The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike

Liu, Yu; Zhang, Ziding; Yang, Li; Lian, Xianyi; Xie, Yan; Shen, Li; Xin, Shuyu; Cao, Pengfei; Lu, Jianhong

doi:10.2139/ssrn.3570560

Cited by 68 publications

(89 citation statements)

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“…Thus, we finally used single-cell analysis of the syncytiotrophoblast, villous cytotrophoblast, and extravillous trophoblasts -the fetal component of the placenta -that confirmed the low-levels of expression of the canonical entry receptor ACE2 and TMPRSS2 genes (21,22). Conversely, we found that these cells express high-levels of DPP4 and CTSL, two potential mediators of SARS-Cov-2 host cell entry (27,30) that may contribute to the SARS-CoV-2 infection (17,25,26). It is essential to highlight that our scRNA-Seq analysis showed that the non-canonical DPP4 and CTSL entry genes (27,30) are highly co-expressed in syncytiotrophoblast, villous cytotrophoblast, and extravillous trophoblasts cells.…”

Section: Discussionmentioning

confidence: 53%

“…Conversely, we found that these cells express high-levels of DPP4 and CTSL, two potential mediators of SARS-Cov-2 host cell entry (27,30) that may contribute to the SARS-CoV-2 infection (17,25,26). It is essential to highlight that our scRNA-Seq analysis showed that the non-canonical DPP4 and CTSL entry genes (27,30) are highly co-expressed in syncytiotrophoblast, villous cytotrophoblast, and extravillous trophoblasts cells. The transcripts DAAM1 and PAICS, which are translated into proteins predicted as potentially interacting with SARS-CoV-2, were also highly coexpressed with DPP4 and CTSL.…”

Section: Discussionmentioning

confidence: 77%

“…Firstly, we characterized the expression of SARS-CoV-2/SARS-CoV entryassociated receptors and proteases genes, which revealed that DPP4 and CTSL are highly expressed in villous trophoblast cells during pregnancy. DPP4 has a high affinity to the SARS-CoV-2 spike receptor-binding domain, (27) and critical DPP4 residues share the SARS-CoV-2-S/DPP4 binding as found for MERS-CoV-S/DPP4 (27). In a pioneer study based on SARS-CoV cell entry mechanisms, Simmons et al (28) described a three-step method for host-virus membrane fusion, involving receptor-binding and induced conformational changes in S glycoprotein with subsequent CTSL proteolysis and activation of membrane fusion within endosomes.…”

Section: Discussionmentioning

confidence: 99%

“…SARS-CoV-2 cell entry mediators were selected for first screening using the human proteins already described in the COVID-19 Cell Atlas (https://www.covid19cellatlas.org/) and the literature (1,21,27,30). Next, we used gene expression data to generated a list of PPIs that potentially interact with human coronaviruses and the ZIKV from the Pathogen-Host Interactome Prediction using Structure Similarity (P-HIPSTer, http://phipster.org/) database (23) ( Supplementary Table 4 and 5, respectively).…”

Section: Placenta Proteins That Potentially Interact With Coronavirusmentioning

confidence: 99%

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Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Constantino

Cury

Nogueira

et al. 2020

Preprint

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The SARS-CoV-2 is the causative agent of the COVID-19 pandemic. The data available about COVID-19 during pregnancy have demonstrated placental infection; however, the intrauterine transmission of SARS-CoV-2 is still debated. Intriguingly, while canonical SARS-CoV-2 cell entry mediators are expressed at low levels in placental cells, the receptors for viruses that cause congenital infections such as the cytomegalovirus and Zika virus are highly expressed in these cells. Here we analyzed the transcriptional profile (microarray and single-cell RNA-Seq) of proteins potentially interacting with coronaviruses to identify non-canonical mediators of SARS-CoV-2 infection and replication in the placenta. We show that, despite low levels of the canonical cell entry mediators ACE2 and TMPRSS2, villous trophoblast cells co-express high levels of the potential non-canonical cell-entry mediators DPP4 and CTSL. We also found changes in the expression of DAAM1 and PAICS genes during pregnancy, which are translated into proteins also predicted to interact with coronaviruses proteins. These results provide new insight into the interaction between SARS-CoV-2 and host proteins that may act as non-canonical routes for SARS-CoV-2 infection and replication in the placenta cells.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Placenta Proteins That Potentially Interact With Coronavirusmentioning

confidence: 99%

See 2 more Smart Citations

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Constantino

Cury

Nogueira

et al. 2020

Preprint

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“…Identifying the host receptors which a virus can recognize is an important step in mechanistically explaining viral infection, and can offer insight in a virus' cellular tropism and factors influencing susceptibility. Despite the importance of determining precisely which entry receptors SARS-CoV-2 uses to infect human cells, there remains considerable uncertainty amid multiple claimed viral receptors with variable qualities of data behind them 9,[32][33][34][35] . We investigated one of the most prominent claims among these, that human BSG acts as an alternate receptor for the virus to interact with, which has been the topic of several studies, news and review articles, and a clinical trial 8,14,15,[36][37][38][39] .…”

Section: Discussionmentioning

confidence: 99%

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

Shilts

Wright

2020

Preprint

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The spike protein of SARS-CoV-2 is known to enable viral invasion into human cells through direct binding to host receptors including ACE2. An alternate entry receptor for the virus was recently proposed to be basigin/CD147. These early studies have already prompted a clinical trial and multiple published hypotheses of the role of this host receptor in viral infection and pathogenesis. We sought to independently characterize the basigin-spike protein interaction. After conducting several lines of experiments, we report that we are unable to find evidence supporting the role of basigin as a putative spike-binding receptor. Recombinant forms of both the entire ectodomain and S1 domain of the SARS-CoV-2 spike protein that directly bind ACE2 do not interact with basigin expressed on the surface of human cells. Using specialized assays tailored to detect receptor interactions as weak or weaker than the proposed basigin-spike binding, we report no evidence for direct binding of the viral spike to either of the two common isoforms of basigin. Given the pressing need for clarity on which targets of SARS-CoV-2 may lead to promising therapeutics, we present these findings to allow more informed decisions about the translational relevance of this putative mechanism in the race to understand and treat COVID-19.

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Managing diabetes in diabetic patients with COVID: where do we start from?

2021

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Aims COVID-19 has and still is sweeping away the national health systems worldwide. In this review, we sought to determine the evidence base proofs on the antidiabetic treatment capable to reduce the risk of COVID-19-related mortality. Methods We have performed a systematic search of published articles using PubMed, and EMBASE from March 2020 to March 31st, 2021. We excluded editorials, commentary, letters to the editor, reviews, and studies that did not have mortality as an outcome. For metformin and insulin only, we performed a meta-analysis using Cochrane RevMan 5.2. Results Among antidiabetic drugs, metformin was the only drug associated with a reduced risk of mortality. Conversely, insulin appears associated with an increased risk. The other classes of drugs were neutral. Conclusions The totality of articles reports retrospective data strongly affected by “channeling bias” so that most of the existing results on each class of drugs are driven by the phenotype of patients likely to receive that specific drug by prescription.

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The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike

Cited by 68 publications

References 0 publications

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

Managing diabetes in diabetic patients with COVID: where do we start from?

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