CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2

Amraei, Razie; Yin, Wenqing; Napoleon, Marc Arthur; Suder, Ellen L.; Berrigan, Jacob; Zhao, Qing; Olejnik, Judith; Chandler, Kevin Brown; Xia, Chaoshuang; Feldman, Jared; Hauser, Blake M.; Caradonna, Timothy M.; Schmidt, Aaron; Gummuluru, Suryaram; Mühlberger, Elke; Chitalia, Vipul C.; Costello, Catherine E.; Rahimi, Nader

doi:10.1101/2020.06.22.165803

Cited by 152 publications

(209 citation statements)

References 54 publications

Supporting

Mentioning

200

Contrasting

Order By: Relevance

“…Therefore, we did not observe that these CLRs can function as alternative receptors to ACE2 in non-permissive cells such as T lymphocytes or HEK 293 (Supplementary information), as it has been recently suggested by Amraie et al (Amraie et al, 2020).…”

Section: Discussionmentioning

confidence: 51%

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Thépaut

Luczkowiak

Vivès

et al. 2020

Preprint

View full text Add to dashboard Cite

The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis.

show abstract

Section: Discussionmentioning

confidence: 51%

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Thépaut

Luczkowiak

Vivès

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Hence, the research community has an interest in studying the spike protein for drug and vaccine development. Amraie et al [ 9 ] recently reported that the C-type lectin receptors CD209L/L-SIGN and CD209/DSIGN serve as alternative receptors for SARS-CoV-2 entry into human cells. The C-type lectin domain could function as a calcium-dependent glycan-recognition domain.…”

Section: Introductionmentioning

confidence: 99%

The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter SemiSWEET

Thomas

2020

PAI

123

115

View full text Add to dashboard Cite

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the disease COVID-19 that has decimated the health and economy of our planet. The virus causes the disease not only in people but also in companion and wild animals. People with diabetes are at risk of the disease. As yet we do not know why the virus has been highly successful in causing the pandemic within 3 months of its first report. The structural proteins of SARS include membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N), and the spike protein (S). Methods: The structure and function of the most abundant structural protein of SARS-CoV-2, the membrane (M) glycoprotein, is not fully understood. Using in silico analyses we determined the structure and potential function of the M protein. Results: The M protein of SARS-CoV-2 is 98.6% similar to the M protein of bat SARS-CoV, maintains 98.2% homology with pangolin SARS-CoV, and has 90% homology with the M protein of SARS-CoV; whereas, the similarity is only 38% with the M protein of MERS-CoV. In silico analyses showed that the M protein of SARS-CoV-2 has a triple helix bundle, forms a single 3-transmembrane domain, and is homologous to the prokaryotic sugar transport protein SemiSWEET. SemiSWEETs are related to the PQ-loop family whose members function as cargo receptors in vesicle transport, mediate movement of basic amino acids across lysosomal membranes, and are also involved in phospholipase flippase function. Conclusions: The advantage and role of the M protein having a sugar transporter-like structure is not clearly understood. The M protein of SARS-CoV-2 interacts with S, E, and N protein. The S protein of the virus is glycosylated. It could be hypothesized that the sugar transporter-like structure of the M protein influences glycosylation of the S protein. Endocytosis is critical for the internalization and maturation of RNA viruses, including SARS-CoV-2. Sucrose is involved in endosome and lysosome maturation and may also induce autophagy, pathways that help in the entry of the virus. Overall, it could be hypothesized that the SemiSWEET sugar transporter-like structure of the M protein may be involved in multiple functions that may aid in the rapid proliferation, replication, and immune evasion of the SARS-CoV-2 virus. Biological experiments would validate the presence and function of the SemiSWEET sugar transporter.

show abstract

“…DC-SIGN (CD209) and L-SIGN (CD209L), immunoglobulin-like cell adhesion molecule superfamily receptors, and Neuropilin-1 can be alternative receptors that SARS-CoV-2 binds to in the vascular and nervous systems, respectively. L-SIGN serves as a receptor and attachment factor for several viruses, including SARS-CoV, HCoV-229E, HIV, Ebola, and other enveloped viruses [ 13 , 21–23 ]. DC-SIGN and L-SIGN can bind to the RBD of S proteins, facilitating SARS-CoV-2 entry.…”

Section: Introductionmentioning

confidence: 99%

“…DC-SIGN and L-SIGN can bind to the RBD of S proteins, facilitating SARS-CoV-2 entry. However, the binding affinity of ACE2 to RBD is higher than that of DC-SIGN and L-SIGN [ 13 ]. SARS-CoV-2 can also utilize endosomal protease cathepsin B and L during entry via endocytosis [ 11 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Robust and persistent SARS-CoV-2 infection in the human intestinal brush border expressing cells

Lee

Yoon

Myoung

et al. 2020

Emerging Microbes & Infections

View full text Add to dashboard Cite

Studies on patients with the coronavirus disease-2019 (COVID-19) have implicated that the gastrointestinal (GI) tract is a major site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We established a human GI tract cell line model highly permissive to SARS-CoV-2. These cells, C2BBe1 intestinal cells with a brush border having high levels of transmembrane serine protease 2 (TMPRSS2), showed robust viral propagation, and could be persistently infected with SARS-CoV-2, supporting the clinical observations of persistent GI infection in COVID-19 patients. Ectopic expression of viral receptors revealed that the levels of angiotensin-converting enzyme 2 (ACE2) expression confer permissiveness to SARS-CoV-2 infection, and TMPRSS2 greatly facilitates ACE2-mediated SARS-CoV-2 dissemination. Interestingly, ACE2 but not TMPRSS2 expression was significantly promoted by enterocytic differentiation, suggesting that the state of enterocytic differentiation may serve as a determining factor for viral propagation. Thus, our study sheds light on the pathogenesis of SARS-CoV-2 in the GI tract.

show abstract

CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2

Cited by 152 publications

References 54 publications

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter SemiSWEET

Robust and persistent SARS-CoV-2 infection in the human intestinal brush border expressing cells

Contact Info

Product

Resources

About