scholarly journals Structural and Drug Screening Analysis of the Non-structural Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 Virus Extracted From Indian Coronavirus Disease 2019 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Nupur Biswas ◽  
Krishna Kumar ◽  
Priyanka Mallick ◽  
Subhrangshu Das ◽  
Izaz Monir Kamal ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Drug Screening ◽  
Structural Information ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Host Protein ◽  
Structural Proteins ◽  
Effective Vaccine ◽  
Indian Patients ◽  
Novel Coronavirus

The novel coronavirus 2 (nCoV2) outbreaks took place in December 2019 in Wuhan City, Hubei Province, China. It continued to spread worldwide in an unprecedented manner, bringing the whole world to a lockdown and causing severe loss of life and economic stability. The coronavirus disease 2019 (COVID-19) pandemic has also affected India, infecting more than 10 million till 31st December 2020 and resulting in more than a hundred thousand deaths. In the absence of an effective vaccine, it is imperative to understand the phenotypic outcome of the genetic variants and subsequently the mode of action of its proteins with respect to human proteins and other bio-molecules. Availability of a large number of genomic and mutational data extracted from the nCoV2 virus infecting Indian patients in a public repository provided an opportunity to understand and analyze the specific variations of the virus in India and their impact in broader perspectives. Non-structural proteins (NSPs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus play a major role in its survival as well as virulence power. Here, we provide a detailed overview of the SARS-CoV2 NSPs including primary and secondary structural information, mutational frequency of the Indian and Wuhan variants, phylogenetic profiles, three-dimensional (3D) structural perspectives using homology modeling and molecular dynamics analyses for wild-type and selected variants, host-interactome analysis and viral–host protein complexes, and in silico drug screening with known antivirals and other drugs against the SARS-CoV2 NSPs isolated from the variants found within Indian patients across various regions of the country. All this information is categorized in the form of a database named, Database of NSPs of India specific Novel Coronavirus (DbNSP InC), which is freely available at http://www.hpppi.iicb.res.in/covid19/index.php.

scholarly journals In Silico Characterization of Surface Glycoprotein [QHD43416] of Severe Acute Respiratory Syndrome-Coronavirus 2

2020 ◽  
Vol 3 (2) ◽  
pp. 32-36
Author(s):  
Rajneesh Prajapat ◽  
◽  
Suman Jain ◽  
Manish K Vaishnav ◽  
Sonal Sogani ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
In Silico ◽  
Three Dimensional ◽  
Surface Glycoprotein ◽  
Dimensional Structure ◽  
Model Quality ◽  
Core Section ◽  
Novel Coronavirus ◽  
And Function ◽  
Tools And Techniques

The novel coronavirus (SARS-CoV-2) reported from Wuhan, China, that spread rapidly and cause severe acute respiratory syndrome. The disease associated with infection of SARS-CoV-2 that is referred as COVID-19 (Coronavirus Disease 2019). In the present study, the surface glycoprotein [QHD43416] of SARS-CoV-2 was characterized for structure analysis and validation to provide information about its three-dimensional structure by using in silico tools and techniques. The surface glycoprotein [QHD43416] sequence of SARS-CoV-2 was retrieved from NCBI and its PDB file was designed by using phyre2 server. The RAMPAGE and UCLA-DOE (Verify 3D) was used for analysis and validation of structure model of protein. The model quality estimation based on the ProSA. Alignment of surface glycoprotein [QHD43416], revealed homology (72% identity) with spike protein of bat coronavirus [BM48-31/BGR/2008]. The model corresponding to probability conformation with 90.5% residue of core section, 9.1 % of allowed section and 0.4 % residue of outer section in φ-ψ plot, that specifies accuracy of prediction model. The Verify 3D results shows that 59.53% residues have average 3D-1D score >= 0.2 this determines compatibility of 3D model with its amino acid sequence (1D). ProSA Z-score -11.19 represents the good quality of the model. The structure and function of coronavirus surface glycoprotein could be predicted by in silico modeling studies. The protein model will be further used for designing of vaccine / drug development against coronavirus infection.

scholarly journals Structural and energetic aspects of protein-protein recognition.

1997 ◽  
Vol 44 (3) ◽  
pp. 367-387 ◽  
Author(s):  
J Otlewski ◽  
W Apostoluk
Keyword(s):  
Conformational Changes ◽  
Growth Hormone Receptor ◽  
Structural Information ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Water Structure ◽  
Human Growth ◽  
Protein Recognition ◽  
Specific Recognition ◽  
Different Types

Specific recognition between proteins plays a crucial role in a great number of vital processes. In this review different types of protein-protein complexes are analyzed on the basis of their three-dimensional structures which became available in recent years. The complexes which are analyzed include: those resulting from different types of recognition between proteinase and protein inhibitor (canonical inhibitors of serine proteinases, hirudin, inhibitors of cysteine proteinases, carboxypeptidase inhibitor), barnase-barstar, human growth hormone-receptor and antibody-antigen. It seems obvious that specific and strong protein-protein recognition is achieved in many different ways. To further explore this question, the structural information was analyzed together with kinetic and thermodynamic data available for the respective complexes. It appears that the energy and rates of specific recognition of proteins are influenced by many different factors, including: area of interacting surfaces; complementarity of shapes, charges and hydrogen bonds; water structure at the interface; conformational changes; additivity and cooperativity of individual interactions, steric effects and various (conformational, hydration) entropy changes.

Use of Natural Compounds as a potential therapeutic agent against COVID-19

2021 ◽  
Vol 26 ◽  
Author(s):  
Shadma Wahab ◽  
Irfan Ahmad ◽  
Safia Irfan ◽  
Mohammad Hassan Baig ◽  
Abd-ElAziem Farouk ◽  
...  
Keyword(s):  
Natural Products ◽  
Severe Acute Respiratory Syndrome ◽  
Drug Development ◽  
Respiratory System ◽  
Crucial Role ◽  
Therapeutic Agent ◽  
Natural Compounds ◽  
Current Status ◽  
Effective Vaccine ◽  
Novel Coronavirus

: The current 2019-nCoV outbreak is becoming extremely noxious and has affected the whole world. Its control is challenging because there is no effective vaccine or drug available for Coronavirus disease. The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), previously named as 2019 novel Coronavirus (2019-nCoV), primarily targets the human respiratory system to lung lesions and lethal pneumonia. Natural products have always shown a crucial role in the process of drug development against various diseases. They could be leads for further drug development to combat emergent mutants of the coronavirus. In this review, the current status of natural compounds and their derivatives acting against different species of CoV are discussed.

scholarly journals Three-dimensional topology of the SMC2/SMC4 subcomplex from chicken condensin I revealed by cross-linking and molecular modelling

Open Biology ◽  
2015 ◽  
Vol 5 (2) ◽  
pp. 150005 ◽  
Author(s):  
Helena Barysz ◽  
Ji Hun Kim ◽  
Zhuo Angel Chen ◽  
Damien F. Hudson ◽  
Juri Rappsilber ◽  
...  
Keyword(s):  
Structure Prediction ◽  
Structural Information ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Coiled Coil ◽  
Coiled Coils ◽  
Dimensional Structure ◽  
Cross Linking ◽  
Mitotic Chromosomes ◽  
Essential Components

SMC proteins are essential components of three protein complexes that are important for chromosome structure and function. The cohesin complex holds replicated sister chromatids together, whereas the condensin complex has an essential role in mitotic chromosome architecture. Both are involved in interphase genome organization. SMC-containing complexes are large (more than 650 kDa for condensin) and contain long anti-parallel coiled-coils. They are thus difficult subjects for conventional crystallographic and electron cryomicroscopic studies. Here, we have used amino acid-selective cross-linking and mass spectrometry combined with structure prediction to develop a full-length molecular draft three-dimensional structure of the SMC2/SMC4 dimeric backbone of chicken condensin. We assembled homology-based molecular models of the globular heads and hinges with the lengthy coiled-coils modelled in fragments, using numerous high-confidence cross-links and accounting for potential irregularities. Our experiments reveal that isolated condensin complexes can exist with their coiled-coil segments closely apposed to one another along their lengths and define the relative spatial alignment of the two anti-parallel coils. The centres of the coiled-coils can also approach one another closely in situ in mitotic chromosomes. In addition to revealing structural information, our cross-linking data suggest that both H2A and H4 may have roles in condensin interactions with chromatin.

scholarly journals Vaccinomic approach for novel multi epitopes vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yassir A. Almofti ◽  
Khoubieb Ali Abd-elrahman ◽  
Elsideeq E. M. Eltilib
Keyword(s):  
Binding Energy ◽  
T Lymphocytes ◽  
Severe Acute Respiratory Syndrome ◽  
Tertiary Structure ◽  
Effective Vaccine ◽  
S Protein ◽  
Grand Average ◽  
Aliphatic Index ◽  
Novel Coronavirus ◽  
B And T Lymphocytes

Abstract Background The spread of a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in China and other countries is of great concern worldwide with no effective vaccine. This study aimed to design a novel vaccine construct against SARS-CoV-2 from the spike S protein and orf1ab polyprotein using immunoinformatics tools. The vaccine was designed from conserved epitopes interacted against B and T lymphocytes by the combination of highly immunogenic epitopes with suitable adjuvant and linkers. Results The proposed vaccine composed of 526 amino acids and was shown to be antigenic in Vaxigen server (0.6194) and nonallergenic in Allertop server. The physiochemical properties of the vaccine showed isoelectric point of 10.19. The instability index (II) was 31.25 classifying the vaccine as stable. Aliphatic index was 84.39 and the grand average of hydropathicity (GRAVY) was − 0.049 classifying the vaccine as hydrophilic. Vaccine tertiary structure was predicted, refined and validated to assess the stability of the vaccine via Ramachandran plot and ProSA-web servers. Moreover, solubility of the vaccine construct was greater than the average solubility provided by protein sol and SOLpro servers indicating the solubility of the vaccine construct. Disulfide engineering was performed to reduce the high mobile regions in the vaccine to enhance stability. Docking of the vaccine construct with TLR4 demonstrated efficient binding energy with attractive binding energy of − 338.68 kcal/mol and − 346.89 kcal/mol for TLR4 chain A and chain B respectively. Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells and INF-γ. Upon cloning, the vaccine protein was reverse transcribed into DNA sequence and cloned into pET28a(+) vector to ensure translational potency and microbial expression. Conclusion A unique vaccine construct from spike S protein and orf1ab polyprotein against B and T lymphocytes was generated with potential protection against the pandemic. The present study might assist in developing a suitable therapeutics protocol to combat SARSCoV-2 infection.

scholarly journals AI-based spectroscopic monitoring of real-time interactions between SARS-CoV-2 and human ACE2

2021 ◽  
Vol 118 (26) ◽  
pp. e2025879118
Author(s):  
Sheng Ye ◽  
Guozhen Zhang ◽  
Jun Jiang
Keyword(s):  
Machine Learning ◽  
Ir Spectra ◽  
Real Time ◽  
Structural Information ◽  
Protein Complexes ◽  
Time Resolved ◽  
S Protein ◽  
Spectroscopic Monitoring ◽  
Quantum Chemistry Calculations ◽  
Novel Coronavirus

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invades a human cell via human angiotensin-converting enzyme 2 (hACE2) as the entry, causing the severe coronavirus disease (COVID-19). The interactions between hACE2 and the spike glycoprotein (S protein) of SARS-CoV-2 hold the key to understanding the molecular mechanism to develop treatment and vaccines, yet the dynamic nature of these interactions in fluctuating surroundings is very challenging to probe by those structure determination techniques requiring the structures of samples to be fixed. Here we demonstrate, by a proof-of-concept simulation of infrared (IR) spectra of S protein and hACE2, that time-resolved spectroscopy may monitor the real-time structural information of the protein−protein complexes of interest, with the help of machine learning. Our machine learning protocol is able to identify fine changes in IR spectra associated with variation of the secondary structures of S protein of the coronavirus. Further, it is three to four orders of magnitude faster than conventional quantum chemistry calculations. We expect our machine learning protocol would accelerate the development of real-time spectroscopy study of protein dynamics.

scholarly journals Protein domain-based structural interfaces help interpret biologically-relevant interactions in the human interaction network

2020 ◽  
Author(s):  
Krishna Praneeth Kilambi ◽  
Qifang Xu ◽  
Guruharsha Kuthethur Gururaj ◽  
Kejie Li ◽  
Spyros Artavanis-Tsakonas ◽  
...  
Keyword(s):  
Structural Information ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Interacting Proteins ◽  
Ppi Network ◽  
Human Interactome ◽  
Protein Protein Interaction ◽  
Binding Domains ◽  
Structural Coverage ◽  
Quality Map

AbstractA high-quality map of the human protein–protein interaction (PPI) network can help us better understand complex genotype–phenotype relationships. Each edge between two interacting proteins supported through an interface in a three-dimensional (3D) structure of a protein complex adds credibility to the biological relevance of the interaction. Such structure-supported interactions would augment an interaction map primarily built using high-throughput cell-based biophysical methods. Here, we integrate structural information with the human PPI network to build the structure-supported human interactome, a subnetwork of PPI between proteins that contain domains or regions known to form interfaces in the 3D structures of protein complexes. We expand the coverage of our structure-supported human interactome by using Pfam-based domain definitions, whereby we include homologous interactions if a human complex structure is unavailable. The structure-supported interactome predicts one-eighth of the total network PPI to interact through domain–domain interfaces. It identifies with higher resolution the interacting subunits in multi-protein complexes and enables us to characterize functional and disease-relevant neighborhoods in the network map with higher accuracy, allowing for structural insights into disease-associated genes and pathways. We expand the structural coverage beyond domain–domain interfaces by identifying the most common non-enzymatic peptide-binding domains with structural support. Adding these interactions between protein domains on one side and peptide regions on the other approximately doubles the number of structure-supported PPI. The human structure-supported interactome is a resource to prioritize investigations of smaller-scale context-specific experimental PPI neighborhoods of biological or clinical significance.Short abstractA high-quality map of the human protein–protein interaction (PPI) network can help us better understand genotype–phenotype relationships. Each edge between two interacting proteins supported through an interface in a three-dimensional structure of a protein complex adds credibility to the biological relevance of the interaction aiding experimental prioritization. Here, we integrate structural information with the human interactome to build the structure-supported human interactome, a subnetwork of PPI between proteins that contain domains or regions known to form interfaces in the structures of protein complexes. The structure-supported interactome predicts one-eighth of the total PPI to interact through domain–domain interfaces. It identifies with higher resolution the interacting subunits in multi-protein complexes and enables us to structurally characterize functional, disease-relevant network neighborhoods. We also expand the structural coverage by identifying PPI between non-enzymatic peptide-binding domains on one side and peptide regions on the other, thereby doubling the number of structure-supported PPI.

scholarly journals Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine

2004 ◽  
Vol 85 (10) ◽  
pp. 3109-3113 ◽  
Author(s):  
Hai Pang ◽  
Yinggang Liu ◽  
Xueqing Han ◽  
Yanhui Xu ◽  
Fuguo Jiang ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Structural Proteins ◽  
Effective Vaccine ◽  
S Protein ◽  
M Proteins ◽  
Humoral Responses

Some of the structural proteins of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) carry major epitopes involved in virus neutralization and are essential for the induction of protective humoral responses and the development of an effective vaccine. Rabbit antisera were prepared using full-length N and M proteins and eight expressed fragments covering the S protein. Antisera to S and M proteins were found to have different neutralizing titres towards SARS-CoV infection in vivo, ranging from 1 : 35 to 1 : 128. Antiserum to the N protein did not contain neutralizing antibodies. Epitopes inducing protective humoral responses to virus infection were located mainly in the M protein and a region spanning residues 13–877 of the S protein. The neutralizing ability of antisera directed against the expressed structural proteins was greater than that of convalescent patient antisera, confirming that, as immunogens, the former induce strong, SARS-CoV-specific neutralizing antibody responses. The in vitro neutralization assay has important implications for the design of an effective, protein-based vaccine preventing SARS-CoV infection.

Two-Dimensional Crystallization of Tetanus Toxin

1985 ◽  
Vol 43 ◽  
pp. 528-529
Author(s):  
Jeffry A. Reidler ◽  
John P. Robinson
Keyword(s):  
Electron Microscopy ◽  
Tetanus Toxin ◽  
Structural Information ◽  
Three Dimensional ◽  
Two Dimensional ◽  
Membrane Interface ◽  
3D Reconstructions ◽  
Cellular Receptors ◽  
Computer Reconstruction ◽  
2D Crystals

We have prepared two-dimensional (2D) crystals of tetanus toxin using procedures developed by Uzgiris and Kornberg for the directed production of 2D crystals of monoclonal antibodies at an antigen-phospholipid monolayer interface. The tetanus toxin crystals were formed using a small mole fraction of the natural receptor, GT1, incorporated into phosphatidyl choline monolayers. The crystals formed at low concentration overnight. Two dimensional crystals of this type are particularly useful for structure determination using electron microscopy and computer image refinement. Three dimensional (3D) structural information can be derived from these crystals by computer reconstruction of photographs of toxin crystals taken at different tilt angles. Such 3D reconstructions may help elucidate the mechanism of entry of the enzymatic subunit of toxins into cells, particularly since these crystals form directly on a membrane interface at similar concentrations of ganglioside GT1 to the natural cellular receptors.

EMCAT: An automatic image-processing system for electron-microscopic tomography

1994 ◽  
Vol 52 ◽  
pp. 418-419
Author(s):  
Weiping Liu ◽  
John W. Sedat ◽  
David A. Agard
Keyword(s):  
Image Processing ◽  
Structural Information ◽  
Imaging Technique ◽  
Three Dimensional ◽  
Processing System ◽  
Electron Microscopic ◽  
Data Set ◽  
Ordered Structures ◽  
Automatic Image Processing ◽  
Em Tomography

Any real world object is three-dimensional. The principle of tomography, which reconstructs the 3-D structure of an object from its 2-D projections of different view angles has found application in many disciplines. Electron Microscopic (EM) tomography on non-ordered structures (e.g., subcellular structures in biology and non-crystalline structures in material science) has been exercised sporadically in the last twenty years or so. As vital as is the 3-D structural information and with no existing alternative 3-D imaging technique to compete in its high resolution range, the technique to date remains the kingdom of a brave few. Its tedious tasks have been preventing it from being a routine tool. One keyword in promoting its popularity is automation: The data collection has been automated in our lab, which can routinely yield a data set of over 100 projections in the matter of a few hours. Now the image processing part is also automated. Such automations finish the job easier, faster and better.

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