scholarly journals Emerging Strains Of SARS-Cov2 And Their Inhibition by The Use of Phytochemicals: An In-Silico Analysis

2021 ◽  
Author(s):  
Mohammad Faheem Khan ◽  
Tanveer Ahamad ◽  
Waseem Ahmad Ansari ◽  
Mohsin Ali Khan ◽  
Zaw Ali Khan ◽  
...  
Keyword(s):  
Rna Virus ◽  
In Silico Analysis ◽  
Open Reading Frames ◽  
Host Cells ◽  
Structural Proteins ◽  
Angiotensin Converting Enzyme 2 ◽  
A Genome ◽  
Infectivity Rate ◽  
Silico Analysis ◽  
Prime Target

Abstract Recently identified coronavirus namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded positive-sense RNA virus with a genome of 29.9 kb in size encoding 14 open reading frames (ORFs) and 27 different structural and non-structural proteins. Among the structural proteins, trimeric-shaped spike glycoprotein is responsible for the entry of the SARS-CoV2 genome into host cells by interacting with human angiotensin-converting enzyme 2 (ACE2) receptors that are present on the cell surface with high affinity. Notably, inhibition of spike protein is considered a prime target for the development of drugs against COVID-19. Viruses can mutate, and SARS-CoV-2 is no exception. Since the first whole genome of SARS-CoV2 was published in February 2020, at least 4400 amino acid substitutions and several thousand mutations have been identified to date. As of today, more than 3500 new variants of SARS-CoV2 have been sequenced with a high spreading and infectivity rate which makes the virus more contagious. These new variants have been spread to several countries including United States (US), United Kingdom (UK), Brazil, South Africa, India, and other countries, etc. Therefore, herein, we analysed the new SARS-CoV2 strains, constructed the 3D homology models of Brazil P.1 and Indian B.1.617 variants, and screened them against 100 phytochemicals having previously identified anti-viral activity. Our study revealed that the top three phytochemicals for each of the new strains might serve as potential anti- SARS-CoV-2 agents for further drug discovery and development process to tackle COVID-19.

scholarly journals Structural Dissection of Viral Spike-Protein Binding of SARS-CoV-2 and SARS-CoV-1 to the Human Angiotensin-Converting Enzyme 2 (ACE2) as Cellular Receptor

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1038
Author(s):  
Deborah Giordano ◽  
Luigi De Masi ◽  
Maria Antonia Argenio ◽  
Angelo Facchiano
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico Analysis ◽  
Host Cells ◽  
Spike Protein ◽  
Cellular Receptor ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
The World ◽  
Silico Analysis

An outbreak by a new severe acute respiratory syndrome betacoronavirus (SARS-CoV-2) has spread CoronaVirus Disease 2019 (COVID-19) all over the world. Immediately, following studies have confirmed the human Angiotensin-Converting Enzyme 2 (ACE2) as a cellular receptor of viral Spike-Protein (Sp) that mediates the CoV-2 invasion into the pulmonary host cells. Here, we compared the molecular interactions of the viral Sp from previous SARS-CoV-1 of 2002 and SARS-CoV-2 with the host ACE2 protein by in silico analysis of the available experimental structures of Sp-ACE2 complexes. The K417 amino acid residue, located in the region of Sp Receptor-Binding Domain (RBD) of the new coronavirus SARS-CoV-2, showed to have a key role for the binding to the ACE2 N-terminal region. The R426 residue of SARS-CoV-1 Sp-RBD also plays a key role, although by interacting with the central region of the ACE2 sequence. Therefore, our study evidenced peculiarities in the interactions of the two Sp-ACE2 complexes. Our outcomes were consistent with previously reported mutagenesis studies on SARS-CoV-1 and support the idea that a new and different RBD was acquired by SARS-CoV-2. These results have interesting implications and suggest further investigations.

scholarly journals Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins

2020 ◽  
Author(s):  
Souradip Basu ◽  
Suparba Mukhopadhyay ◽  
Rajdeep Das ◽  
Sarmishta Mukhopadhyay ◽  
Pankaj Kumar Singh ◽  
...  
Keyword(s):  
Negative Impact ◽  
Rna Virus ◽  
Open Reading Frames ◽  
Structural Proteins ◽  
Pharmacological Intervention ◽  
Mutant Proteins ◽  
Worldwide Population ◽  
A Genome ◽  
Pathogenesis Related ◽  
Related Proteins

AbstractThe SARS-CoV-2 is a positive stranded RNA virus with a genome size of ~29.9 kilobase pairs which spans 29 open reading frames. Studies have revealed that the genome encodes about 16 non-structural proteins (nsp), four structural proteins, and six or seven accessory proteins. Based on prevalent knowledge on SARS-CoV and other coronaviruses, functions have been assigned for majority of the proteins. While, researchers across the globe are engrossed in identifying a potential pharmacological intervention to control the viral outbreak, none of the work has come up with new antiviral drugs or vaccines yet. One possible approach that has shown some positive results is by treating infected patients with the plasma collected from convalescent COVID-19 patients. Several vaccines around the world have entered their final trial phase in humans and we expect that these will in time be available for application to worldwide population to combat the disease. In this work we analyse the effect of prevalent mutations in the major pathogenesis related proteins of SARS-COV2 and attempt to pinpoint the effects of those mutations on the structural stability of the proteins. Our observations and analysis direct us to identify that all the major mutations have a negative impact in context of stability of the viral proteins under study and the mutant proteins suffer both structural and functional alterations as a result of the mutations. Our binary scoring scheme identifies L84S mutation in ORF8 as the most disruptive of the mutations under study. We believe that, the virus is under the influence of an evolutionary phenomenon similar to Muller’s ratchet where the continuous accumulation of these mutations is making the virus less virulent which may also explain the reduction in fatality rates worldwide.

scholarly journals The Novel Agrotis ipsilon Nora Virus Confers Deleterious Effects to the Fitness of Spodoptera frugiperda (Lepidoptera: Noctuidae)

2021 ◽  
Vol 12 ◽  
Author(s):  
Tong Li ◽  
Ruobing Guan ◽  
Yuqing Wu ◽  
Su Chen ◽  
Guohui Yuan ◽  
...  
Keyword(s):  
Spodoptera Frugiperda ◽  
Rna Virus ◽  
Open Reading Frames ◽  
Agrotis Ipsilon ◽  
The Novel ◽  
Black Cutworm ◽  
A Genome ◽  
Nora Virus ◽  
Novel Host ◽  
Lepidoptera Noctuidae

In the present study, we identified a novel, positive-sense single-stranded RNA virus in the Chinese black cutworm, Agrotis ipsilon. It has a genome length of 11,312 nucleotides, excluding the poly(A) tails, and contains five open reading frames. The ORF2 encodes the conserved domains of RNA helicase and RNA-dependent RNA polymerase, while ORF4 and 5 encode three viral proteins. Herein, the A. ipsilon virus was clustered with a Helicoverpa armigera Nora virus and was thus provisionally named “Agrotis ipsilon Nora virus” (AINV). AINV was successfully transmitted into a novel host, Spodoptera frugiperda, through injection, causing a stable infection. This found the possibility of horizontal AINV transmission among moths belonging to the same taxonomic family. Nonetheless, AINV infection was deleterious to S. frugiperda and mainly mediated by antiviral and amino acid metabolism-related pathways. Furthermore, the infection significantly increased the S. frugiperda larval period but significantly reduced its moth eclosion rate. It suggests that AINV is probably to be a parasitic virus of S. frugiperda.

scholarly journals Identification of Novel Hypothalamic MicroRNAs as Promising Therapeutics for SARS-CoV-2 by Regulating ACE2 and TMPRSS2 Expression: An In Silico Analysis

2020 ◽  
Vol 10 (10) ◽  
pp. 666
Author(s):  
Debasmita Mukhopadhyay ◽  
Bashair M. Mussa
Keyword(s):  
In Silico ◽  
Binding Capacity ◽  
Therapeutic Targets ◽  
In Silico Analysis ◽  
Neurological Impairment ◽  
Essential Elements ◽  
Cell Entry ◽  
Angiotensin Converting Enzyme 2 ◽  
Transmembrane Serine Protease ◽  
Silico Analysis

Background: Neuroinvasion of severe acute respiratory syndrome coronavirus (SARS-CoV) is well documented and, given the similarities between this virus and SARS-CoV-2, it seems that the neurological impairment that is associated with coronavirus disease 2019 (COVID-19) is due to SARS-CoV-2 neuroinvasion. Hypothalamic circuits are exposed to the entry of the virus via the olfactory bulb and interact centrally with crucial respiratory nuclei. Hypothalamic microRNAs are considered as potential biomarkers and modulators for various diseases and future therapeutic targets. The present study aims to investigate the microRNAs that regulate the expression of hypothalamic angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential elements for SARS-CoV-2 cell entry. Methods: To determine potential hypothalamic miRNAs that can directly bind to ACE2 and TMPRSS2, multiple target bioinformatics prediction algorithms were used, including miRBase, Target scan, and miRWalk2.029. Results: Our in silico analysis has revealed that, although there are over 5000 hypothalamic miRNAs, around 31 miRNAs and 29 miRNAs have shown binding sites and strong binding capacity against ACE2 and TMPRSS2, respectively. Conclusion: These novel potential hypothalamic miRNAs can be used to identify new therapeutic targets to treat neurological symptoms in COVID-19 patients via regulation of ACE2 and TMPRSS2 expression.

scholarly journals Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Joseph Thomas Ortega ◽  
Beata Jastrzebska ◽  
Hector Rafael Rangel
Keyword(s):  
Free Energy ◽  
Electrostatic Interactions ◽  
Structural Model ◽  
Binding Free Energy ◽  
In Silico Analysis ◽  
Spike Protein ◽  
Medical Community ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Silico Analysis

The rise of SARS-CoV-2 variants, with changes that could be related to an increased virus pathogenicity, have received the interest of the scientific and medical community. In this study, we evaluated the changes that occurred in the viral spike of the SARS-CoV-2 Omicron variant and whether these changes modulate the interactions with the angiotensin-converting enzyme 2 (ACE2) host receptor. The mutations associated with the Omicron variant were retrieved from the GISAID and covariants.org databases, and a structural model was built using the SWISS-Model server. The interaction between the spike and the human ACE2 was evaluated using two different docking software, Zdock and Haddock. We found that the binding free energy was lower for the Omicron variant as compared to the WT spike. In addition, the Omicron spike protein showed an increased number of electrostatic interactions with ACE2 than the WT spike, especially the interactions related to charged residues. This study contributes to a better understanding of the changes in the interaction between the Omicron spike and the human host ACE2 receptor.

scholarly journals Phages from Genus Bruynoghevirus and Phage Therapy: Pseudomonas Phage Delta Case

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1965
Author(s):  
Petar Knezevic ◽  
Aleksandra Petrovic Fabijan ◽  
Damir Gavric ◽  
Jovana Pejic ◽  
Zsolt Doffkay ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Phage Therapy ◽  
In Silico Analysis ◽  
Bacterial Toxin ◽  
Broad Host Range ◽  
Multiplicity Of Infection ◽  
Promising Candidate ◽  
A Genome ◽  
Silico Analysis

The applicability and safety of bacteriophage Delta as a potential anti-Pseudomonas aeruginosa agent belonging to genus Bruynoghevirus (family Podoviridae) was characterised. Phage Delta belongs to the species Pseudomonas virus PaP3, which has been described as a temperate, with cos sites at the end of the genome. The phage Delta possesses a genome of 45,970 bp that encodes tRNA for proline (Pro), aspartic acid (Asp) and asparagine (Asn) and does not encode any known protein involved in lysogeny formation or persistence. Analysis showed that phage Delta has 182 bp direct terminal repeats at the end of genome and lysogeny was confirmed, neither upon infection at low nor at high multiplicity of infection (MOI). The turbid plaques that appear on certain host lawns can result from bacteriophage insensitive mutants that occur with higher frequency (10−4). In silico analysis showed that the genome of Delta phage does not encode any known bacterial toxin or virulence factor, determinants of antibiotic resistance and known human allergens. Based on the broad host range and high lytic activity against planktonic and biofilm cells, phage Delta represents a promising candidate for phage therapy.

scholarly journals A Review on the Novel Coronavirus Disease based on In-silico Analysis of Various Drugs and Target Proteins

2020 ◽  
Vol 14 (suppl 1) ◽  
pp. 849-860
Author(s):  
Gauravi N. Trivedi ◽  
Janhavi T. Karlekar ◽  
Hiren A. Dhameliya ◽  
Hetalkumar Panchal
Keyword(s):  
In Silico ◽  
Close Contact ◽  
Genome Structure ◽  
In Silico Analysis ◽  
Bioactive Compound ◽  
Host Cells ◽  
World Health ◽  
Large Set ◽  
Genomic Rnas ◽  
Silico Analysis

Coronavirus Disease (COVID-19) is a new disease that emerged in Wuhan, China which spreads through close contact of people, often by small droplets produced during coughing or sneezing. Detail mechanism by which it spreads between people are under investigation. The World Health Organization (WHO) declared this disease as a pandemic after the severity of the disease increased. Many scientific reports gathered have suggested many drugs that could be potential candidates for the treatment. Although, clinical effectiveness has not been fully evaluated. In this review, we have aggregated the data from few research articles, official news websites and few review papers regarding its phylogenetic relation, genomic constitution, transmission, replication and in-silico analysis done by researchers for few potent drugs that are currently used to cure COVID-19. SARS-CoV-2 belongs to Betacoronavirus genus with Genome structure consists 14 Open Reading Frames (ORFs) that encode 27 proteins. Coronavirus replicates into the host cells having unique mechanisms like ribosome frame-shifting and synthesis of genomic and sub genomic RNAs. In-silico methods have the advantage that they can make fast predictions for a large set of compounds in a high-throughput mode and also make their prediction based on the structure of a compound even before it has been synthesized. In-silico softwares have been used to find or to improve a novel bioactive compound, which may exhibit a strong affinity to a particular target in the drug development process.

scholarly journals Identification of Francisella tularensis Genes Affected by Iron Limitation

2006 ◽  
Vol 74 (7) ◽  
pp. 4224-4236 ◽  
Author(s):  
Kaiping Deng ◽  
Robert J. Blick ◽  
Wei Liu ◽  
Eric J. Hansen
Keyword(s):  
In Silico Analysis ◽  
Growth Conditions ◽  
Open Reading Frames ◽  
Untranslated Regions ◽  
Spectrometric Analysis ◽  
Live Vaccine Strain ◽  
Feeding Experiment ◽  
Wild Type ◽  
Silico Analysis ◽  
Reading Frames

ABSTRACT Cells of an attenuated live vaccine strain (LVS) of F. tularensis grown under iron-restricted conditions were found to contain increased quantities of several proteins relative to cells of this same strain grown under iron-replete conditions. Mass spectrometric analysis identified two of these proteins as IglC and PdpB, both of which are encoded by genes located in a previously identified pathogenicity island in F. tularensis LVS. Regions with homology to the consensus Fur box sequence were located immediately in front of the iglC and pdpB open reading frames (ORFs), and in silico analysis of the F. tularensis Schu4 genome detected a number of predicted 5′ untranslated regions that contained putative Fur boxes. The putative Fur box preceding Francisella iron-regulated gene A (figA) had the highest degree of identity with the consensus Fur box sequence. DNA microarray analysis showed that nearly 80 of the genes in the F. tularensis LVS genome were up- or down-regulated at least twofold under iron-restricted growth conditions. When tested for possible siderophore production by means of the Chrome Azurol S assay, a wild-type F. novicida strain produced a large reaction zone whereas its figA mutant produced very little reactivity in this assay. In addition, a cross-feeding experiment demonstrated that this siderophore-like activity produced by the wild-type F. novicida strain could enhance the ability of the F. novicida figA mutant to grow under iron-restricted conditions. This study provides the first identification of iron-regulated genes in F. tularensis LVS and evidence for the production of a siderophore-like molecule by F. novicida.

scholarly journals Diabetes mellitus augments the complications of patients with COVID-19: a review

2020 ◽  
Vol 8 (7) ◽  
pp. 2716
Author(s):  
Parthiba Pramanik ◽  
Purushottam Pramanik
Keyword(s):  
Diabetes Mellitus ◽  
Severe Acute Respiratory Syndrome ◽  
Virus Disease ◽  
Rna Virus ◽  
Renin Angiotensin System ◽  
Acute Effect ◽  
Host Cells ◽  
Diabetic Patients ◽  
Angiotensin Converting Enzyme 2 ◽  
Appropriate Therapy

Corona virus disease 2019 (COVID-19) is current pandemic infection caused by RNA virus named severe acute respiratory syndrome coronavirus-2 (SARS Cov-2). The lungs are the organs most affected by COVID-19 and people were died due to severe acute respiratory s syndrome, pneumonia and multi-organs failure. Fatality rate was more, those who suffer in chronic diseases including diabetes mellitus (DM). As COVID-19 pandemic is accelerating , it is important to understand the molecular mechanism through which DM increases the severity related to COVID-19 to able to design more appropriate therapy. The aims of this study was to identify mechanisms through re-analysis of publicly available data by which DM increases susceptibility for COVID-19 infection and/or increase complication for SARS-Cov-2 infection. SARS Cov-2 accesses host cells via membrane bound enzyme, angiotensin converting enzyme-2 (ACE2). This leads to imbalance of vasoprotective and vasodeletorious arms of renin angiotensin system (RAS) with over activity of vasodeletorious arms. Such imbalance of RAS induces alveolar damage, flooding the alveoli and difficulty in breathing. DM augmented the chance of pulmonary infection by impairment of innate immunity and down regulation of ACE2. Hence, diabetic patients of COVID-19 die from multi-organ failure, shock, heart failure, arrhythmias and renal failure along with severe acute respiratory syndrome. Thus it is concluded that DM augments the complications from COVID-19 by enhancing development of RAS imbalance. From view point of public health it is suggested to keep the lung healthy, maintain blood glucose level properly, and intake foods rich in antioxidant and anti-inflammatory agents to prevent and ameliorate the acute effect of COVID-19 in diabetic patients.

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