scholarly journals Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs

2020 ◽  
Author(s):  
Camila Pontes ◽  
Victoria Ruiz-Serra ◽  
Rosalba Lepore ◽  
Alfonso Valencia
Keyword(s):  
Host Cell ◽  
Molecular Basis ◽  
Human Population ◽  
Cell Receptor ◽  
Protein Family ◽  
Spike Protein ◽  
Receptor Usage ◽  
Host Cell Receptor ◽  
Unsupervised Analysis ◽  
Conservation Patterns

AbstractThe recent emergence of the novel SARS-CoV-2 in China and its rapid spread in the human population has led to a public health crisis worldwide. Like in SARS-CoV, horseshoe bats currently represent the most likely candidate animal source for SARS-CoV-2. Yet, the specific mechanisms of cross-species transmission and adaptation to the human host remain unknown. Here we show that the unsupervised analysis of conservation patterns across the β-CoV spike protein family, using sequence information alone, can provide rich information on the molecular basis of the specificity of β-CoVs to different host cell receptors. More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). Furthermore, by integrating structural data, in silico mutagenesis and coevolution analysis we could elucidate the role of SDPs in mediating ACE2 binding across the Sarbecovirus lineage, either by engaging the receptor through direct intermolecular interactions or by affecting the local environment of the receptor binding motif. Finally, by the analysis of coevolving mutations across a paired MSA we were able to identify key intermolecular contacts occurring at the spike-ACE2 interface. These results show that effective mining of the evolutionary records held in the sequence of the spike protein family can help tracing the molecular mechanisms behind the evolution and host-receptors adaptation of circulating and future novel β-CoVs.SignificanceUnraveling the molecular basis for host cell receptor usage among β-CoVs is crucial to our understanding of cross-species transmission, adaptation and for molecular-guided epidemiological monitoring of potential outbreaks. In the present study, we survey the sequence conservation patterns of the β-CoV spike protein family to identify the evolutionary constraints shaping the functional specificity of the protein across the β-CoV lineage. We show that the unsupervised analysis of statistical patterns in a MSA of the spike protein family can help tracing the amino acid space encoding the specificity of β-CoVs to their cognate host cell receptors. We argue that the results obtained in this work can provide a framework for monitoring the evolution of SARS-CoV-2 specificity to the hACE2 receptor, as the virus continues spreading in the human population and differential virulence starts to arise.

scholarly journals Plasmodium P36 determines host cell receptor usage during sporozoite invasion

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Giulia Manzoni ◽  
Carine Marinach ◽  
Selma Topçu ◽  
Sylvie Briquet ◽  
Morgane Grand ◽  
...  
Keyword(s):  
Host Cell ◽  
Scavenger Receptor ◽  
Cell Receptor ◽  
Surface Proteins ◽  
Invasion Pathways ◽  
Functional Link ◽  
Scavenger Receptor Bi ◽  
Receptor Usage ◽  
Host Cell Receptor ◽  
Redundant Functions

Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, first infect the liver for an initial round of replication before the emergence of pathogenic blood stages. Sporozoites represent attractive targets for antimalarial preventive strategies, yet the mechanisms of parasite entry into hepatocytes remain poorly understood. Here we show that the two main species causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, rely on two distinct host cell surface proteins, CD81 and the Scavenger Receptor BI (SR-BI), respectively, to infect hepatocytes. By contrast, CD81 and SR-BI fulfil redundant functions during infection by the rodent parasite P. berghei. Genetic analysis of sporozoite factors reveals the 6-cysteine domain protein P36 as a major parasite determinant of host cell receptor usage. Our data provide molecular insights into the invasion pathways used by different malaria parasites to infect hepatocytes, and establish a functional link between a sporozoite putative ligand and host cell receptors.

scholarly journals Host-cell recognition through GRP78 is enhanced in the new UK variant of SARS-CoV-2, in silico 

2021 ◽  
Author(s):  
Abdo A Elfiky ◽  
Ibrahim M Ibrahim
Keyword(s):  
Host Cell ◽  
Cell Receptor ◽  
Spike Protein ◽  
Cell Recognition ◽  
Receptor Binding Domain ◽  
Host Cell Receptor ◽  
Mutant Variant ◽  
New Variant ◽  
The Uk ◽  
Host Cell Recognition

Abstract New SARS-CoV-2 variant VUI 202012/01 started in the UK and currently spreading in Europe and Australia during the last few days. The new variant bears about nine mutations in the spike protein (Δ69-70, Δ145, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H). The N501Y lies in the receptor-binding domain (RBD) of the spike and interacts with the host-cell receptor ACE2 responsible for viral recognition and entry. We tried to simulate the system of ACE2-SARS-CoV-2 spike RBD in the wildtype and mutated isoform of the RBD (N501Y). Additionally, the GRP78 association with the ACE2-SARS-CoV-2 spike RBD is modeled at the presence of this mutant variant of the viral spike.

scholarly journals Dynamical asymmetry exposes 2019-nCoV prefusion spike

2020 ◽  
Author(s):  
Susmita Roy
Keyword(s):  
Host Cell ◽  
Cell Receptor ◽  
Spike Protein ◽  
The Novel ◽  
Structural Topology ◽  
Dynamic Simulations ◽  
Asymmetric Structures ◽  
Host Cell Receptor ◽  
Model Hamiltonian ◽  
Novel Coronavirus

AbstractThe novel coronavirus (2019-nCoV) spike protein is a smart molecular machine that instigates the entry of coronavirus to the host cell causing the COVID-19 pandemic. In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. The study finds 2019-nCoV to adopt a unique strategy by undertaking a dynamic conformational asymmetry induced by a few unique inter-chain interactions. This results in two prevalent asymmetric structures of spike where one or two spike heads lifted up undergoing a dynamic transition likely to enhance rapid recognition of the host-cell receptor turning on its high-infectivity. The crucial interactions identified in this study are anticipated to potentially affect the efficacy of therapeutic targets.One Sentence SummaryInter-chain-interaction driven rapid symmetry breaking strategy adopted by the prefusion trimeric spike protein likely to make 2019-nCoV highly infective.

Understanding the Role of Corona Virus based on Current Scientific Evidence - A Review with Emerging Importance in Pandemic

2020 ◽  
Vol 15 (2) ◽  
pp. 89-103
Author(s):  
Suman K. Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Host Cell ◽  
Scientific Evidence ◽  
Antibody Therapy ◽  
Cell Receptor ◽  
Spike Protein ◽  
Virus Infectivity ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Antiviral Medications

: Coronavirus disease is a potentially deadly disease and of significant apprehension for global communal health because of its lethality. Vaccines and antiviral medications are still under trial to prevent or treat human coronavirus (HCoV) till date. The virus HCoV originated in 2003, SARS-CoV, which causes respiratory syndrome having distinctive pathogenesis and infections of the respiratory tract. A mechanism was projected for the evolution of SARS virus, and a handy association with bats was found. When this virus reaches the respective host system, the infection starts with spike protein binding to its complementary receptor of the host cell. The coronavirus spike protein’s association with its host cell receptor complement is crucial in deciding the virus infectivity, tissue tropism and species variety. Recent studies show that SARS Coronavirus 2 or COVID-19 requires protease to get into cells, offering a new therapeutic target. Distinctive attention and exertions should be given to defending or reducing transmission in vulnerable populaces, including those directly associated with caregiving and treatment and also aged one. Researchers are planning to develop a vaccine for COVID-19, and in this approach are also considered developing a vaccine that sensitizes our immune system preventing from this pandemic. The present review focuses on the role of S-spike protein in COVID-19, which helps the virus intruding the enzyme ACE2 (Angiotensin-Converting Enzyme 2). Passive antibody therapy is an additional alternative to use blood donors from hale and hearty people who have already recovered from COVID-19 and therapeutic advancement in handling the COVID-19 pandemic.

Role of bacteriophage SPP1 tail spike protein gp21 on host cell receptor binding and trigger of phage DNA ejection

2011 ◽  
Vol 83 (2) ◽  
pp. 289-303 ◽  
Author(s):  
Inês Vinga ◽  
Catarina Baptista ◽  
Isabelle Auzat ◽  
Isabelle Petipas ◽  
Rudi Lurz ◽  
...  
Keyword(s):  
Host Cell ◽  
Receptor Binding ◽  
Cell Receptor ◽  
Spike Protein ◽  
Host Cell Receptor ◽  
Dna Ejection ◽  
Phage Dna ◽  
Tail Spike

scholarly journals Author response: Plasmodium P36 determines host cell receptor usage during sporozoite invasion

2017 ◽  
Author(s):  
Giulia Manzoni ◽  
Carine Marinach ◽  
Selma Topçu ◽  
Sylvie Briquet ◽  
Morgane Grand ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Receptor ◽  
Author Response ◽  
Receptor Usage ◽  
Host Cell Receptor

scholarly journals COVID-19 Spike-host cell receptor GRP78 binding site prediction

2020 ◽  
Author(s):  
Ibrahim Ibrahim ◽  
Doaa Abdelmalek ◽  
Mohamed Elshahat ◽  
Abdo Elfiky
Keyword(s):  
Binding Site ◽  
Host Cell ◽  
Driving Force ◽  
Cell Receptor ◽  
Binding Domain ◽  
Cell Surface Receptor ◽  
Spike Protein ◽  
Cell Recognition ◽  
Host Cell Receptor ◽  
Host Cell Recognition

Abstract Coronaviruses have been circulating between animals and humans repeatedly. A novel human coronavirus, named COVID-19, has recently emerged in Hubei Province, China. Within the first two months, more than 2200 deaths have been confirmed, and there have been more than 79,000 hospitalized patients, mainly in China. Understanding the virus mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition. In this study, the COVID-19 corona viral spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The cyclic peptide Pep42 (CTVALPGGYVRVC) was reported earlier to be the docking platform of GRP78 in cancer cells. The COVID-19 spike protein is modeled using its counterpart, the SARS spike. Sequence and structural alignments show that four regions, in addition to its cyclic nature (the S-S bond), have sequence and physicochemical similarities to the cyclic Pep42. Protein-protein docking was performed to test the four regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor. We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These nine residues (region IV) of the spike can be used to develop therapeutics specific against COVID-19.

COVID 19 – Eye Issues

2020 ◽  
Vol 5 (Special) ◽  
Keyword(s):  
Host Cell ◽  
Target Cell ◽  
Cell Receptor ◽  
Human Tissues ◽  
Type Ii ◽  
Cell Infection ◽  
Host Cell Receptor ◽  
Infected Cells ◽  
Cellular Entry

The coronavirus illness (COVID-19) is caused by a new recombinant SARS-CoV (SARS-CoV) virus (SARS-CoV-2). Target cell infection by SARS-CoV is mediated by the prickly protein of the coronavirus and host cell receptor, enzyme 2 converting angiotensin (ACE2) [3]. Similarly, a recent study suggests that cellular entry by SARS-CoV-2 is dependent on both ACE2 as well as type II transmembrane axial protease (TMPRSS2) [4]. This means that detection of ACE2 and PRSS2 expression in human tissues can predict potential infected cells and their respective effects in COVID-19 patients [1].

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