CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus (original) (raw)
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CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2
As the COVID-19 pandemic continues to spread, investigating the processes underlying the interactions between SARS-CoV-2 and its hosts is of high importance. Here, we report the identification of CD209L/L-SIGN and the related protein CD209/DC-SIGN as receptors capable of mediating SARS-CoV-2 entry into human cells. Immunofluorescence staining of human tissues revealed prominent expression of CD209L in the lung and kidney epithelium and endothelium. Multiple biochemical assays using a purified recombinant SARS-CoV-2 spike receptor binding domain (S-RBD) or S1 encompassing both NTB and RBD and ectopically expressed CD209L and CD209 revealed that CD209L and CD209 interact with S-RBD. CD209L contains two N-glycosylation sequons, at sites N92 and N361, but we determined that only site N92 is occupied. Removal of the N-glycosylation at this site enhances the binding of S-RBD with CD209L. CD209L also interacts with ACE2, suggesting a role for heterodimerization of CD209L and ACE2 in SARS-C...
The Mechanism of SARS-Co V-2 Entry into Human Cells and the Discovery of Multiple Viral Strains
2021
Coronaviruses, belonging to the Coronaviridae family, were first discovered in the 1960s having been characterized by the presence of distinct, protruding spike (S) proteins. This family of viruses is zoonotic, can be transferred from animals to humans, as demonstrated by the development of SARS-CoV-1 in 2002 from palm civets and MERS-CoV in 2012 from dromedary camels. The SAR-CoV-2 variety, the causative agent of the COVID-19 disease, emerged in Wuhan, China in December, 2019 from a currently unknown intermediate host. Like other coronaviruses, viral entry was facilitated by the binding of the S proteins to human ACE2 receptors. Although the symptoms, transmission, and morphology of SARS-CoV-2 virus were similar to SARS-CoV-1, the two types of coronaviruses had significant differences in their S proteins at the amino acid sequence level. The SARS-CoV-2 S protein amino acid sequence increases its affinity for ACE2 receptors, potentially explaining why it has been especially virulent. Additionally, two strains of SARS-CoV-2 have been discovered, indicating the possible need for two different types of CoV-2 vaccinations.
Expression, Glycosylation, and Modification of the Spike (S) Glycoprotein of SARS CoV
The spike (S) glycoprotein of coronaviruses is known to be essential in the binding of the virus to the host cell at the advent of the infection process. To study the maturation pathway of the S glycoprotein of the severe acute respiratory syndrome (SARS)coronavirus (CoV) within the host cell, a T7/vaccinia virus-based expression system coupled to immunoprecipitation with anti-S antibodies was used to test and analyze different forms of the S glycoprotein. The state of maturity of the S glycoprotein can be deduced from its sensitivity to hydrolysis by endoglycosidase H (EndoH) or N-glycosidase F (N-Gly F). A fully matured S glycoprotein will be modified with complex oligosaccharides which makes it resistant to cleavage by EndoH but not by N-Gly F. By exploiting this characteristic, it is then possible to determine which forms of the immunoprecipitated S protein are properly processed by the host cell. With this system, many different constructs of the S glycoprotein can be analyzed in parallel thus providing another method by which to study the functional domains of S involved in membrane fusion event that occurs during viral infection.
SARS COV-2: Exploring the Virus of the Century
https://www.ijrrjournal.com/IJRR\_Vol.8\_Issue.8\_Aug2021/IJRR-Abstract062.html, 2021
Coronaviruses comprise a large family of viruses that cause respiratory and intestinal infections in animals and humans. This recent outbreak of unusual respiratory disease plaguing the entire world has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the basis of phylogenetic analysis of related coronaviruses. Its transmission occurs mainly through airborn, fomite and other modes. Structurally, it is similar to other coronaviruses and has four major structural proteins; the spike surface glycoprotein (S), small envelope protein (E), matrix protein (M) and nucleocapsid protein (N). The M protein is most abundant and is responsible for intracellular formation of virus particles. S protein induces antibody generation and is involved in intracellular virus entry. Drug combinations are being tried on the basis of structural and genomic knowledge of the virus. Various researchers have found that the SARS CoV2 has many strains among which L type is most pathogenic and D614 type is most infective. All this information has been collected in this review to understand the virus behind this calamity in depth and to make it handy for the researchers to search literature related to SARS COV2.
Biochemical and Biophysical Research Communications, 2004
Studies of SARS coronavirus (SARS-CoV)-the causative agent of severe acute respiratory syndrome (SARS)-have been hampered by its high transmission rate and the pathogenicity of this virus. To permit analysis of the host range and entry mechanism of SARS-CoV, we incorporated the humanized SARS-CoV spike (S) glycoprotein into HIV particles to generate a highly infectious SARS-CoV pseudotyped virus. The infection on Vero E6-a permissive cell line to SARS-CoV-could be neutralized by sera from convalescent SARS patients, and the entry was a pH-dependent process. With these highly infectious SARS-CoV pseudotypes, several cell lines derived from various tissues were revealed as susceptible to SARS-CoV, which were highly corresponding to the expression pattern of virusÕs receptor angiotensin-converting enzyme 2 (ACE2). In addition, we also demonstrated angiotensin 1 converting enzyme (ACE)-the homologue of ACE2 could not function as a receptor for SARS-CoV.
Evolution of SARS-CoV-2 spike glycoprotein
2020
The spike glycoprotein (S) of SARS-CoV-2 mediates attachment of the virus to cell surface receptors and fusion between virus and cell membranes1. The receptor for SARS-CoV-2, like that for SARS-CoV, is the human cell-surface membrane protein ACE22–4. Membrane fusion activity, as for other class-1 fusion glycoproteins, requires S to be proteolytically cleaved into S1 and S2 that remain associated following cleavage4–7. SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host8,9. To better understand the transmission of SARS-CoV-2 we have determined the structure of its furin-cleaved S by cryoEM, which shows that cleavage at this polybasic amino-acid site increases the structural plasticity of the receptor binding region and facilitates the adoption of an open conformation that is required for it to bind to the ACE2 receptor. To investigate relationships between S proteins of SARS-CoV-2 and of the most closely related bat virus, RaTG138, we have determined and co...
2020
The widespread occurrence of SARS-CoV-2 has had a profound effect on society and a vaccine is currently being developed. Angiotensin-converting enzyme 2 (ACE2) is the primary host cell receptor that interacts with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Although pneumonia is the main symptom in severe cases of SARS-CoV-2 infection, the expression levels of ACE2 in the lung is low, suggesting the presence of another receptor for the spike protein. In order to identify the additional receptors for the spike protein, we screened a receptor for the SARS-CoV-2 spike protein from the lung cDNA library. We cloned L-SIGN as a specific receptor for the N-terminal domain (NTD) of the SARS-CoV-2 spike protein. The RBD of the spike protein did not bind to L-SIGN. In addition, not only L-SIGN but also DC-SIGN, a closely related C-type lectin receptor to L-SIGN, bound to the NTD of the SARS-CoV-2 spike protein. Importantly, cells expressing L-SIGN and DC-SIGN were both ...
2020
SummaryThe 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 tr...