scholarly journals Evolutionary and Antigenic Profiling of the Tendentious D614G Mutation of SARS-CoV-2 in Gujarat, India

2021 ◽  
Vol 12 ◽  
Author(s):  
Jay Nimavat ◽  
Chandrashekar Mootapally ◽  
Neelam M. Nathani ◽  
Devyani Dave ◽  
Mukesh N. Kher ◽  
...  
Keyword(s):  
Spike Protein ◽  
The Novel ◽  
Very High Frequency ◽  
Gujarat State ◽  
Viral Genomes ◽  
Public Repositories ◽  
Novel Coronavirus ◽  
Protein Variants ◽  
Affected Country ◽  
Significant Attention

Humankind has suffered many pandemics in history including measles, SARS, MERS, Ebola, and recently the novel Coronavirus disease caused by SARS-CoV-2. As of September 2021, it has affected over 200 million people and caused over 4 million deaths. India is the second most affected country in the world. Up to this date, more than 38 Lakh viral genomes have been submitted to public repositories like GISAID and NCBI to analyze the virus phylogeny and mutations. Here, we analyzed 2349 genome sequences of SARS-CoV-2 submitted in GISAID by a single institute pertaining to infections from the Gujarat state to know their variants and phylogenetic distributions with a major focus on the spike protein. More than 93% of the genomes had one or more mutations in the spike glycoprotein. The D614G variant in spike protein is reported to have a very high frequency of >95% globally followed by the L452R and P681R, thus getting significant attention. The antigenic propensity of a small peptide of 29 residues from 597 to 625 of the spike protein variants having D614 and G614 showed that G614 has a little higher antigenic propensity. Thus, the D614G is the cause for higher viral antigenicity, however, it has not been reported to be effective to be causing more deaths.

scholarly journals Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 57
Author(s):  
Zhi-Ling Zhu ◽  
Xiao-Dan Qiu ◽  
Shuo Wu ◽  
Yi-Tong Liu ◽  
Ting Zhao ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Blocking Effect ◽  
Spike Protein ◽  
Binding Affinities ◽  
The Novel ◽  
Converting Enzyme ◽  
Primary Method ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Effective Drugs

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.

scholarly journals Synthesis and immunological evaluation of synthetic peptide based anti-SARS-CoV-2 vaccine candidates

2021 ◽  
Author(s):  
Qingyu Zhao ◽  
Yanan Gao ◽  
Min Xiao ◽  
Xuefei Huang ◽  
Xuanjun Wu
Keyword(s):  
Synthetic Peptide ◽  
Spike Protein ◽  
Effective Vaccine ◽  
The Novel ◽  
Vaccine Candidates ◽  
Peptide Epitopes ◽  
Novel Coronavirus ◽  
Immunological Evaluation

For prevention of the coronavirus disease 2019 caused by the novel coronavirus SARS-CoV-2, an effective vaccine is critical. Herein, several potential peptide epitopes from the spike protein of SARS-CoV-2 have...

Nanovaccine: A hope to triumph the battle against novel Coronavirus disease 2019 (COVID-19)

2021 ◽  
Vol 15 ◽  
Author(s):  
Anurag Singh ◽  
Anand Maurya ◽  
Gaurav Mishra ◽  
Rajendra Awasthi ◽  
Kamal Dua ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Goblet Cells ◽  
Spike Protein ◽  
Effective Vaccine ◽  
The Novel ◽  
Infection Site ◽  
Peptide Vaccines ◽  
Ciliated Cells ◽  
Novel Coronavirus ◽  
Major Target

Background: The novel coronavirus 2019 (COVID-19) infection has caused the global emergence of coronavirus in humans during the last 12 months. Till May 11, 2021, the confirmed global COVID-19 cases and deaths reached 158551526 and 3296855, respectively. Methods: Goblet cells and ciliated cells in the nose act as the initial infection site of SARS-CoV-2. Thus, mucus immunity is important to protect from infection. The outburst of SARS-CoV-2 infection can be halted only when an effective vaccine will be developed. Results: Globally, over 100 different vaccines are under investigation, including DNA vaccines, RNA vaccines, inactivated virus vaccines, adenovirus-based vaccines, recombinant/ subunit protein vaccines, peptide vaccines, and virus-like particles etc. Inactivated virus vaccines and mRNA, and adenovirus-based vaccines have moved fast into clinical trials. Conclusion: : Vaccines containing spike protein of SARS-CoV as subunit could effectively prevent binding of coronavirus to the host cell and membrane fusion. Thus, spike protein can be used as a major target for subunit vaccine preparation.

scholarly journals The local topological free energy of the SARS-CoV-2 Spike protein

2021 ◽  
Author(s):  
Quenisha Baldwin ◽  
Bobby G Sumpter ◽  
Eleni Panagiotou
Keyword(s):  
Experimental Data ◽  
Mathematical Method ◽  
Density Functional Theory ◽  
Free Energy ◽  
Density Functional ◽  
Structural Rearrangement ◽  
Spike Protein ◽  
The Novel ◽  
Functional Theory ◽  
Novel Coronavirus

The novel coronavirus SARS-CoV-2 infects human cells using a mechanism that involves binding and structural rearrangement of its spike protein. Understanding protein rearrangement and identifying specific residues where mutations affect protein rearrangement has attracted a lot of attention for drug development. We use a mathematical method introduced in [9] to associate a local topological/geometrical free energy along the SARS-CoV-2 spike protein backbone. Our results show that the total local topological free energy of the SARS-CoV-2 spike protein monotonically decreases from pre-to post-fusion and that its distribution along the protein domains is related to their activity in protein rearrangement. By using density functional theory (DFT) calculations with inclusion of solvent effects, we show that high local topological free energy conformations are unstable compared to those of low topological free energy. By comparing to experimental data, we find that the high local topological free energy conformations in the spike protein are associated with mutations which have the largest experimentally observed effect to protein rearrangement.

scholarly journals Conservation analysis and screening of Ayurvedic compounds against SARS-CoV-2 Spike protein

2020 ◽  
Author(s):  
Zarrin Basharat ◽  
Muhammad Jahanzaib ◽  
Noor Rahman ◽  
Ishtiaq Ahmad Khan ◽  
Azra Yasmin
Keyword(s):  
Caspase 3 ◽  
Spike Protein ◽  
The Novel ◽  
Post Translational Modification ◽  
S Protein ◽  
Conservation Analysis ◽  
The Past ◽  
Online Tools ◽  
Novel Coronavirus ◽  
Over Time

Abstract Recent infections caused by the novel coronavirus (SARS-CoV-2) have led to global panic and mortality. Here, we analyzed the spike (S) protein of this virus using bioinformatics tools. We aimed to determine relative changes among different coronavirus species over the past two decades and to understand the conservation of the S-protein. Representative sequences of coronaviruses were collected from humans and other animals between 2000 and 2020. Evolutionary analyses found that the S-protein did not evolve overnight, but rather continuously over time. Post-translational modification (PTM) analysis using online tools and virtual screening of S-protein against a phytochemical database of Ayurvedic medicinal compounds (n = 2103) identified the S-protein inhibitors. Among these, top ranked were Gingerol (IUPAC name: 4'-Me ether, 3,5-di-Ac 3,5-di-Gingerdiols), 1-(5-Butyltetrahydro-2-furanyl)-2-hexacosanone and Ginsenoyne N ginseng that stimulates Caspase-3, Caspase-8, and the immune system. Gingerol is found in the fresh ginger and has reputation of being a potent antiviral. These compounds might prove useful to design drugs against COVID-19.

scholarly journals ACE-2-derived Biomimetic Peptides for the Inhibition of Spike Protein of SARS-CoV-2

2020 ◽  
Author(s):  
Saroj Kumar Panda ◽  
Parth Sarthi Sen Gupta ◽  
Satyaranjan Biswal ◽  
Abhik Kumar Ray ◽  
Malay Kumar Rana
Keyword(s):  
Principal Component ◽  
Host Cells ◽  
Spike Protein ◽  
Peptide Inhibitor ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Inhibition Assay ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus

<p>SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein-hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields two-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide-inhibitor of the novel coronavirus. The binding of the spike protein and the best peptide-inhibitor with hACE-2 is explored further by molecular dynamics, free energy, and principal component analysis to demonstrate its efficacy. Further, the inhibition assay study with the best peptide inhibitor is in progress. </p>

scholarly journals “Monoclonal-type” plastic antibodies for SARS-CoV-2 based on Molecularly Imprinted Polymers

2020 ◽  
Author(s):  
Ortensia Ilaria Parisi ◽  
Marco Dattilo ◽  
Francesco Patitucci ◽  
Rocco Malivindi ◽  
Vincenzo Pezzi ◽  
...  
Keyword(s):  
Light Scattering ◽  
Molecularly Imprinted Polymers ◽  
Polymeric Nanoparticles ◽  
Infection Process ◽  
Spike Protein ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Molecularly Imprinted ◽  
Imprinted Polymers ◽  
Novel Coronavirus

Summary of the ideaOur idea is focused on the development of “monoclonal-type” plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein to block its function and, thus, the infection process. Molecular Imprinting, indeed, represents a very promising and attractive technology for the synthesis of MIPs characterized by specific recognition abilities for a target molecule. Given these characteristics, MIPs can be considered tailor-made synthetic antibodies obtained by a templating process.In the present study, the developed imprinted polymeric nanoparticles were characterized in terms of particles size and distribution by Dynamic Light Scattering (DLS) and the imprinting effect and selectivity were investigated by performing binding experiments using the receptor-binding domain (RBD) of the novel coronavirus and the RBD of SARS-CoV spike protein, respectively. Finally, the hemocompatibility of the prepared MIP-based plastic antibodies was also evaluated.

The insights of novel coronavirus disease 2019 (COVID-19): Current understanding, research and therapeutic updates

2021 ◽  
Vol 15 ◽  
Author(s):  
Dudala Sai Sushma ◽  
Varun Jaiswal ◽  
Arvind Verma ◽  
Asha Sharma ◽  
Tarun Pal
Keyword(s):  
Vaccine Development ◽  
Current Understanding ◽  
Effective Vaccine ◽  
The Novel ◽  
Biological Drugs ◽  
Plasma Therapy ◽  
Approaches To Study ◽  
Public Repositories ◽  
Novel Coronavirus ◽  
Patented Inventions

Background: Humans can be infected with various coronaviruses that cause serious illness and death. One such pandemic strain of coronavirus was recently identified in December 2019 and lead to a devastating outbreak in Wuhan city of China. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is highly contagious which causes symptoms such as fever, cough and shortness of breath. Objective: The objective of this review is to highlight the current understanding, research and therapeutic updates of the novel coronavirus disease 2019 (COVID-19). Methods: A thorough literature search was conducted for research papers and patents in context to COVID-19. All articles with respect to this subject was taken from various public repositories such as Google Scholar, Pubmed, ScienceDirect (Elsevier), Springer, Web of Science, etc. Results: The present analysis showed that key areas of the inventions were the vaccines and diagnostic kits apart from the composition for the treatment of CoV. It was also observed that no specific vaccine treatments are available for the treatment of 2019-nCov; however, developing novel chemical or biological drugs and kits for early diagnosis, prevention, and disease management is the primary governing topic among the patented inventions. The present study also indicates potential research opportunities for the future, particularly to combat 2019-nCoV. The current focus of the researches has turned towards developing four potential treatments including development of candidate vaccine, development of novel potential drugs, repurposing of existing drugs and development of convalescent plasma therapy. The PCR based diagnosis is the gold standard for the COVID-19 testing but it require resource time, expertise and high associated cost hence the researchers are also developing different diagnosis methods for the COVID-19. Although vaccines are being developed by various companies and have passed the pre-clinical stages but still there exists no guarantee for these to become the effective vaccine. The current treatments which are being used for COVID-19 patients are not well established and have limited success. Conclusion: The pandemic has challenged the medical, economic and public health infrastructure across globe. There is urgent need to explore all available and possible methods/approaches to study this disease for drug and vaccine development at the earliest.

scholarly journals Design and Numerical Analysis of a Graphene-Coated SPR Biosensor for Rapid Detection of the Novel Coronavirus

Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3491
Author(s):  
Tarik Bin Abdul Akib ◽  
Samia Ferdous Mou ◽  
Md. Motiur Rahman ◽  
Md. Masud Rana ◽  
Md. Rabiul Islam ◽  
...  
Keyword(s):  
Refractive Index ◽  
Surface Plasmon ◽  
Rapid Detection ◽  
Detection Sensitivity ◽  
Spike Protein ◽  
Detection Accuracy ◽  
The Novel ◽  
Spr Biosensor ◽  
Highly Sensitive ◽  
Novel Coronavirus

In this paper, a highly sensitive graphene-based multiple-layer (BK7/Au/PtSe2/Graphene) coated surface plasmon resonance (SPR) biosensor is proposed for the rapid detection of the novel Coronavirus (COVID-19). The proposed sensor was modeled on the basis of the total internal reflection (TIR) technique for real-time detection of ligand-analyte immobilization in the sensing region. The refractive index (RI) of the sensing region is changed due to the interaction of different concentrations of the ligand-analyte, thus impacting surface plasmon polaritons (SPPs) excitation of the multi-layer sensor interface. The performance of the proposed sensor was numerically investigated by using the transfer matrix method (TMM) and the finite-difference time-domain (FDTD) method. The proposed SPR biosensor provides fast and accurate early-stage diagnosis of the COVID-19 virus, which is crucial in limiting the spread of the pandemic. In addition, the performance of the proposed sensor was investigated numerically with different ligand-analytes: (i) the monoclonal antibodies (mAbs) as ligand and the COVID-19 virus spike receptor-binding domain (RBD) as analyte, (ii) the virus spike RBD as ligand and the virus anti-spike protein (IgM, IgG) as analyte and (iii) the specific probe as ligand and the COVID-19 virus single-standard ribonucleic acid (RNA) as analyte. After the investigation, the sensitivity of the proposed sensor was found to provide 183.33°/refractive index unit (RIU) in SPR angle (θSPR) and 833.33THz/RIU in SPR frequency (SPRF) for detection of the COVID-19 virus spike RBD; the sensitivity obtained 153.85°/RIU in SPR angle and 726.50THz/RIU in SPRF for detection of the anti-spike protein, and finally, the sensitivity obtained 140.35°/RIU in SPR angle and 500THz/RIU in SPRF for detection of viral RNA. It was observed that whole virus spike RBD detection sensitivity is higher than that of the other two detection processes. Highly sensitive two-dimensional (2D) materials were used to achieve significant enhancement in the Goos-Hänchen (GH) shift detection sensitivity and plasmonic properties of the conventional SPR sensor. The proposed sensor successfully senses the COVID-19 virus and offers additional (1 + 0.55) × L times sensitivity owing to the added graphene layers. Besides, the performance of the proposed sensor was analyzed based on detection accuracy (DA), the figure of merit (FOM), signal-noise ratio (SNR), and quality factor (QF). Based on its performance analysis, it is expected that the proposed sensor may reduce lengthy procedures, false positive results, and clinical costs, compared to traditional sensors. The performance of the proposed sensor model was checked using the TMM algorithm and validated by the FDTD technique.

scholarly journals Characterization of structural and energetic differences between conformations of the SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Rodrigo A. Moreira ◽  
Horacio V. Guzman ◽  
Subramanian Boopathi ◽  
Joseph L. Baker ◽  
Adolfo B. Poma
Keyword(s):  
Structural Stability ◽  
Drug Targets ◽  
Dynamic Contact ◽  
Cell Entry ◽  
New Drugs ◽  
Spike Protein ◽  
The Novel ◽  
Poisson Boltzmann ◽  
Novel Coronavirus

AbstractThe novel coronavirus disease 2019 (COVID-19) pandemic has disrupted modern societies and their economies. The resurgence in COVID-19 cases as part of the second wave is observed across Europe and the Americas. The scientific response has enabled a complete structural characterization of the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-CoV-2). Among the most relevant proteins required by the novel coronavirus to facilitate the cell entry mechanism is the spike protein trimer. This protein possesses a receptor-binding domain (RBD) that binds the cellular angiotensin-converting enzyme 2 (ACE2) and then triggers the fusion of viral and host cell membranes. In this regard, a comprehensive characterization of the structural stability of the spike protein is a crucial step to find new therapeutics to interrupt the process of recognition. On the other hand, it has been suggested the participation of more than one RBD as a possible mechanism to enhance cell entry. Here we discuss the protein structural stability based on the computational determination of the dynamic contact map and the energetic difference of the spike protein conformations via the mapping of the hydration free energy by the Poisson-Boltzmann method. We expect our result to foster the discussion of the number of RBD involved during recognition and the repurposing of new drugs to disable the recognition by discovering new hotspots for drug targets apart from the flexible loop in the RBD that binds the ACE2.

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