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

Yan, Huan; Wang, Xiangxi; Xiong, Qing; Cao, Lei; Ma, Chengbao; Liu, Chen; Si, Junyu; Liu, Peng; Gu, Mengxue; Wang, Chunli; Shi, Lei; Tong, Fei; Huang, Meiling; zhao, chufeng; Shen, Chao; Zhao, Huabin; Lan, Ke; Li, Jing

doi:10.21203/rs.3.rs-1292418/v1

Cited by 3 publications

(11 citation statements)

References 32 publications

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“…However, we did find evidence of selection in residues 321 and 326 in both bats and non-bat mammals (figure 1 c ; electronic supplementary material, table S3, MEME, p < 0.05), as well as selection in bats in residue 322 (figure 1 c ; electronic supplementary material, table S3, MEME, p < 0.05); these three residues contact HCoV-NL63 but not SARS-CoV or SARS-CoV-2. This finding contrasts with the findings of a smaller dataset of bats mostly from Europe, Asia and Africa which found no evidence of selection due to HCoV-NL63 [9] and may result from our greater power to detect signal or signal originating from bats in different regions than previously tested [31,32]. Recent evidence suggests that some MERS-CoV-related viruses use ACE2 as their host receptor [31], so this signal could be driven by coronaviruses from outside the SARS-related clade.…”

Section: Resultscontrasting

confidence: 95%

Exceptional diversity and selection pressure on coronavirus host receptors in bats compared to other mammals

2022

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Pandemics originating from non-human animals highlight the need to understand how natural hosts have evolved in response to emerging human pathogens and which groups may be susceptible to infection and/or potential reservoirs to mitigate public health and conservation concerns. Multiple zoonotic coronaviruses, such as severe acute respiratory syndrome-associated coronavirus (SARS-CoV), SARS-CoV-2 and Middle Eastern respiratory syndrome-associated coronavirus (MERS-CoV), are hypothesized to have evolved in bats. We investigate angiotensin-converting enzyme 2 (ACE2), the host protein bound by SARS-CoV and SARS-CoV-2, and dipeptidyl-peptidase 4 (DPP4 or CD26), the host protein bound by MERS-CoV, in the largest bat datasets to date. Both the ACE2 and DPP4 genes are under strong selection pressure in bats, more so than in other mammals, and in residues that contact viruses. Additionally, mammalian groups vary in their similarity to humans in residues that contact SARS-CoV, SARS-CoV-2 and MERS-CoV, and increased similarity to humans in binding residues is broadly predictive of susceptibility to SARS-CoV-2. This work augments our understanding of the relationship between coronaviruses and mammals, particularly bats, provides taxonomically diverse data for studies of how host proteins are bound by coronaviruses and can inform surveillance, conservation and public health efforts.

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Section: Resultscontrasting

confidence: 95%

Exceptional diversity and selection pressure on coronavirus host receptors in bats compared to other mammals

2022

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“…The first two genera can infect mammals (bats and humans), whereas the latter primarily infect birds and, sometimes, mammals. Most coronaviruses that infect humans are believed to have originated in bats—the key mammalian coronavirus reservoir ( 1 , 2 ). Bat-CoVs have received particular attention since several recently seen CoVs have been associated with unexpected disease outbreaks in the present century, causing high fatality rates and significant economic impact.…”

Section: Introductionmentioning

confidence: 99%

“…Bat-CoVs have received particular attention since several recently seen CoVs have been associated with unexpected disease outbreaks in the present century, causing high fatality rates and significant economic impact. Three such viruses suggested to be transmitted from bats to humans include Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and the latest Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) ( 2 , 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…Nonetheless, the cell entry receptor for NeoCoV is unspecified so far ( 11 ). NeoCoV and closely related PDF-2180-CoV can use certain forms of bat angiotensin-converting enzyme 2 (ACE2) and human ACE2 for cell entry, according to the latest research in preprint ( 2 ). The NeoCoV virus utilizes its S1 subunit at carboxyl-terminal domains (S1-CTD) of spike protein to bind with ACE2 with great affinity and species specificity.…”

Section: Introductionmentioning

confidence: 99%

“…The NeoCoV virus utilizes its S1 subunit at carboxyl-terminal domains (S1-CTD) of spike protein to bind with ACE2 with great affinity and species specificity. Besides, a molecular determinate (Asp338) was uncovered at the binding interface of the virus that prevent NeoCoV entry via human ACE2 ( 2 ). Researchers found that T510F mutation at the receptor-binding motif leads to increase the efficiency of NeoCoV to infect the human cells expressing ACE2 receptor ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Exploring whole proteome to contrive multi-epitope-based vaccine for NeoCoV: An immunoinformtics and in-silico approach

et al. 2022

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Neo-Coronavirus (NeoCoV) is a novel Betacoronavirus (β-CoVs or Beta-CoVs) discovered in bat specimens in South Africa during 2011. The viral sequence is highly similar to Middle East Respiratory Syndrome, particularly that of structural proteins. Thus, scientists have emphasized the threat posed by NeoCoV associated with human angiotensin-converting enzyme 2 (ACE2) usage, which could lead to a high death rate and faster transmission rate in humans. The development of a NeoCoV vaccine could provide a promising option for the future control of the virus in case of human infection. In silico predictions can decrease the number of experiments required, making the immunoinformatics approaches cost-effective and convenient. Herein, with the aid of immunoinformatics and reverse vaccinology, we aimed to formulate a multi-epitope vaccine that may be used to prevent and treat NeoCoV infection. Based on the NeoCoV proteins, B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were shortlisted. Four vaccines (Neo-1–4) were devised by fusing shortlisted epitopes with appropriate adjuvants and linkers. The secondary and three-dimensional structures of final vaccines were then predicted. The binding interactions of these potential vaccines with toll-like immune receptors (TLR-2, TLR-3, and TLR-4) and major histocompatibility complex molecules (MHC-I and II) reveal that they properly fit into the receptors’ binding domains. Besides, Neo-1 and Neo-4 vaccines exhibited better docking energies of -101.08 kcal/mol and -114.47 kcal/mol, respectively, with TLR-3 as compared to other vaccine constructs. The constructed vaccines are highly antigenic, non-allergenic, soluble, non-toxic, and topologically assessable with good physiochemical characteristics. Codon optimization and in-silico cloning confirmed efficient expression of the designed vaccines in Escherichia coli strain K12. In-silico immune simulation indicated that Neo-1 and Neo-4 vaccines could induce a strong immune response against NeoCoV. Lastly, the binding stability and strong binding affinity of Neo-1 and Neo-4 with TLR-3 receptor were validated using molecular dynamics simulations and free energy calculations (Molecular Mechanics/Generalized Born Surface Area method). The final vaccines require experimental validation to establish their safety and effectiveness in preventing NeoCoV infections.

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Identification and Genetic Characterization of MERS-Related Coronavirus Isolated from Nathusius’ Pipistrelle (Pipistrellus nathusii) near Zvenigorod (Moscow Region, Russia)

Speranskaya

Artyushin

Samoilov

et al. 2023

IJERPH

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Being diverse and widely distributed globally, bats are a known reservoir of a series of emerging zoonotic viruses. We studied fecal viromes of twenty-six bats captured in 2015 in the Moscow Region and found 13 of 26 (50%) samples to be coronavirus positive. Of P. nathusii (the Nathusius’ pipistrelle), 3 of 6 samples were carriers of a novel MERS-related betacoronavirus. We sequenced and assembled the complete genome of this betacoronavirus and named it MOW-BatCoV strain 15-22. Whole genome phylogenetic analysis suggests that MOW-BatCoV/15-22 falls into a distinct subclade closely related to human and camel MERS-CoV. Unexpectedly, the phylogenetic analysis of the novel MOW-BatCoV/15-22 spike gene showed the closest similarity to CoVs from Erinaceus europaeus (European hedgehog). We suppose MOW-BatCoV could have arisen as a result of recombination between ancestral viruses of bats and hedgehogs. Molecular docking analysis of MOW-BatCoV/15-22 spike glycoprotein binding to DPP4 receptors of different mammals predicted the highest binding ability with DPP4 of the Myotis brandtii bat (docking score −320.15) and the E. europaeus (docking score –294.51). Hedgehogs are widely kept as pets and are commonly found in areas of human habitation. As this novel bat-CoV is likely capable of infecting hedgehogs, we suggest hedgehogs can act as intermediate hosts between bats and humans for other bat-CoVs.

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

Cited by 3 publications

References 32 publications

Exceptional diversity and selection pressure on coronavirus host receptors in bats compared to other mammals

Exceptional diversity and selection pressure on coronavirus host receptors in bats compared to other mammals

Exploring whole proteome to contrive multi-epitope-based vaccine for NeoCoV: An immunoinformtics and in-silico approach

Identification and Genetic Characterization of MERS-Related Coronavirus Isolated from Nathusius’ Pipistrelle (Pipistrellus nathusii) near Zvenigorod (Moscow Region, Russia)

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