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 Designing of a novel multisubunit vaccine against Nipah virus structural proteins: A reverse vaccinology approach

2021 ◽  
Author(s):  
khalid Mohamed Adam
Keyword(s):  
Nipah Virus ◽  
Reverse Vaccinology ◽  
Structural Proteins ◽  
Effective Vaccine ◽  
Compact Structure ◽  
Grand Average ◽  
Physiochemical Parameters ◽  
Significant Public Health ◽  
Aliphatic Index ◽  
Stable Molecule

Abstract Background The significant public health risk posed by NiV zoonosis and the lack of effective countermeasures against the intermittent outbreaks of the disease in the South and Southeast Asia region have entailed an imperative search for a protective vaccine to prevent or mitigate its epidemic potentiality. This is an endeavor to design an effective, safe multisubunit vaccine using an in silico reverse vaccinology approach. Methods The epitopes used for the construction of the candidate vaccine were meticulously predicted from five viral structural proteins (G, F, M, N, P) using several immunoinformatics tools to assess different epitope characteristics, namely, VaxiJen server for antigenicity, IEDB immunogenicity tool for immunogenicity, AlgPred server for allergenicity, ToxinPred for toxigenicity, IFNepitope server for interferon-gamma induction, Protparam server for physicochemical properties, GROMACS for simulation and simulation dynamics analysis, and finally, SnapGene tool for molecular cloning. Results The proposed vaccine molecule consisted of 501 amino acids, encompassing 7 B cell epitopes, 14 CTL epitopes, and 4 HTL epitopes. The physiochemical parameters of the vaccine construct showed a molecular weight of 54.6 kDa, an acidic stable molecule with an instability index of 38.3, aliphatic index of 62.89, and grand average of hydropathicity of -0.476. Moreover, the docking results and simulation dynamics of the vaccine molecule and TLR-3 showed global energy of 1.58 Kcal/mol, atomic contact energy of 2.98 Kcal/mol, and RMSD of 0.65 nm. The radius gyration showed a relatively steady value throughout the simulation period. a suggestive result of a stable compact structure and a promisingly effective vaccine construct. Conclusion In summary, the overall results of the multi-subunit vaccine molecule are suggestive of a promisingly effective vaccine against NiV infection in humans with a relatively stable compact structure, however, further experimental validation and assessment of pathogenic priming and autoimmunity induction are recommended.

scholarly journals Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals

2020 ◽  
Vol 6 (45) ◽  
pp. eabc9999 ◽  
Author(s):  
Yuanmei Zhu ◽  
Danwei Yu ◽  
Yang Han ◽  
Hongxia Yan ◽  
Huihui Chong ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Full Length ◽  
Receptor Binding Domain ◽  
Serum Antibodies ◽  
Serum Samples ◽  
S Protein ◽  
Novel Coronavirus

The current coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus genetically close to SARS-CoV. To investigate the effects of previous SARS-CoV infection on the ability to recognize and neutralize SARS-CoV-2, we analyzed 20 convalescent serum samples collected from individuals infected with SARS-CoV during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor binding domain (RBD) of SARS-CoV; cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2; and neutralized both SARS-CoV and SARS-CoV-2 S protein–driven infections. Analysis of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV verified cross-reactive neutralization against SARS-CoV-2. A SARS-CoV–derived RBD from palm civets elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing strategies for development of universal vaccines against emerging coronaviruses.

scholarly journals A Review of SARS-CoV-2, Responsible for COVID-19: History, Biology, Infection Mechanism, Antigenic Vaccines, their Risks and How an Alternate RBD Vaccine is Safer?

2021 ◽  
Author(s):  
Z.M.G. Sarwar Jahangir ◽  
Arleta Helena Marnik
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Somatic Cell ◽  
Antibody Production ◽  
Spike Protein ◽  
Protein Antigen ◽  
Effective Vaccine ◽  
S Protein ◽  
Infection Mechanism ◽  
Fast Acting ◽  
Stimulate Antibody

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

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 Maturation of T and B Lymphocytes in the Assessment of the Immune Status in COVID-19 Patients

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2615
Author(s):  
Iwona Kwiecień ◽  
Elżbieta Rutkowska ◽  
Krzysztof Kłos ◽  
Ewa Więsik-Szewczyk ◽  
Karina Jahnz-Różyk ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
X Ray ◽  
Healthy Control ◽  
Chest X Ray ◽  
Novel Coronavirus ◽  
And Control ◽  
B And T Lymphocytes

Cell response to novel coronavirus disease 19 (COVID-19) is currently a widely researched topic. The assessment of leukocytes population and the maturation of both B and T lymphocytes may be important in characterizing the immunological profile of COVID-19 patients. The aim of the present study was to evaluate maturation of B and T cells in COVID-19 patients with interstitial lesions on chest X-ray (COVID-19 X-ray (+)), without changes on X-ray (COVID-19 X-ray (−)) and in healthy control. The study group consisted of 23 patients divided on two groups: COVID-19 X-ray (+) n = 14 and COVID-19 X-ray (−) n = 9 and control n = 20. The flow cytometry method was performed. We observed a significantly higher percentage of plasmablasts and lower CD4+ lymphocytes in COVID-19 X-ray (+) patients than in COVID-19 X-ray (−) and control. In the COVID-19 X-ray (+) patients, there was a lower proportion of effector CD4+ T cells, naïve CD8+ T cells and higher central memory CD4+ cells and effector CD8+ T cells than control. The above results showed that the assessment of selected cells of B and T lymphocytes by flow cytometry can distinguish patients with COVID-19 and differentiate patients with and without changes on chest X-ray.

scholarly journals A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells

2020 ◽  
Author(s):  
Zhaoqian Su ◽  
Yinghao Wu
Keyword(s):  
Life Cycle ◽  
Severe Acute Respiratory Syndrome ◽  
Structural Model ◽  
Computational Study ◽  
Simulation Method ◽  
Multiscale Simulation ◽  
Host Cells ◽  
S Protein ◽  
New Type ◽  
Novel Coronavirus

ABSTRACTThe respiratory syndrome caused by a new type of coronavirus has been emerging from China and caused more than one million death globally since December 2019. This new virus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the same receptor called Angiotensin-converting enzyme 2 (ACE2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (SARS) seventeen years ago. Both viruses recognize ACE2 through the spike proteins (S-protein) on their surfaces. It was found that the S-protein from the SARS coronavirus (SARS-CoV) bind stronger to ACE2 than SARS-CoV-2. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 and the S-protein from SARS-CoV-2, so that the rate of their association can be estimated and compared with the binding of S-protein from SARS-CoV by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that this new pandemic by far spread much faster than SARS.

scholarly journals A Review of SARS-CoV-2, Responsible for COVID-19: History, Biology, Infection Mechanism, Antigenic Vaccines, Their Risks and how an Alternate RBD Vaccine is Safer?

2021 ◽  
Author(s):  
Z.M.G. Sarwar Jahangir ◽  
Arleta Helena Marnik
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Somatic Cell ◽  
Antibody Production ◽  
Spike Protein ◽  
Protein Antigen ◽  
Effective Vaccine ◽  
S Protein ◽  
Infection Mechanism ◽  
Fast Acting ◽  
Stimulate Antibody

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

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 Identification of Two Neutralizing Regions on the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Produced from the Mammalian Expression System

2005 ◽  
Vol 79 (3) ◽  
pp. 1906-1910 ◽  
Author(s):  
Shixia Wang ◽  
Te-hui W. Chou ◽  
Pavlo V. Sakhatskyy ◽  
Song Huang ◽  
John M. Lawrence ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
High Titer ◽  
Expression System ◽  
Antibody Responses ◽  
Effective Vaccine ◽  
S Protein ◽  
Mammalian Expression ◽  
C Terminus ◽  
N Terminus ◽  
Specific Immunoglobulin

ABSTRACT The Spike (S) protein of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) plays important roles in viral pathogenesis and potentially in the development of an effective vaccine against this virulent infectious disease. In this study, the codon-optimized S gene of SARS-CoV was synthesized to construct DNA vaccine plasmids expressing either the full-length or segments of the S protein. High titer S-specific immunoglobulin G antibody responses were elicited in rabbits immunized with DNA against various segments of the S protein. Two neutralizing domains were identified on the S protein, one at the N terminus (Ser12-Thr535) and the other near the C terminus (Arg797-Ile1192).

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.

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