spike protein of coronaviruses is functionally divided into the S1 domain (especially positions 318-510 of SARS-CoV), responsible for receptor binding, and the S2 domain, responsible for cell membrane fusion. 27 The 2019-nCoV S2 protein showed around 93% sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21-much higher than that of the S1 domain, which had only around 68% identity with these bat-derived viruses.…”

Section: -Ncov Consensusmentioning

confidence: 99%

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

et al. 2020

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Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. MethodsWe did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus.Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues.Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensinconverting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation.

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Section: -Ncov Consensusmentioning

confidence: 99%

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

et al. 2020

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“…It is generally considered that transmission is mediated primarily by mutations with increased affinity to human receptors (14); alternatively, it has been proposed a "super-spreader" has emerged (15). However; in-depth interviews with some of the family members, indicated that the probable risk factors were exposure of the index case to a high dose of corona virus and delayed diagnosis due to denial by family members; these factors were exacerbated by improper risk communication and inadequate compliance with IPC measures in the hospitals.…”

Section: Discussionmentioning

confidence: 99%

An outbreak of Middle East Respiratory Syndrome (MERS) due to coronavirus in Al-Ahssa Region, Saudi Arabia, 2015

Bushra¹,

Abdalla²,

Arbash³

et al. 2016

East Mediterr Health J

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Between 19 April and 23 June 2015, 52 laboratory-confirmed cases of Middle East RespiratorySyndrome due to coronavirus (MERS) were reported from Al-Ahssa region, eastern Saudi Arabia. The first seven cases occurred in one family; these were followed by 45 cases in three public hospitals. The objectives of this investigation were to describe the epidemiological characteristic of the cluster and identify potential risk factors and control measures to be instituted to prevent further occurrence of MERS. We obtained the medical records of all confirmed cases, interviewed the members of the affected household and reviewed the actions taken by the health authorities. All the cases were connected. The index case was a 62-year-old man with a history of close contact with dromedary camels; three of the seven infected family members and 18 people in hospitals died (case-fatality rate, 40.4%). The median incubation period was about 6 days. The cluster of cases appeared to be due to high exposure to MERS, delayed diagnosis, inadequate risk communication and inadequate compliance of hospital health workers and visitors with infection prevention and control measures.

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“…SARS-CoV and MERS-CoV exploited mechanistically different approaches to overcome the human species barrier, but these two viruses have a lot in common (Lu et al 2015). Here, we aim to identify the vulnerable regions in the proteomes of coronaviruses that neither SARS-CoV nor MERS-CoV nor their contemporary and forthcoming relatives can proliferate without, and address how to mobilize a defense against the present and future coronaviruses by targeting these regions.…”

Section: Introductionmentioning

confidence: 99%

Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

Rahaman

Siltberg-Liberles

2016

Genome Biology and Evolution

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Within the last 15 years, two related coronaviruses (Severe Acute Respiratory Syndrome [SARS]-CoV and Middle East Respiratory Syndrome [MERS]-CoV) expanded their host range to include humans, with increased virulence in their new host. Coronaviruses were recently found to have little intrinsic disorder compared with many other virus families. Because intrinsically disordered regions have been proposed to be important for rewiring interactions between virus and host, we investigated the conservation of intrinsic disorder and secondary structure in coronaviruses in an evolutionary context. We found that regions of intrinsic disorder are rarely conserved among different coronavirus protein families, with the primary exception of the nucleocapsid. Also, secondary structure predictions are only conserved across 50–80% of sites for most protein families, with the implication that 20–50% of sites do not have conserved secondary structure prediction. Furthermore, nonconserved structure sites are significantly less constrained in sequence divergence than either sites conserved in the secondary structure or sites conserved in loop. Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. The identified sequence motif is found within the nonstructural protein (NSP) 12 and constitutes an antiviral target potentially effective against the present day and future coronaviruses. On shorter evolutionary timescales, the SARS and MERS clades have more sequence motifs fulfilling the criteria applied. Interestingly, many motifs map to NSP12 making this a prime target for coronavirus antivirals.

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Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond

Cited by 580 publications

References 120 publications

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

An outbreak of Middle East Respiratory Syndrome (MERS) due to coronavirus in Al-Ahssa Region, Saudi Arabia, 2015

Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

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