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 Sequence 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):  
Immune System ◽  
Caspase 3 ◽  
Spike Protein ◽  
Caspase 8 ◽  
The Novel ◽  
S Protein ◽  
Conservation Analysis ◽  
The Past ◽  
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. 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 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 Fluorescent glycan fingerprinting of SARS2 spike proteins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhengliang L. Wu ◽  
James M. Ertelt
Keyword(s):  
Sialic Acid ◽  
Gel Electrophoresis ◽  
Fluorescent Labeling ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Quick Method ◽  
New Techniques ◽  
S Protein ◽  
Sds Page ◽  
Novel Coronavirus

AbstractGlycosylation is the most common post-translational modification and has myriad of biological functions. However, glycan analysis has always been a challenge. Here, we would like to present new techniques for glycan fingerprinting based on enzymatic fluorescent labeling and gel electrophoresis. The method is illustrated on SARS2 spike (S) glycoproteins. SARS2, a novel coronavirus and the causative agent of the COVID-19 pandemic, has had significant social and economic impacts since the end of 2019. To obtain the N-glycan fingerprint of an S protein, glycans released from the protein are first labeled through enzymatic incorporation of fluorophore-conjugated sialic acid or fucose, then separated by SDS-PAGE, and finally visualized with a fluorescent imager. To identify the labeled glycans of a fingerprint, glycan standards and glycan ladders are enzymatically generated and run alongside the samples as references. By comparing the mobility of a labeled glycan to that of a glycan standard, the identity of glycans maybe determined. O-glycans can also be fingerprinted. Due to the lack of an enzyme for broad O-glycan release, O-glycans on the S protein can be labeled with fluorescent sialic acid and digested with trypsin to obtain labeled glycan peptides that are then separated by gel electrophoresis. Glycan fingerprinting could serve as a quick method for globally assessing the glycosylation of a specific glycoprotein.

scholarly journals Web Application for Statistical Tracking and Predicting the Evolution of Active Cases with the Novel Coronavirus (SARS-CoV-2)

2021 ◽  
pp. 70-74
Author(s):  
Iulia Clitan ◽  
◽  
Adela Puscasiu ◽  
Vlad Muresan ◽  
Mihaela Ligia Unguresan ◽  
...  
Keyword(s):  
Neural Network ◽  
Mathematical Model ◽  
Web Application ◽  
Point Of View ◽  
The Novel ◽  
End User ◽  
First Case ◽  
Novel Coronavirus ◽  
Second Wave ◽  
Over Time

Since February 2020, when the first case of infection with SARS COV-2 virus appeared in Romania, the evolution of COVID-19 pandemic continues to have an ascending allure, reaching in September 2020 a second wave of infections as expected. In order to understand the evolution and spread of this disease over time and space, more and more research is focused on obtaining mathematical models that are able to predict the evolution of active cases based on different scenarios and taking into account the numerous inputs that influence the spread of this infection. This paper presents a web responsive application that allows the end user to analyze the evolution of the pandemic in Romania, graphically, and that incorporates, unlike other COVID-19 statistical applications, a prediction of active cases evolution. The prediction is based on a neural network mathematical model, described from the architectural point of view.

scholarly journals Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Xingyi Guo ◽  
Zhishan Chen ◽  
Yumin Xia ◽  
Weiqiang Lin ◽  
Hongzhi Li
Keyword(s):  
Genetic Variation ◽  
The Novel ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Missense Variants ◽  
Catalytic Metal ◽  
Using Data ◽  
Novel Coronavirus ◽  
Insight Into

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

Identification of a novel neutralizing epitope on the N-terminal domain of the HCoV-229E spike protein

2021 ◽  
Author(s):  
Jiale Shi ◽  
Yuejun Shi ◽  
Ruixue Xiu ◽  
Gang Wang ◽  
Rui Liang ◽  
...  
Keyword(s):  
Epitope Mapping ◽  
Vaccine Development ◽  
Selective Pressure ◽  
Spike Protein ◽  
Neutralizing Epitope ◽  
Change Over Time ◽  
S Protein ◽  
Terminal Domain ◽  
Neutralizing Epitopes ◽  
Over Time

The receptor binding domain (RBD) of the coronavirus spike protein (S) has been verified to be the main target for potent neutralizing antibodies (nAbs) in most coronaviruses, and the N-terminal domain (NTD) of some betacoronaviruses has also been indicated to induce nAbs. For alphacoronavirus HCoV-229E, its RBD has been shown to have neutralizing epitopes, and these epitopes could change over time. However, whether neutralizing epitopes exist on the NTD and whether these epitopes change like those of the RBD are still unknown. Here, we verified that neutralizing epitopes exist on the NTD of HCoV-229E. Furthermore, we characterized an NTD targeting nAb 5H10, which could neutralize both pseudotyped and authentic HCoV-229E VR740 in vitro. Epitope mapping indicated that 5H10 targeted motif E1 (147-167 aa) and identified F159 as critical for 5H10 binding. More importantly, our results revealed that motif E1 was highly conserved among clinical isolates except for F159. Further data proved that mutations at position 159 gradually appeared over time and could completely abolish the neutralizing ability of 5H10, supporting the notion that position 159 may be under selective pressure during the human epidemic. In addition, we also found that contemporary clinical serum has a stronger binding capacity for the NTD of contemporary strains than historic strains, proving that the epitope on the NTD could change over time. In summary, these findings define a novel neutralizing epitope on the NTD of HCoV-229E S and provide a theoretical basis for the design of vaccines against HCoV-229E or related coronaviruses. Importance Characterization of the neutralizing epitope of the spike (S) protein, the major invasion protein of coronaviruses, can help us better understand the evolutionary characteristics of these viruses and promote vaccine development. To date, the neutralizing epitope distribution of alphacoronaviruses is not well known. Here, we identified a neutralizing antibody that targeted the N-terminal domain (NTD) of the alphacoronavirus HCoV-229E S protein. Epitope mapping revealed a novel epitope that was not previously discovered in HCoV-229E. Further studies identified an important residue, F159. Mutations that gradually appeared over time at this site abolished the neutralizing ability of 5H10, indicating that selective pressure occurred at this position in the spread of HCoV-229E. Furthermore, we found that the epitopes within the NTD also changed over time. Taken together, our findings defined a novel neutralizing epitope and highlighted the role of the NTD in the future prevention and control of HCoV-229E or related coronaviruses.

Progress in Railway Mechanical Engineering 2019 – 2020 Survey – Locomotives

2021 ◽  
Author(s):  
Timothy Mast
Keyword(s):  
Mechanical Engineering ◽  
The Novel ◽  
The Past ◽  
Look Back ◽  
Class 1 ◽  
Novel Coronavirus

Abstract This survey reports on motive power developments for the previous year ending in August 2020. Invitations to collaborate were sent to several locomotive builders and railroads. The survey looks at the scope of new and rebuilt motive power during the past year. During this time, several Class 1 railroads have heavily adopted the rebuilding and modernization of existing motive power. The survey also looks at how the needs of the railroads are changing in terms of motive power both due to Precision Scheduled Railroading (PSR) and also due to the novel Coronavirus pandemic. Finally, this survey will conclude with a look back at the high horsepower race following the retirement of the EMD SD80MAC locomotives from Class 1 ownership.

scholarly journals The Role of Dental Professionals in Pandemic Events and Disaster Responses

2020 ◽  
pp. 1-5 ◽  
Author(s):  
Guangwen Li ◽  
Bei Chang ◽  
Hui Li ◽  
Rui Wang ◽  
Gang Li
Keyword(s):  
Human Resources ◽  
Emergency Response ◽  
Mass Casualties ◽  
The Novel ◽  
Public Health Emergencies ◽  
The Past ◽  
Emergency Responses ◽  
Novel Coronavirus ◽  
Dental Professionals

Abstract The past 20 years have seen major public health emergencies and natural disasters, including the Severe Acute Respiratory Syndrome outbreak caused by the SARS-associated coronavirus (SARS-CoV) in 2003; the Wenchuan earthquake in 2008; and the novel coronavirus pandemic (COVID-19) of 2019, which caused mass casualties, infections, and panic. These also resulted in complex demands for medical resources and information, and a shortage of human resources for emergency responses. To address the shortage of human resources required for these emergency responses, Chinese dental professionals made useful contributions. From this work, deficiencies in emergency response training and opportunities for the expansion of rescue capabilities were identified, and relevant recommendations made.

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