scholarly journals Witnessing Evolution of SARS-CoV-2 through Comparative Phylogenomics: The Proximate Origin is Guangdong, not Wuhan

2020 ◽  
Author(s):  
Özgül Doğan ◽  
Ertan Mahir Korkmaz ◽  
Mahir Budak ◽  
Battal Çıplak ◽  
Hasan Hüseyin Başıbüyük
Keyword(s):  
Exponential Growth ◽  
Viral Genome ◽  
Doubling Time ◽  
Rna Viruses ◽  
Amino Acid Sequences ◽  
Viral Population ◽  
N Gene ◽  
Pandemic Strain ◽  
Synonymous Mutations ◽  
S Gene

A new form of coronavirus called severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) is currently causing a pandemic. A six-month evolutionary history of SARS-CoV-2 is witnessed by characterising the total genome of 821 samples using comparative phylogenomic approaches. Our analyses produced striking inclusive results that may guide scientists/professionals for the past/future of pandemic. Phylogenetic and time estimation analyses suggest the proximate origin of pandemic strain as Guangdong and the origin time as first half of September 2019, not Wuhan and December 2019, respectively. The viral genome experienced a substitution rate similar to other RNA viruses, but it is particularly high in some of the peptides encoding sequences such as leader protein, E gene, orf8, orf10, nsp10, N gene, S gene and M gene and nsp4, while low in nsp11, orf7a, 3C-like proteinase, nsp9, nsp8 and endoRNase. Most strikingly, the divergence rate of amino acid sequences is high proportional to nucleotide divergence. Additionally, specific non-synonymous mutations in nsp3 and nsp6 evolved under positive selection. The exponential growth rate (r), doubling time (Td) and R0 were estimated to be 47.43 per year, 5.39 days and 2.72, respectively. Comparison of synapomorphies distinguishing the SARS-CoV-2 and the candidate ancestor bat coronavirus indicates that mutation pattern in nsp3 and S gene enabled the new strain to invade human and become a pandemic strain. We arrive at the following main conclusions: (i) six months evolution of viral genome is nearly neutral, (ii) origin of pandemic is not Wuhan and predates formal reports, (iii) although viral population is ongoing an exponential growth, the doubling time is evolving towards shortening, and (iv) divergence rate of total genome is similar to other RNA viruses, but it is prominently high in some genes while low in some others and evolution in these genes should be closely monitored as their protein products intervening to pathogenicity, virulence and immune response.

scholarly journals Bayesian phylodynamic inferences on the temporal evolution and global transmission of SARS-CoV-2

2020 ◽  
Author(s):  
Jianguo Li ◽  
Zhen Li ◽  
Xiaogang Cui ◽  
Changxin Wu
Keyword(s):  
Viral Genome ◽  
Viral Population ◽  
Recent Common Ancestor ◽  
Replication Capacity ◽  
Synonymous Mutations ◽  
Most Recent Common Ancestor ◽  
The Usa ◽  
Bottle Neck ◽  
Clade 1 ◽  
The Uk

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely from China to the world. Although the viral genome has been well characterized, the evolutionary origin and global transmission dynamics of SARS-CoV-2 remain poorly investigated. To address this, we retrieved 313 SARS-CoV-2 genomes from the GISAID database (https://www.gisaid.org), from which 99 genomes generated from original clinical specimens with exact collection dates from 16 countries were selected and enrolled for Bayesian phylodynamic analysis. Here we show that the time to the Most Recent Common Ancestor (tMRCA) of SARS-CoV-2 is Dec 11, 2019 (95%HPD, Nov 21 - Dec 24). Two clades of global circulating strains of SARS-CoV-2 were suggested by Bayesian Maximum Clade Credibility (MCC) tree. The USA circulating strains of SARS-CoV-2 seemed to be from both of the two clades, the UK and Australia circulating strains were from Clade 1, the circulating strains in Singapore, Japan, Germany, France, and Italy were from Clade 2. Although we have not found any obvious bottle-neck-effect from the Bayesian Skyline Plot of the viral population dynamics reconstruction, a sharp reduction of the lower 95% HPD of the relative genetic diversity was observed from Feb 5, 2020, suggesting a possible initiation of a bottle-neck-effect. Thirteen (6 synonymous and 7 non-synonymous) mutations in the viral genome were observed, including two clade-specific mutations (C8782T and T1844C in Clade 1 rather than Clade 2) and eleven sub-clade specific mutations. All of the observed mutations occurred in the USA circulating strains, except one mutation T18488C only occurred in the UK circulating strains. A non-synonymous mutation in the 3’-UTR was also observed, suggesting an altered RNA replication capacity of SARS-CoV-2. We thus came to the conclusion that continuous evolution occurred in almost all regions of the SARS-CoV-2 genome and potentially in a country-specific manner. Further efforts on monitoring the genomic mutations of SARS-CoV-2 from different countries are recommended.

Phylogeny of 2019-nCoVs and SARS-like CoVs of Human, Bat and Pangolin Origin

2020 ◽  
Keyword(s):  
N Gene ◽  
Whole Genome ◽  
Human Origin ◽  
Gene Sequences ◽  
M Gene ◽  
S Gene ◽  
Shared Identity ◽  
Novel Coronavirus ◽  
S Genes

A novel coronavirus first broke out in Wuhan, China in December, 2019 has been declared a pandemic by WHO on March, 2020. This work aimed to search for probable ancestor of the virus, phylogeny of 2019-nCoVs and similar SL-CoVs based on the whole genome, M, N, ORF1ab, orf3a, and S gene sequences (n=84) obtained from GenBank using BLASTn software in the NCBI was done. Nucleotides of ORF3a and S-genes among 2019-nCoVs are identical, whereas its similar on the whole genome (99.9-100%), M-gene (99.7-100%), N-gene (99.9-100%) and ORF1ab-gene (99.7-100%). nCoVs are similar to bat CoV/RaTG13 on the whole genome (96.2%), M-gene (95.0%), N-gene (97%), ORF1ab-gene (95.3%), ORF3a-gene (99.1%) and S-gene (90.7%). Likewise, nCoVs exhibited homology to bat-CoVZXC21 on M-gene (93.2%), N-gene (91.5%), ORF1ab-gene (93.1%) and ORF3a-gene (94.4%). The emergent viruses shared identity to bat-CoVZC45 on N-gene (91.3%), ORF1ab-gene (92.8%) and ORF3a-gene (94.0%). In addition, pangolin-CoV/MP789 exhibited common sequences on M-gene (91.0%), N-gene (96.3%) and ORF3a-gene (93.3%) to nCoV. Furthermore, pangolin-CoV/MP789 is analogous to bat CoV/RaTG13 (91.3%) and bat-SL-CoVZXC21 (92.2%) on M-gene and to bat CoV/RaTG13 (94.8%) on N-gene. Nevertheless, nCoVs are distinct from the previously identified SL-CoVs of human origin. The present analysis indicates that nCoVs may have transmitted from bats, pangolin and/or unidentified hosts.

scholarly journals First Report of Tomato spotted wilt virus in Blackberry Lily in North America

Plant Disease ◽  
2003 ◽  
Vol 87 (1) ◽  
pp. 102-102 ◽  
Author(s):  
S. Adkins ◽  
L. Breman ◽  
C. A. Baker ◽  
S. Wilson
Keyword(s):  
North America ◽  
Tomato Spotted Wilt Virus ◽  
Amino Acid Sequences ◽  
South Florida ◽  
N Gene ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rt Pcr ◽  
First Report ◽  
Tomato Spotted Wilt ◽  
Wilt Virus

Blackberry lily (Belamcanda chinensis (L.) DC.) is an herbaceous perennial in the Iridaceae characterized by purple-spotted orange flowers followed by persistent clusters of black fruit. In July 2002, virus-like symptoms including chlorotic ringspots and ring patterns were observed on blackberry lily leaves on 2 of 10 plants in a south Florida ornamental demonstration garden. Inclusion body morphology suggested the presence of a Tospovirus. Tomato spotted wilt virus (TSWV) was specifically identified by serological testing using enzyme-linked immunosorbent assay (Agdia, Elkhart, IN). Sequence analysis of a nucleocapsid (N) protein gene fragment amplified by reverse transcription-polymerase chain reaction (RT-PCR) with primers TSWV723 and TSWV722 (1) from total RNA confirmed the diagnosis. Nucleotide and deduced amino acid sequences of a 579 base pair region of the RT-PCR product were 95 to 99% and 95 to 100% identical, respectively, to TSWV N-gene sequences in GenBank. Since these 2-year-old plants were grown on-site from seed, they were likely inoculated by thrips from a nearby source. Together with a previous observation of TSWV in north Florida nursery stock (L. Breman, unpublished), this represents, to our knowledge, the first report of TSWV infection of blackberry lily in North America although TSWV was observed in plants of this species in Japan 25 years ago (2). References: (1) S. Adkins, and E. N. Rosskopf. Plant Dis. 86:1310, 2002. (2) T. Yamamoto and K.-I. Ohata. Bull. Shikoku Agric. Exp. Stn. 30:39, 1977.

scholarly journals Mutations within the Open Reading Frame (ORF) including Ochre stop codon of the Surface Glycoprotein gene of SARS-CoV-2 virus erase potential seed location motifs of human non-coding microRNAs.

2021 ◽  
Author(s):  
Krishna Himmatbhai Goyani ◽  
Shalin Vaniawala ◽  
Pratap Narayan Mukhopadhyaya
Keyword(s):  
Gene Sequence ◽  
Stop Codon ◽  
Early Stage ◽  
Amino Acid Position ◽  
Surface Glycoprotein ◽  
Nucleotide Polymorphisms ◽  
Cellular Mirnas ◽  
Synonymous Mutations ◽  
S Gene ◽  
Epidemic Period

MicroRNA are short and non-coding RNA, 18-25 nucleotides in length. They are produced at the early stage of viral infection. The roles played by cellular miRNAs and miRNA-mediated gene-silencing in the COVID-19 epidemic period is critical in order to develop novel therapeutics. We analysed SARS-CoV-2 Surface Glycoprotein (S) nucleotide sequence originating from India as well as Iran, Australia, Germany, Italy, Russia, China, Japan and Turkey and identified mutation in potential seed location of several human miRNA. Seventy single nucleotide polymorphisms (SNP) were detected in the S gene out of which, 36, 32 and 2 were cases of transitions, transversions and deletions respectively. Eleven human miRNA targets were identified on the reference S gene sequence with a score >80 in the miRDB database. Mutation A845S erased a common binding site of 7 human miRNA (miR-195-5p, miR-16-5p, miR-15b-5p, miR-15a-5p, miR-497-5p, miR-424-5p and miR-6838-5p). A synonymous mutation altered the wild type Ochre stop codon within the S gene sequence (Italy) to Opal thereby changing the seed sequence of miR-511-3p. Similar (synonymous) mutations were detected at amino acid position 659 and 1116 of the S gene where amino acids serine and threonine were retained, abolishing potential seed location for miR-219a-1-3p and miR-20b-3p respectively. The significance of this finding in reference to the strategy to use synthetic miRNA combinations as a novel therapeutic tool is discussed.

scholarly journals Persistence of ambigrammatic narnaviruses requires translation of the reverse open reading frame

2021 ◽  
Author(s):  
Hanna Retallack ◽  
Katerina D. Popova ◽  
Matthew T. Laurie ◽  
Sara Sunshine ◽  
Joseph L. DeRisi
Keyword(s):  
Viral Genome ◽  
Rna Viruses ◽  
Single Gene ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Reading Frame ◽  
Infected Cells ◽  
The Cost ◽  
Overlapping Open Reading Frames ◽  
First Time

Narnaviruses are RNA viruses detected in diverse fungi, plants, protists, arthropods and nematodes. Though initially described as simple single-gene non-segmented viruses encoding RNA-dependent RNA polymerase (RdRp), a subset of narnaviruses referred to as “ambigrammatic” harbor a unique genomic configuration consisting of overlapping open reading frames (ORFs) encoded on opposite strands. Phylogenetic analysis supports selection to maintain this unusual genome organization, but functional investigations are lacking. Here, we establish the mosquito-infecting Culex narnavirus 1 (CxNV1) as a model to investigate the functional role of overlapping ORFs in narnavirus replication. In CxNV1, a reverse ORF without homology to known proteins covers nearly the entire 3.2 kb segment encoding the RdRp. Additionally, two opposing and nearly completely overlapping novel ORFs are found on the second putative CxNV1 segment, the 0.8 kb “Robin” RNA. We developed a system to launch CxNV1 in a naïve mosquito cell line, then showed that functional RdRp is required for persistence of both segments, and an intact reverse ORF is required on the RdRp segment for persistence. Mass spectrometry of persistently CxNV1-infected cells provided evidence for translation of this reverse ORF. Finally, ribosome profiling yielded a striking pattern of footprints for all four CxNV1 RNA strands that was distinct from actively-translating ribosomes on host mRNA or co-infecting RNA viruses. Taken together, these data raise the possibility that the process of translation itself is important for persistence of ambigrammatic narnaviruses, potentially by protecting viral RNA with ribosomes, thus suggesting a heretofore undescribed viral tactic for replication and transmission. IMPORTANCE Fundamental to our understanding of RNA viruses is a description of which strand(s) of RNA are transmitted as the viral genome, relative to which encode the viral proteins. Ambigrammatic narnaviruses break the mold. These viruses, found broadly in fungi, plants, and insects, have the unique feature of two overlapping genes encoded on opposite strands, comprising nearly the full length of the viral genome. Such extensive overlap is not seen in other RNA viruses, and comes at the cost of reduced evolutionary flexibility in the sequence. The present study is motivated by investigating the benefits which balance that cost. We show for the first time a functional requirement for the ambigrammatic genome configuration in Culex narnavirus 1, which suggests a model for how translation of both strands might benefit this virus. Our work highlights a new blueprint for viral persistence, distinct from strategies defined by canonical definitions of the coding strand.

scholarly journals Sequence diversity and evolution of an iflavirus family associated with ticks

2020 ◽  
Author(s):  
Romain Daveu ◽  
Caroline Hervet ◽  
Louane Sigrist ◽  
Davide Sassera ◽  
Aaron Jex ◽  
...  
Keyword(s):  
Cell Line ◽  
Complete Genome ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Rna Viruses ◽  
Ixodes Scapularis ◽  
Fine Scale ◽  
Rna Seq ◽  
Strong Positive Selection ◽  
Synonymous Mutations

AbstractWe studied a family of iflaviruses, a group of RNA viruses frequently found in arthropods, focusing on viruses associated with ticks. Our aim was to bring insight on the evolutionary dynamics of this group of viruses, which may interact with the biology of ticks. We explored systematically de novo RNA-Seq assemblies available for species of ticks which allowed to identify nine new genomes of iflaviruses. The phylogeny of virus sequences was not congruent with that of the tick hosts, suggesting recurrent host changes across tick genera along evolution. We identified five different variants with a complete or near-complete genome in Ixodes ricinus. These sequences were closely related, which allowed a fine-scale estimation of patterns of substitutions: we detected a strong excess of synonymous mutations suggesting evolution under strong positive selection. ISIV, a sequence found in the ISE6 cell line of Ixodes scapularis, was unexpectedly nearidentical with I. ricinus variants, suggesting a contamination of this cell line by I. ricinus material. Overall, our work constitutes a step in the understanding of the interactions between this family of viruses and ticks.

scholarly journals An Unconventional Flavivirus and Other RNA Viruses in the Sea Cucumber (Holothuroidea; Echinodermata) Virome

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1057 ◽  
Author(s):  
Ian Hewson ◽  
Mitchell R. Johnson ◽  
Ian R. Tibbetts
Keyword(s):  
Viral Genome ◽  
Sea Cucumber ◽  
Rna Viruses ◽  
Viral Metagenomics ◽  
Single Specimen ◽  
Wasting Disease ◽  
Double Stranded Rna ◽  
Marine Habitats ◽  
Positive Sense ◽  
Normal Specimen

Sea cucumbers (Holothuroidea; Echinodermata) are ecologically significant constituents of benthic marine habitats. We surveilled RNA viruses inhabiting eight species (representing four families) of holothurian collected from four geographically distinct locations by viral metagenomics, including a single specimen of Apostichopus californicus affected by a hitherto undocumented wasting disease. The RNA virome comprised genome fragments of both single-stranded positive sense and double stranded RNA viruses, including those assigned to the Picornavirales, Ghabrivirales, and Amarillovirales. We discovered an unconventional flavivirus genome fragment which was most similar to a shark virus. Ghabivirales-like genome fragments were most similar to fungal totiviruses in both genome architecture and homology and had likely infected mycobiome constituents. Picornavirales, which are commonly retrieved in host-associated viral metagenomes, were similar to invertebrate transcriptome-derived picorna-like viruses. The greatest number of viral genome fragments was recovered from the wasting A. californicus library compared to the asymptomatic A. californicus library. However, reads from the asymptomatic library recruited to nearly all recovered wasting genome fragments, suggesting that they were present but not well represented in the grossly normal specimen. These results expand the known host range of flaviviruses and suggest that fungi and their viruses may play a role in holothurian ecology.

scholarly journals Analysis of human coronavirus 229E spike and nucleoprotein genes demonstrates genetic drift between chronologically distinct strains

2006 ◽  
Vol 87 (5) ◽  
pp. 1203-1208 ◽  
Author(s):  
Doris Chibo ◽  
Chris Birch
Keyword(s):  
Phylogenetic Analysis ◽  
Respiratory Infections ◽  
N Gene ◽  
Human Coronavirus ◽  
S Gene ◽  
Limited Variation ◽  
Contrast Analysis ◽  
Human Coronaviruses ◽  
Human Coronavirus 229E ◽  
S Genes

Historically, coronaviruses have been recognized as a cause of minor respiratory infections in humans. However, the recent identification of three novel human coronaviruses, one causing severe acute respiratory syndrome (SARS), has prompted further examination of these viruses. Previous studies of geographically and chronologically distinct Human coronavirus 229E (HCoV-229E) isolates have found only limited variation within S gene nucleotide sequences. In contrast, analysis of the S genes of contemporary Human coronavirus OC43 variants identified in Belgium revealed two distinct viruses circulating during 2003 and 2004. Here, the S and N gene sequences of 25 HCoV-229E variants identified in Victoria, Australia, between 1979 and 2004 in patients with symptomatic infections were determined. Phylogenetic analysis showed clustering of the isolates into four groups, with evidence of increasing divergence with time. Evidence of positive selection in the S gene was also established.

scholarly journals Dual Role of a Viral Polymerase in Viral Genome Replication and Particle Self-Assembly

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Xiaoyu Sun ◽  
Serban L. Ilca ◽  
Juha T. Huiskonen ◽  
Minna M. Poranen
Keyword(s):  
Self Assembly ◽  
Viral Genome ◽  
Rna Viruses ◽  
The Self ◽  
Genome Replication ◽  
Double Stranded Rna ◽  
Polymerase Complex ◽  
Viral Genome Replication ◽  
Dsrna Viruses

ABSTRACTDouble-stranded RNA (dsRNA) viruses package several RNA-dependent RNA polymerases (RdRp) together with their dsRNA genome into an icosahedral protein capsid known as the polymerase complex. This structure is highly conserved among dsRNA viruses but is not found in any other virus group. RdRp subunits typically interact directly with the main capsid proteins, close to the 5-fold symmetric axes, and perform viral genome replication and transcription within the icosahedral protein shell. In this study, we utilizedPseudomonasphage Φ6, a well-established virus self-assembly model, to probe the potential roles of the RdRp in dsRNA virus assembly. We demonstrated that Φ6 RdRp accelerates the polymerase complex self-assembly process and contributes to its conformational stability and integrity. We highlight the role of specific amino acid residues on the surface of the RdRp in its incorporation during the self-assembly reaction. Substitutions of these residues reduce RdRp incorporation into the polymerase complex during the self-assembly reaction. Furthermore, we determined that the overall transcription efficiency of the Φ6 polymerase complex increased when the number of RdRp subunits exceeded the number of genome segments. These results suggest a mechanism for RdRp recruitment in the polymerase complex and highlight its novel role in virion assembly, in addition to the canonical RNA transcription and replication functions.IMPORTANCEDouble-stranded RNA viruses infect a wide spectrum of hosts, including animals, plants, fungi, and bacteria. Yet genome replication mechanisms of these viruses are conserved. During the infection cycle, a proteinaceous capsid, the polymerase complex, is formed. An essential component of this capsid is the viral RNA polymerase that replicates and transcribes the enclosed viral genome. The polymerase complex structure is well characterized for many double-stranded RNA viruses. However, much less is known about the hierarchical molecular interactions that take place in building up such complexes. Using the bacteriophage Φ6 self-assembly system, we obtained novel insights into the processes that mediate polymerase subunit incorporation into the polymerase complex for generation of functional structures. The results presented pave the way for the exploitation and engineering of viral self-assembly processes for biomedical and synthetic biology applications. An understanding of viral assembly processes at the molecular level may also facilitate the development of antivirals that target viral capsid assembly.

scholarly journals Targeting viral genome synthesis as broad-spectrum approach against RNA virus infections

2020 ◽  
Vol 28 ◽  
pp. 204020662097678
Author(s):  
Johanna Huchting
Keyword(s):  
Broad Spectrum ◽  
Viral Genome ◽  
De Novo ◽  
Rna Viruses ◽  
Rna Virus ◽  
Antiviral Drug ◽  
Building Blocks ◽  
Structural Features ◽  
Pathogen Transmission ◽  
Nucleotide Synthesis

Zoonotic spillover, i.e. pathogen transmission from animal to human, has repeatedly introduced RNA viruses into the human population. In some cases, where these viruses were then efficiently transmitted between humans, they caused large disease outbreaks such as the 1918 flu pandemic or, more recently, outbreaks of Ebola and Coronavirus disease. These examples demonstrate that RNA viruses pose an immense burden on individual and public health with outbreaks threatening the economy and social cohesion within and across borders. And while emerging RNA viruses are introduced more frequently as human activities increasingly disrupt wild-life eco-systems, therapeutic or preventative medicines satisfying the “one drug-multiple bugs”-aim are unavailable. As one central aspect of preparedness efforts, this review digs into the development of broadly acting antivirals via targeting viral genome synthesis with host- or virus-directed drugs centering around nucleotides, the genomes’ universal building blocks. Following the first strategy, selected examples of host de novo nucleotide synthesis inhibitors are presented that ultimately interfere with viral nucleic acid synthesis, with ribavirin being the most prominent and widely used example. For directly targeting the viral polymerase, nucleoside and nucleotide analogues (NNAs) have long been at the core of antiviral drug development and this review illustrates different molecular strategies by which NNAs inhibit viral infection. Highlighting well-known as well as recent, clinically promising compounds, structural features and mechanistic details that may confer broad-spectrum activity are discussed. The final part addresses limitations of NNAs for clinical development such as low efficacy or mitochondrial toxicity and illustrates strategies to overcome these.

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