scholarly journals Temporal Patterns in the Evolutionary Genetic Distance of SARS-CoV-2 during the COVID-19 Pandemic

2022 ◽  
pp. 1-4
Author(s):  
Jingzhi Lou ◽  
Shi Zhao ◽  
Lirong Cao ◽  
Hong Zheng ◽  
Zigui Chen ◽  
...  
Keyword(s):  
Genetic Distance ◽  
Nonstructural Protein ◽  
Protein S ◽  
Genetic Distances ◽  
Spike Protein ◽  
Sequencing Data ◽  
Reading Frame ◽  
N Protein ◽  
Rdrp Region ◽  
Evolutionary Genetic

During coronavirus disease 2019 (COVID-19) pandemic, the genetic mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred frequently. Some mutations in the spike protein are considered to promote transmissibility of the virus, while the mutation patterns in other proteins are less studied and may also be important in understanding the characteristics of SARS-CoV-2. We used the sequencing data of SARS-CoV-2 strains in California to investigate the time-varying patterns of the evolutionary genetic distance. The accumulative genetic distances were quantified across different time periods and in different viral proteins. The increasing trends of genetic distance were observed in spike protein (S protein), the RNA-dependent RNA polymerase (RdRp) region and nonstructural protein 3 (nsp3) of open reading frame 1 (ORF1), and nucleocapsid protein (N protein). The genetic distances in ORF3a, ORF8, and nsp2 of ORF1 started to diverge from their original variants after September 2020. By contrast, mutations in other proteins appeared transiently, and no evident increasing trend was observed in the genetic distance to the original variants. This study presents distinct patterns of the SARS-CoV-2 mutations across multiple proteins from the aspect of genetic distance. Future investigation shall be conducted to study the effects of accumulative mutations on epidemics characteristics.

scholarly journals Temporal patterns in the evolutionary genetic distance of SARS-CoV-2 during the COVID-19 pandemic

2020 ◽  
Author(s):  
Jingzhi Lou ◽  
Shi Zhao ◽  
Lirong Cao ◽  
Zigui Chen ◽  
Renee WY Chan ◽  
...  
Keyword(s):  
Genetic Distance ◽  
Nucleocapsid Protein ◽  
Hamming Distance ◽  
Protein S ◽  
Genetic Mutations ◽  
Reading Frame ◽  
N Protein ◽  
Rdrp Region ◽  
Evolutionary Genetic ◽  
Increasing Trend

AbstractBackgroundDuring the pandemic of coronavirus disease 2019 (COVID-19), the genetic mutations occurred in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cumulatively or sporadically. In this study, we employed a computational approach to identify and trace the emerging patterns of the SARS-CoV-2 mutations, and quantify accumulative genetic distance across different periods and proteins.MethodsFull-length human SARS-CoV-2 strains in United Kingdom were collected. We investigated the temporal variation in the evolutionary genetic distance defined by the Hamming distance since the start of COVID-19 pandemic.FindingsOur results showed that the SARS-CoV-2 was in the process of continuous evolution, mainly involved in spike protein (S protein), the RNA-dependent RNA polymerase (RdRp) region of open reading frame 1 (ORF1) and nucleocapsid protein (N protein). By contrast, mutations in other proteins were sporadic and genetic distance to the initial sequenced strain did not show an increasing trend.

scholarly journals Epidemiological associations with genomic variation in SARS-CoV-2

2021 ◽  
Author(s):  
Ali Rahnavard ◽  
Rebecca Clement ◽  
Nathaniel Stearrett ◽  
Marcos Pérez-Losada ◽  
Keith A. Crandall ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Nonstructural Protein ◽  
Protein S ◽  
Disease Status ◽  
Virus Genome ◽  
Genomic Variation ◽  
Spike Protein ◽  
Genome Variation ◽  
Host Sex ◽  
Novel Coronavirus

Abstract The 2019 novel coronavirus (SARS-CoV-2) is the etiological agent of the COVID-19 pandemic and evolves to evade both host immune systems and intervention strategies. To diminish the short-term and long-term impacts of coronavirus (CoV), we investigated CoV differences at the nucleotide and protein level and CoV genomic variation associated with epidemiological variation and geography. We divided the CoV genome into 29 constituent regions for this analysis. Our results highlight the variation of CoV variants of lineage and show that nonstructural protein 3 (nsp3) and Spike protein (S) have the highest variation and greatest correlation with the viral whole-genome variation, which makes these two proteins potential targets for treatments. S protein variation is highly correlated with nsp3, nsp6, and 3'−to−5' exonuclease. Country of origin and time since the start of the pandemic were the most influential metadata in these differences. Host sex and age are the lowest in terms of explaining the virus genome variation. We quantified variation explained by regions of the CoV genome across different CoV viruses including, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), other severe acute respiratory syndrome coronavirus SARS-CoV (SARS-related), and bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses (Bat-SL-CoV). We found that Spike protein and nsp3 explain most of the variation among these viruses; they are also among the genomic regions with the highest number of sites under natural selection. Our results provide a direction to prioritize genes associated with outcome predictors, including health, therapeutic, and vaccine outcomes, and to inform improved DNA tests for predicting disease status.

SARS-CoV-2 proteins: Are they useful as targets for COVID-19 drugs and vaccines?

2021 ◽  
Vol 21 ◽  
Author(s):  
Mohammed Elimam Ahamed Mohammed
Keyword(s):  
Lipid Bilayer ◽  
Drug Targets ◽  
Protein S ◽  
Bilayer Membrane ◽  
Viral Envelope ◽  
Host Cells ◽  
Spike Protein ◽  
Structural Proteins ◽  
Accessory Proteins ◽  
N Protein

: The proteins of coronavirus are classified to nonstructural, structural, and accessory. There are 16 nonstructural viral proteins beside their precursors (1a and 1ab polyproteins). The nonstructural proteins are named as nsp1 to nsp16 and they act as enzymes, coenzymes, and binding proteins to facilitate the replication, transcription, and translation of the virus. The structural proteins are bound to the RNA in the nucleocapsid (N- protein) or to the lipid bilayer membrane of the viral envelope. The lipid bilayer proteins include the membrane protein (M), envelope protein (E), and spike protein (S). Beside their role as structural proteins, they are essential for the host cells binding and invasion. The SARS-CoV-2 contains six accessory proteins which participates in the viral replication, assembly and virus- host interactions. The SARS-CoV-2 accessory proteins are orf3a, orf6, orf7a, orf7b, orf8, and orf10. The functions of the SARS-CoV-2 are not well known, while the functions of their corresponding proteins in SARS-CoV are either well known or poorly studied. Recently, the Oxford University and Pfizer and BioNTech made SARS-CoV-2 vaccines through targeting the spike protein gene. The US Food and Drug Administration (FDA) and the health authorities of the United Kingdom approved and started vaccination using the Pfizer and BioNTech mRNA vaccine. Also, The FDA of USA approved the treatment of COVID-19 using two monoclonal antibodies produced by Regeneron pharmaceuticals to target the spike protein. The SARS-CoV-2 proteins can be used for the diagnosis, as drug targets and in vaccination trials for COVID-19. For future COVID-19 research, more efforts should be done to elaborate the functions and structure of the SARS-CoV-2 proteins so as to use them as targets for COVID-19 drug and vaccines. Special attention should be drawn to extensive research on the SARS-CoV-2 nsp3, orf8, and orf10.

scholarly journals Ubiquitous genomic fragment in human 2019-nCoV viruses in the spike-protein, also encoding a novel 87 aa protein, completely missing in all other coronaviruses

2020 ◽  
Author(s):  
Sandeep Chakraborty
Keyword(s):  
Viral Entry ◽  
Host Cells ◽  
Spike Protein ◽  
Genomic Fragment ◽  
Sequencing Data ◽  
Epitope Region ◽  
Reading Frame ◽  
Spike Gene ◽  
And Function ◽  
Highly Virulent

The origins of the highly virulent coronavirus isolated from Wuhan (Hubei, China) are uncertain, as are the reasons for its highly virulent nature (human-to-human transmission before the onset of symptoms). Here, 29 genomes of 2019-nCoV in GISAID reveals a genomic fragment which is present in all 2019-nCoV genomes, (and also in the recent Nanopore sequencing data from a family [1]), and absent in other species. The only entry in GISAID from bats (BatCoV-RaTG13) is a mystery (it does not have any publications linked to it), but is very close to human 2019-nCoV. Mutations in the viral genome need to translate in changes in protein sequences (and function) in order modulate its virulence. This genomic fragment is in the N-terminal of the spike-protein (98-228), a known-epitope region and implicated in viral entry into host cells. Interestingly, this region also encodes a novel 87 novel protein, with a shifted open-reading frame (a phenomenon common in viruses). The genomic fragment will help in faster diagnosis (excluding all other coronaviruses), while the protein information will aid in vaccine or inhibitor design. Note, there are no other fragments which have this property - present in nCov and absent in others. Coincidentally, amino acids ‘17-240 were deleted from the N-terminal domain of the TGEV Spike gene’ using CRISPR, an experiment carried out in Wuhan [2].

Discovery of Some Antiviral Natural products to fight against Novel Corona Virus (SARS-CoV-2) using Insilico approach

2020 ◽  
Vol 23 ◽  
Author(s):  
Ashish Shah ◽  
Vaishali Patel ◽  
Bhumika Parmar
Keyword(s):  
Binding Affinity ◽  
Protein S ◽  
Docking Studies ◽  
Spike Protein ◽  
Enveloped Viruses ◽  
Bioactivity Prediction ◽  
Corona Virus ◽  
Main Protease ◽  
Antiviral Activities ◽  
Deadly Disease

Background: Novel Corona virus is a type of enveloped viruses with a single stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. Objective: We had selected 30 phytoconstituents from the different plants which are reported for antiviral activities against corona virus (CoVs) and performed insilico screening to find out phytoconstituents which have potency to inhibit specific target of novel corona virus. Methods: We had perform molecular docking studies on three different proteins of novel corona virus namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. Results: We had screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin using insilico approach. All compounds found safe in insilico toxicity studies. Bioactivity prediction reviles that these all compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had higher binding affinity for the target PLpro and Spike protein. Conclusion: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

scholarly journals SARS-CoV-2 Nucleocapsid Protein Targets RIG-I-Like Receptor Pathways to Inhibit the Induction of Interferon Response

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 530
Author(s):  
Soo Jin Oh ◽  
Ok Sarah Shin
Keyword(s):  
Nucleocapsid Protein ◽  
Nuclear Translocation ◽  
Nonstructural Protein ◽  
Poly I:C ◽  
Interferon Response ◽  
Type I ◽  
Antiviral Immune Response ◽  
N Protein ◽  
Nonstructural Protein 1 ◽  
Polycytidylic Acid

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) that has resulted in the current pandemic. The lack of highly efficacious antiviral drugs that can manage this ongoing global emergency gives urgency to establishing a comprehensive understanding of the molecular pathogenesis of SARS-CoV-2. We characterized the role of the nucleocapsid protein (N) of SARS-CoV-2 in modulating antiviral immunity. Overexpression of SARS-CoV-2 N resulted in the attenuation of retinoic acid inducible gene-I (RIG-I)-like receptor-mediated interferon (IFN) production and IFN-induced gene expression. Similar to the SARS-CoV-1 N protein, SARS-CoV-2 N suppressed the interaction between tripartate motif protein 25 (TRIM25) and RIG-I. Furthermore, SARS-CoV-2 N inhibited polyinosinic: polycytidylic acid [poly(I:C)]-mediated IFN signaling at the level of Tank-binding kinase 1 (TBK1) and interfered with the association between TBK1 and interferon regulatory factor 3 (IRF3), subsequently preventing the nuclear translocation of IRF3. We further found that both type I and III IFN production induced by either the influenza virus lacking the nonstructural protein 1 or the Zika virus were suppressed by the SARS-CoV-2 N protein. Our findings provide insights into the molecular function of the SARS-CoV-2 N protein with respect to counteracting the host antiviral immune response.

scholarly journals Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 821
Author(s):  
Rohitash Yadav ◽  
Jitendra Kumar Chaudhary ◽  
Neeraj Jain ◽  
Pankaj Kumar Chaudhary ◽  
Supriya Khanra ◽  
...  
Keyword(s):  
Host Cell ◽  
Protein S ◽  
Structural Similarity ◽  
Cell Receptor ◽  
Molecular Assembly ◽  
The Body ◽  
Spike Protein ◽  
Structural Proteins ◽  
Structural Protein ◽  
Novel Coronavirus

Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) of around 26 to 32 kilobases, and has been known to cause infection to a myriad of mammalian hosts, such as humans, cats, bats, civets, dogs, and camels with varied consequences in terms of death and debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and found to be the causative agent of coronavirus disease-19 (COVID-19), shows 88% of sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21, 79% with SARS-CoV and 50% with MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between the receptor binding domain (RBD) of spike protein (S) of SARS-CoV-2 and SARS-CoV. During infection, spike protein of SARS-CoV-2 compared to SARS-CoV displays 10–20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage of S protein by transmembrane protease serine 2 (TMPRSS2). Following cellular entry, the ORF-1a and ORF-1ab, located downstream to 5′ end of + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a and pp1ab. These polyproteins, following protease-induced cleavage and molecular assembly, form functional viral RNA polymerase, also referred to as replicase. Thereafter, uninterrupted orchestrated replication-transcription molecular events lead to the synthesis of multiple nested sets of subgenomic mRNAs (sgRNAs), which are finally translated to several structural and accessory proteins participating in structure formation and various molecular functions of virus, respectively. These multiple structural proteins assemble and encapsulate genomic RNA (gRNA), resulting in numerous viral progenies, which eventually exit the host cell, and spread infection to rest of the body. In this review, we primarily focus on genomic organization, structural and non-structural protein components, and potential prospective molecular targets for development of therapeutic drugs, convalescent plasm therapy, and a myriad of potential vaccines to tackle SARS-CoV-2 infection.

scholarly journals Genetic Variation Among Colletotrichum graminicola Isolates from Four Hosts Using Isozyme Analysis

Plant Disease ◽  
2004 ◽  
Vol 88 (4) ◽  
pp. 402-406 ◽  
Author(s):  
B. J. Horvath ◽  
J. M. Vargas
Keyword(s):  
Genetic Variation ◽  
Genetic Distance ◽  
Geographic Origin ◽  
Creeping Bentgrass ◽  
Genetic Distances ◽  
Colletotrichum Graminicola ◽  
Annual Bluegrass ◽  
Close Relationship ◽  
Host Origin ◽  
Serious Disease

Anthracnose basal rot (ABR) is a serious disease of turfgrasses that is caused by the pathogen Colletotrichum graminicola. The relationships of isolates causing ABR on turfgrasses to those causing disease on important crop hosts (maize, sorghum) remain unresolved. Genetic variation among isolates from annual bluegrass, creeping bentgrass, maize, and sorghum was evaluated based on host origin and geographic origin. Isozymes were used to estimate the genetic variation of the isolates. Five enzyme systems comprising 16 alleles from 5 loci were used. Allele frequencies, genetic distance, and linkage disequilibrium values were calculated for isolates based on both host and geographic origin. Isolates from creeping bentgrass and annual bluegrass were the most closely related based on Nei's genetic distance, while isolates from maize and sorghum were the most distantly related, consistent with their known species-level relationship. Isolates from annual bluegrass and creeping bentgrass had different genetic distances to isolates from both maize and sorghum. Annual bluegrass isolates from different geographic regions had the smallest genetic distance values observed in this study, indicating a very close relationship regardless of geographic origin. Based on these data, it appears that host origin, not geographic origin, plays a more important role in the genetic diversity of these fungi.

Ampelographic characterization of white grapevine cul-tivars (Vitis vinifera L.) grown in Palestine

2015 ◽  
Vol 3 (1) ◽  
pp. 1-11
Author(s):  
Rezq Basheer-Salimia
Keyword(s):  
Genetic Diversity ◽  
Genetic Distance ◽  
Germplasm Conservation ◽  
Genetic Distances ◽  
Vitis Vinifera L ◽  
Similarity Matrix ◽  
Breeding Programs ◽  
Local Varieties ◽  
Synonymies And Homonymies

Abstract: In Palestine, grape culture consists of ecotypes and cultivars (also called local varieties), for which a large number of homonymous and synonymous designations exist as well as misnaming of cultivars. The present study is the first report using detailed ampelographic characterizations (39 informative traits) to assess genetic diversity and detect similarities among sixteen accessions collected from putative diverse grape genotypes In general, 30 descriptors presented highly and satisfactory divergent genotypes, whereas the remaining traits showed no or very little ampelographic variation. Based on the similarity matrix and the resulting dendrogram of these ampelographic data, distinguishable genotypes as well as some cases of synonymies and homonymies clearly exist. A synonymy case seemed to be in four genotypes including Jandali-Mfarad, Jan-dali-Mrazraz, Jandali, and Hamadani-Mattar, which indeed showed genetic distances of less than 0.5, sug-gesting their relatedness, and the possibility that they are the same genotype, but with different names. In addition, homonym cases also occur in the following pairs of “Marawi’s, Hamadani’s, and Zaini’s genotypes, in which each pair seems to be two distinctive genotypes. Finally, among the 16 examined genotypes, the Zaini-Baladi genotype tended to show the highest genetic distance values from the others and thus could be potentially incorporated into any further local or regional breeding programs as well as germplasm conservation.

scholarly journals The optimal mating distance resulting from heterosis and genetic incompatibility

2018 ◽  
Vol 4 (11) ◽  
pp. eaau5518 ◽  
Author(s):  
Xinzhu Wei ◽  
Jianzhi Zhang
Keyword(s):  
Animal Model ◽  
Genetic Distance ◽  
Polynomial Function ◽  
Genetic Distances ◽  
Quadratic Polynomial ◽  
Model Organisms ◽  
Genetic Incompatibility ◽  
Large Numbers ◽  
Practical Implications

Theory predicts that the fitness of an individual is maximized when the genetic distance between its parents (i.e., mating distance) is neither too small nor too large. However, decades of research have generally failed to validate this prediction or identify the optimal mating distance (OMD). Respectively analyzing large numbers of crosses of fungal, plant, and animal model organisms, we indeed find the hybrid phenotypic value a humped quadratic polynomial function of the mating distance for the vast majority of fitness-related traits examined, with different traits of the same species exhibiting similar OMDs. OMDs are generally slightly greater than the nucleotide diversities of the species concerned but smaller than the observed maximal intraspecific genetic distances. Hence, the benefit of heterosis is at least partially offset by the harm of genetic incompatibility even within species. These results have multiple theoretical and practical implications for speciation, conservation, and agriculture.

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