scholarly journals Deciphering the O-Glycosylation of HKU1 Spike Protein With the Dual-Functional Hydrophilic Interaction Chromatography Materials

2021 ◽  
Vol 9 ◽  
Author(s):  
Yun Cui ◽  
Xuefang Dong ◽  
Xiaofei Zhang ◽  
Cheng Chen ◽  
Dongmei Fu ◽  
...  
Keyword(s):  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
Biological Functions ◽  
Hydrophilic Interaction ◽  
Protein Surface ◽  
Enrichment Method ◽  
Dual Functional ◽  
Glycosylation Sites ◽  
Comprehensive Study

HKU1 is a human beta coronavirus and infects host cells via highly glycosylated spike protein (S). The N-glycosylation of HKU1 S has been reported. However, little is known about its O-glycosylation, which hinders the in-depth understanding of its biological functions. Herein, a comprehensive study of O-glycosylation of HKU1 S was carried out based on dual-functional histidine-bonded silica (HBS) materials. The enrichment method for O-glycopeptides with HBS was developed and validated using standard proteins. The application of the developed method to the HKU1 S1 subunit resulted in 46 novel O-glycosylation sites, among which 55.6% were predicted to be exposed on the outer protein surface. Moreover, the O-linked glycans and their abundance on each HKU1 S1 site were analyzed. The obtained O-glycosylation dataset will provide valuable insights into the structure of HKU1 S.

scholarly journals Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface

2020 ◽  
Author(s):  
Micholas Smith ◽  
Jeremy C. Smith
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
The Novel ◽  
S Protein ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Ranked List

The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.<br>

scholarly journals Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface

2020 ◽  
Author(s):  
Micholas Smith ◽  
Jeremy C. Smith
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
The Novel ◽  
S Protein ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Ranked List

The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.<br>

scholarly journals SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
S. D. Lam ◽  
N. Bordin ◽  
V. P. Waman ◽  
H. M. Scholes ◽  
P. Ashford ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Protein ◽  
Vertebrate Species ◽  
Animal Management ◽  
Structural Interactions ◽  
Viral Host Range ◽  
Key Residues

Abstract SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.

scholarly journals The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2

2020 ◽  
Author(s):  
Erik Procko
Keyword(s):  
Receptor Binding ◽  
Binding Sites ◽  
Protein S ◽  
Public Health Emergency ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Sars Coronavirus ◽  
Molecular Events ◽  
Proteins And Peptides

SUMMARYThe rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S binds ACE2 on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.

SARS-CoV-2 proteins: Are they useful as targets for COVID-19 drugs and vaccines?

2021 ◽  
Vol 21 ◽  
Author(s):  
Mohammed Elimam Ahamed Mohammed
Keyword(s):  
Lipid Bilayer ◽  
Drug Targets ◽  
Protein S ◽  
Bilayer Membrane ◽  
Viral Envelope ◽  
Host Cells ◽  
Spike Protein ◽  
Structural Proteins ◽  
Accessory Proteins ◽  
N Protein

: The proteins of coronavirus are classified to nonstructural, structural, and accessory. There are 16 nonstructural viral proteins beside their precursors (1a and 1ab polyproteins). The nonstructural proteins are named as nsp1 to nsp16 and they act as enzymes, coenzymes, and binding proteins to facilitate the replication, transcription, and translation of the virus. The structural proteins are bound to the RNA in the nucleocapsid (N- protein) or to the lipid bilayer membrane of the viral envelope. The lipid bilayer proteins include the membrane protein (M), envelope protein (E), and spike protein (S). Beside their role as structural proteins, they are essential for the host cells binding and invasion. The SARS-CoV-2 contains six accessory proteins which participates in the viral replication, assembly and virus- host interactions. The SARS-CoV-2 accessory proteins are orf3a, orf6, orf7a, orf7b, orf8, and orf10. The functions of the SARS-CoV-2 are not well known, while the functions of their corresponding proteins in SARS-CoV are either well known or poorly studied. Recently, the Oxford University and Pfizer and BioNTech made SARS-CoV-2 vaccines through targeting the spike protein gene. The US Food and Drug Administration (FDA) and the health authorities of the United Kingdom approved and started vaccination using the Pfizer and BioNTech mRNA vaccine. Also, The FDA of USA approved the treatment of COVID-19 using two monoclonal antibodies produced by Regeneron pharmaceuticals to target the spike protein. The SARS-CoV-2 proteins can be used for the diagnosis, as drug targets and in vaccination trials for COVID-19. For future COVID-19 research, more efforts should be done to elaborate the functions and structure of the SARS-CoV-2 proteins so as to use them as targets for COVID-19 drug and vaccines. Special attention should be drawn to extensive research on the SARS-CoV-2 nsp3, orf8, and orf10.

scholarly journals Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface

2020 ◽  
Author(s):  
Micholas Smith ◽  
Jeremy C. Smith
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
The Novel ◽  
S Protein ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Ranked List

The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.<br>

scholarly journals Contemplating SARS-CoV-2 infectivity with respect to ABO blood groups

2021 ◽  
Vol 5 (2) ◽  
pp. 082-086
Author(s):  
ul-Ain Amjad Qurat- ◽  
Saeed Umar ◽  
Piracha Zahra Zahid ◽  
Kanwal Kashmala ◽  
Munir Madiha ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Environmental Factors ◽  
Pregnant Women ◽  
Blood Group ◽  
Protein S ◽  
Blood Groups ◽  
Host Cells ◽  
Spike Protein ◽  
Blood Group A ◽  
Group A

COVID-19 is a disease that is caused by SARS-CoV-2 and very speedily spreading all over the world. The blood group’s effect on COVID-19 is not clear. The main aim of this article is to determine the relationship between sensitivity of COVID-19 and ABO blood group. For this study we have observed that the individuals with blood group A are at higher risk of getting COVID-19 because they contain the higher concentration of Angiotensin-converting enzyme-2 that provide the site to virus for entry. But in other blood groups the natural Anti A antibodies block the interaction between host receptor and virus and disturb their interaction. Certain studies show that the infectivity and mortality rate in covid patients is not affected by AB blood group system. But according to research, increased ventilator usage, ICU stay was observed in critically ill patients with AB blood group than of other blood groups. O blood group has proved to be protective against SARS-CoV-2 due to the presence of both anti-A and anti-B antibodies as they prevent the binding of the spike protein S of the virus with the ACE2 receptors which are present on the surface of cells. Moreover, furin also plays a major role in penetration of virus in the host cells. Furin is required for the activation of the spike protein S of the virus and due to the low efficiency of furin cleavage in blood group O it is protected from SARS-CoV-2 and other chronic diseases. Mortality rate of covid 19 depends upon the environmental factors, number of people living in the area and also some economic factors. The different strains of COVID-19 effect the different people differently and as the time passes the strain of COVID-19 has changed and thus according to this the mortality rate of different provinces and areas varies due to environmental factors. Pregnant women have no any kind of transportation of covid to their fetuses but mostly patients of blood group A are being affected by COVID-19 and hence their fetuses are somehow effected. And those pregnant women having blood group O does not have any risk of COVID-19 of severe stages.

scholarly journals SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals

2020 ◽  
Author(s):  
SD Lam ◽  
N Bordin ◽  
VP Waman ◽  
HM Scholes ◽  
P Ashford ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Protein ◽  
Vertebrate Species ◽  
Animal Management ◽  
Structural Interactions ◽  
Viral Host Range ◽  
Key Residues

AbstractSARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.

scholarly journals Sea Urchin Pigments as Potential Therapeutic Agents Against the Spike Protein of SARS-CoV-2 Based on in Silico Analysis

2020 ◽  
Author(s):  
Elena Susana Barbieri ◽  
Tamara Rubilar ◽  
Ayelén Gázquez ◽  
Marisa Avaro ◽  
Erina Noé Seiler ◽  
...  
Keyword(s):  
Sea Urchin ◽  
In Silico ◽  
In Silico Analysis ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
Therapeutic Drug ◽  
The Novel ◽  
Novel Coronavirus ◽  
Silico Analysis

Several studies have been published regarding the interaction between the spike protein of the novel coronavirus SARS-CoV-2 and ACE2 receptor in the host cells. In the presente work, we evaluated the in silico properties of two sea urchin pigments, Echinochrome A (EchA) and Spinochromes (SpinA) against the Spike protein (S) towards finding a potential therapeutic drug against the disease caused by the novel coronavirus (COVID-19). The best ensemble docking pose of EchaA and SpinA showed a binding affinity of -5.9 and -6.7 kcal mol-1, respectively. The linked aminoacids (T505, G496 and Y449 for EchA and Y449, Q493 and G496 for SpinA) are in positions involved in ACE2 binding in both RBDs frim SARS-CoV and SARS-CoV-2 suggesting that EchA and SpinA may interact with Spike proteins drom both viruses. The results suggest that these pigments could act as inhibitors of S protein, pointing them as antiviral drugs for SARS-CoV-2.<br>

scholarly journals Comprehensive O-glycosylation analysis of the SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Xuefang Dong ◽  
Cheng Chen ◽  
Jingyu Yan ◽  
Xiuling Li ◽  
Xinmiao Liang
Keyword(s):  
Public Health ◽  
Vaccine Development ◽  
Protein S ◽  
Spike Protein ◽  
Glycosylation Profile ◽  
Glycosylation Sites ◽  
Successful Vaccine ◽  
Public Health Threat ◽  
Biomimetic Polymer ◽  
Shed Light

Abstract The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a serious public health threat. Most vaccines being developed against SARS-CoV-2 target the highly glycosylated spike protein (S). A good knowledge of the glycosylation profile of this protein is key for successful vaccine development. Unlike the 22 confirmed N-glycosylation sites (NGSs) on the SARS-CoV-2 S, only a few O-glycosylation sites (OGSs) on this protein have been reported. This difference is mainly ascribed to an extremely low O-glycosylation stoichiometry. Herein, we comprehensively analyzed the O-glycosylation profile of recombinant SARS-CoV-2 S employing biomimetic polymer consisting of Trp-Arg monomer. Twenty-six OGSs and 33 O-linked glycans (OLGs) in the SARS-CoV-2 S were unambiguously identified, among which 24 OGSs and 25 OLGs are novel to the SARS-CoV-2 S. Our study reveals the comprehensive O-glycosylation profile of the SARS-CoV-2 S, which might shed light on viral pathobiology and assist in vaccine development.

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