scholarly journals Perspectives and potential approaches for targeting neuropilin 1 in SARS-CoV-2 infection

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Svetlana P. Chapoval ◽  
Achsah D. Keegan
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Virus Entry ◽  
Severe Disease ◽  
Spike Protein ◽  
Virus Infectivity ◽  
Human Response ◽  
Type B ◽  
Pathogenetic Mechanisms ◽  
Neuropilin 1 ◽  
Entry Receptor

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel type b coronavirus responsible for the COVID-19 pandemic. With over 224 million confirmed infections with this virus and more than 4.6 million people dead because of it, it is critically important to define the immunological processes occurring in the human response to this virus and pathogenetic mechanisms of its deadly manifestation. This perspective focuses on the contribution of the recently discovered interaction of SARS-CoV-2 Spike protein with neuropilin 1 (NRP1) receptor, NRP1 as a virus entry receptor for SARS-CoV-2, its role in different physiologic and pathologic conditions, and the potential to target the Spike–NRP1 interaction to combat virus infectivity and severe disease manifestations.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus-2 genome sequence variations relate to morbidity and mortality in Coronavirus Disease-19

2021 ◽  
Author(s):  
Poonam Mehta ◽  
Saumya Sarkar ◽  
Ujjala Ghoshal ◽  
Ankita Pandey ◽  
Ratender Singh ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Severe Disease ◽  
Gastrointestinal Symptoms ◽  
Spike Protein ◽  
Related Factors ◽  
Asymptomatic Group ◽  
Glycoprotein P ◽  
Sequence Variations ◽  
Genome Variations ◽  
Patient Subgroups

Outcome of infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) may depend on the host, virus or the host-virus interaction related factors. Complete SARS-CoV-2 genome was sequenced using Illumina and Nanopore platforms from naso-/oro-pharyngeal ri-bonucleic acid (RNA) specimens from COVID-19 patients of varying severity and outcomes, including patients with mild upper respiratory symptoms (n=35), severe disease admitted to intensive care with respiratory and gastrointestinal symptoms (n=21), fatal COVID-19 outcome (n=17) and asymptomatic (n=42). Of a number of genome variants observed, p.16L>L (Nsp1), p.39C>C (Nsp3), p.57Q>H (ORF3a), p.71Y>Y (Membrane glycoprotein), p.194S>L (Nucleocapsid protein) were observed in similar frequencies in different patient subgroups. However, seventeen other variants were observed only in symptomatic patients with severe and fatal COVID-19. Out of the latter, one was in the 5UTR (g.241C>T), eight were synonymous (p.14V>V and p.92L>L in Nsp1 protein, p.226D>D, p.253V>V, and p.305N>N in Nsp3, p.34G>G and p.79C>C in Nsp10 protein, p.789Y>Y in Spike protein), and eight were non-synonymous (p.106P>S, p.157V>F and p.159A>V in Nsp2, p.1197S>R and p.1198T>K in Nsp3, p.97A>V in RdRp, p.614D>G in Spike protein, p.13P>L in nucleocapsid). These were completely absent in the asymptomatic group. SARS-CoV-2 genome variations have a significant impact on COVID-19 presentation, severity and outcome.

scholarly journals In Silico Docking for Inhibition Neuropilin-1 (SARS-CoV-2 receptor) by Some Natural and Approved Drugs

2020 ◽  
Author(s):  
mohamed seadawy ◽  
Mohamed Shamel ◽  
Aya Ahmed ◽  
Abdel Rahman N. Zekri
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Severe Acute Respiratory Syndrome ◽  
Docking Study ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
In Silico Docking ◽  
Neuropilin 1 ◽  
Approved Drugs

Abstract Background: Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth and angiogenesis. Beside its role in cancer, NRP-1 is a reported entrance for several viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19). Methods: We made Insilco docking between the spike protein and Neuropilin-1 using Cluspro 2.0 software. Therefore, Neuropilin-1 becomes host factor for SARS-CoV-2 infection. Then by using molecular docking, we test nine compounds against Neuropilin-1 for its inhibition. Results: Our result revealed that NRP-1 receptor is considered as Therapeutic target for SARS-CoV2 treatment and screened with natural compounds and drugs (e.g. Carvacrol, Thymol, Amantadine, Daclatasvir, Ravidasvir, Remdesivir, Sofosbuvir, Hesperidine and Thymoquinone) by molecular docking study. Conclusion: These natural products and drugs may emerge as potential Neuropilin-1 inhibitor. However, additional exploration is predictable for the investigation of the essential use of the drugs and herbs containing these natural products and their in-vivo activity.

scholarly journals Metabotropic glutamate receptor subtype 2 is a receptor of SARS-CoV-2

2021 ◽  
Author(s):  
Zhigao Bu ◽  
Jinliang Wang ◽  
Guan Yang ◽  
Xinxin Wang ◽  
Zhiyuan Wen ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Spike Protein ◽  
Receptor Subtype ◽  
Angiotensin Converting Enzyme 2 ◽  
Metabotropic Glutamate ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Entry Receptor

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of novel coronavirus disease 2019 (COVID-19)1. SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as a cellular receptor and enters cells via clathrin-mediated endocytosis (CME)2-4. However, the key molecules involved in internalizing and facilitating CME for virus entry remain unknown. Here, we found metabotropic glutamate receptor subtype 2 (mGluR2) is a key entry receptor for SARS-CoV-2 infection. mGluR2 directly interacts with the SARS-CoV-2 spike protein. Knockdown of mGluR2 decreases endocytosis of SARS-CoV-2 but not cell binding. mGluR2 cooperates with ACE2 to facilitate SARS-CoV-2 entry through CME. Knockout of the mGluR2 gene in mice abolished SARS-CoV-2 infection in the nasal turbinates and significantly reduced viral infection in the lungs. Importantly, mGluR2 also is important for severe acute respiratory syndrome coronavirus spike protein and Middle East respiratory syndrome coronavirus spike protein mediated endocytosis. Our study provides important insights into SARS-CoV-2 infection and reveals an important target for the development of novel approaches to limit coronavirus infection.

scholarly journals Neuropilin-1 Assists SARS-CoV-2 Infection by Stimulating the Separation of Spike Protein Domains S1 and S2

2021 ◽  
Author(s):  
Zhenlu Li ◽  
Matthias Buck
Keyword(s):  
Molecular Dynamics ◽  
High Probability ◽  
Cell Surface Receptor ◽  
Spike Protein ◽  
Virus Infectivity ◽  
Topological Constraints ◽  
Exit Mechanism ◽  
Neuropilin 1 ◽  
Host Membrane ◽  
Surface Receptor

The cell surface receptor Neuropilin-1 (Nrp1) was recently identified as a host factor for SARS-CoV-2 entry. As the Spike protein of SARS-Cov-2 is cleaved into the S1 and the S2 domain by furin protease, Nrp1 binds to the newly created C-terminal RRAR amino acid sequence of the S1 domain. In this study, we model the association of a Nrp1 (a2-b1-b2) protein with the Spike protein computationally and analyze the topological constraints in the SARS-CoV-2 Spike protein for binding with Nrp1 and ACE2. Importantly, we study the exit mechanism of S2 from the S1 domain with the assistance of ACE2 as well as Nrp1 by molecular dynamics pulling simulations. In the presence of Nrp1, by binding the S1 more strongly to the host membrane, there is a high probability of S2 being pulled out, rather than S1 being stretched. Thus, Nrp1 binding could stimulate the exit of S2 from the S1 domain, which will likely increase virus infectivity as the liberated S2 domain mediates the fusion of virus and host membranes. Understanding of such a Nrp1-assisted viral infection opens the gate for the generation of protein-protein inhibitors, such as antibodies, which could attenuate the infection mechanism and protect certain cells in a future combination therapy.

scholarly journals Dynamics of Neutralizing Antibody Titers in the Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection

2020 ◽  
Author(s):  
Katharine H D Crawford ◽  
Adam S Dingens ◽  
Rachel Eguia ◽  
Caitlin R Wolf ◽  
Naomi Wilcox ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Time Frames ◽  
Initial Peak

Abstract Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

scholarly journals Transferrin receptor is another receptor for SARS-CoV-2 entry

2020 ◽  
Author(s):  
Xiaopeng Tang ◽  
Mengli Yang ◽  
Zilei Duan ◽  
Zhiyi Liao ◽  
Lei Liu ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Mouse Model ◽  
Angiotensin Converting Enzyme ◽  
Transferrin Receptor ◽  
Cell Membranes ◽  
Virus Entry ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

AbstractAngiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ~16.6 nM) shows promising anti-viral effects in mouse model. Collectively, this report indicates that TfR is another receptor for SARS-CoV-2 entry and a promising anti-COVID-19 target.

scholarly journals Transferrin receptor is another receptor for SARS-CoV-2 entry

2020 ◽  
Author(s):  
Ren Lai ◽  
Xiaopeng Tang ◽  
Mengli Yang ◽  
Zilei Duan ◽  
Zhiyi Liao ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Mouse Model ◽  
Angiotensin Converting Enzyme ◽  
Transferrin Receptor ◽  
Cell Membranes ◽  
Virus Entry ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Abstract Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ∼16.6 nM) shows promising anti-viral effects in mouse model. Collectively, this report indicates that TfR is another receptor for SARS-CoV-2 entry and a promising anti-COVID-19 target.

scholarly journals Immunological imprinting of the antibody response in COVID-19 patients

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Teresa Aydillo ◽  
Alexander Rombauts ◽  
Daniel Stadlbauer ◽  
Sadaf Aslam ◽  
Gabriela Abelenda-Alonso ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Humoral Immune Response ◽  
Nucleocapsid Protein ◽  
Spike Protein ◽  
Ongoing Research ◽  
Variable Regions ◽  
Humoral Immune ◽  
Human Coronaviruses

AbstractIn addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

scholarly journals CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Infection ◽  
2021 ◽  
Author(s):  
Jan-Moritz Doehn ◽  
Christoph Tabeling ◽  
Robert Biesen ◽  
Jacopo Saccomanno ◽  
Elena Madlung ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Disease Severity ◽  
Clinical Studies ◽  
Viral Infections ◽  
Severe Disease ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Expression Levels

AbstractCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

Sign in / Sign up

Export Citation Format

Share Document