Evolutionary dynamics of the SARS-CoV-2 ORF8 accessory gene.
TL;DR: It is shown that ORF8 is poorly conserved among related coronaviruses, and its structural plasticity and high diversity suggest an important role in SARS-CoV-2 pathogenicity.
About: This article is published in Infection, Genetics and Evolution.The article was published on 2020-11-01 and is currently open access. It has received 92 citations till now. The article focuses on the topics: Population & Gene.
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TL;DR: The major variant of concerns (VOCs) have shared mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins, mostly on the S1 unit and resulted in higher transmissibility rate and affect viral virulence and clinical outcome as discussed by the authors.
Abstract: The major variant of concerns (VOCs) have shared mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins, mostly on the S1 unit and resulted in higher transmissibility rate and affect viral virulence and clinical outcome. The spike protein mutations and other non-structural protein mutations in the VOCs may lead to escape approved vaccinations in certain extend. We will discuss these VOC mutations and discuss the need for combination therapeutic strategies targeting viral cycle and immune host responses.
156 citations
TL;DR: A review on the current knowledge of SARS-CoV-2 accessory proteins is summarized updating new research that could be critical in understanding SARSCoV2 interaction with the host.
Abstract: There are still many unanswered questions concerning viral SARS-CoV-2 pathogenesis in COVID-19. Accessory proteins in SARS-CoV-2 consist of eleven viral proteins whose roles during infection are still not completely understood. Here, a review on the current knowledge of SARS-CoV-2 accessory proteins is summarized updating new research that could be critical in understanding SARS-CoV-2 interaction with the host. Some accessory proteins such as ORF3b, ORF6, ORF7a and ORF8 have been shown to be important IFN-I antagonists inducing an impairment in the host immune response. In addition, ORF3a is involved in apoptosis whereas others like ORF9b and ORF9c interact with cellular organelles leading to suppression of the antiviral response in infected cells. However, possible roles of ORF7b and ORF10 are still awaiting to be described. Also, ORF3d has been reassigned. Relevant information on the knowns and the unknowns in these proteins is analyzed, which could be crucial for further understanding of SARS-CoV-2 pathogenesis and to design strategies counteracting their actions evading immune responses in COVID-19.
134 citations
TL;DR: In this paper, the authors investigated the population structure and genomic complexity of SARS-CoV-2 in Rio Grande do Sul, the southernmost state in Brazil, and identified two independent events of co-infection caused by the occurrence of B.1.28 (E484K) and other variants in Brazil.
97 citations
TL;DR: In this article, a preliminary opinion about the disease, origin and life cycle of SARS-CoV-2, roles of virus proteins in pathogenesis, commonalities, and differences between different corona viruses are discussed.
Abstract: The outbreak of a novel coronavirus associated with acute respiratory disease, called COVID-19, marked the introduction of the third spillover of an animal coronavirus (CoV) to humans in the last two decades. The genome analysis with various bioinformatics tools revealed that the causative pathogen (SARS-CoV-2) belongs to the subgenus Sarbecovirus of the genus Betacoronavirus, with highly similar genome as bat coronavirus and receptor-binding domain (RBD) of spike glycoprotein as Malayan pangolin coronavirus. Based on its genetic proximity, SARS-CoV-2 is likely to have originated from bat-derived CoV and transmitted to humans via an unknown intermediate mammalian host, probably Malayan pangolin. Further, spike protein S1/S2 cleavage site of SARS-CoV-2 has acquired polybasic furin cleavage site which is absent in bat and pangolin suggesting natural selection either in an animal host before zoonotic transfer or in humans following zoonotic transfer. In the current review, we recapitulate a preliminary opinion about the disease, origin and life cycle of SARS-CoV-2, roles of virus proteins in pathogenesis, commonalities, and differences between different corona viruses. Moreover, the crystal structures of SARS-CoV-2 proteins with unique characteristics differentiating it from other CoVs are discussed. Our review also provides comprehensive information on the molecular aspects of SARS-CoV-2 including secondary structures in the genome and protein-protein interactions which can be useful to understand the aggressive spread of the SARS-CoV-2. The mutations and the haplotypes reported in the SARS-CoV-2 genome are summarized to understand the virus evolution.
88 citations
TL;DR: This minireview summarizes the current knowledge on the SARS-CoV-2 ORF8 protein in perspective to its potential as antiviral target and with special emphasis on the biochemical, biophysical and structural aspects of its molecular biology.
85 citations
Cites background from "Evolutionary dynamics of the SARS-C..."
...Ser67-Lys68 tract [16], are all exposed to the solvent and therefore unlikely to cause major structural perturbations when...
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...substitution of three internal residues (Gly66-Ser67-Lys68) with a Glutamic acid [16]....
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References
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TL;DR: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score.
88,255 citations
Additional excerpts
...2) as a query in blastn (discontiguous megablast), blastx and blastp searched against the Nucleotide collection (nt) database (Altschul et al., 1990)....
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TL;DR: MrBayes 3 performs Bayesian phylogenetic analysis combining information from different data partitions or subsets evolving under different stochastic evolutionary models to analyze heterogeneous data sets and explore a wide variety of structured models mixing partition-unique and shared parameters.
Abstract: Summary: MrBayes 3 performs Bayesian phylogenetic analysis combining information from different data partitions or subsets evolving under different stochastic evolutionary models. This allows the user to analyze heterogeneous data sets consisting of different data types—e.g. morphological, nucleotide, and protein— and to explore a wide variety of structured models mixing partition-unique and shared parameters. The program employs MPI to parallelize Metropolis coupling on Macintosh or UNIX clusters.
25,931 citations
"Evolutionary dynamics of the SARS-C..." refers methods in this paper
...7a) software (Ronquist and Huelsenbeck, 2003) running on the CIPRES Science Gateway (Miller et al....
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TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Abstract: Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV. Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.
16,857 citations
"Evolutionary dynamics of the SARS-C..." refers background in this paper
...large global outbreak with severe public health consequences (Wu et al., 2020; Zhou et al., 2020)....
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...5 placed SARS-CoV-2 ORF8 close to the RaTG13 previously detected in bats from the Yunnan province (Zhou et al., 2020), with a 97% sequence identity (Fig....
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...The novel SARS-CoV-2 shares nearly 96% similarity to the bat coronavirus isolate RaTG13, suggesting these animals are the likely natural reservoir of the virus (Boni et al., 2020; Lu et al., 2020; Zhou et al., 2020)....
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TL;DR: The objective of this web server is to provide easy access to RNA and DNA folding and hybridization software to the scientific community at large by making use of universally available web GUIs (Graphical User Interfaces).
Abstract: The abbreviated name,‘mfold web server’,describes a number of closely related software applications available on the World Wide Web (WWW) for the prediction of the secondary structure of single stranded nucleic acids. The objective of this web server is to provide easy access to RNA and DNA folding and hybridization software to the scientific community at large. By making use of universally available web GUIs (Graphical User Interfaces),the server circumvents the problem of portability of this software. Detailed output,in the form of structure plots with or without reliability information,single strand frequency plots and ‘energy dot plots’, are available for the folding of single sequences. A variety of ‘bulk’ servers give less information,but in a shorter time and for up to hundreds of sequences at once. The portal for the mfold web server is http://www.bioinfo.rpi.edu/applications/ mfold. This URL will be referred to as ‘MFOLDROOT’.
12,535 citations
"Evolutionary dynamics of the SARS-C..." refers methods in this paper
...RNA secondary structures were predicted using the RNA Folding Form of the Mfold web server (Zuker, 2003) at a temperature of 37 °C....
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TL;DR: A method for constructing networks from recombination-free population data that combines features of Kruskal's algorithm for finding minimum spanning trees by favoring short connections, and Farris's maximum-parsimony (MP) heuristic algorithm, which sequentially adds new vertices called "median vectors", except that the MJ method does not resolve ties.
Abstract: Reconstructing phylogenies from intraspecific data (such as human mitochondrial DNA variation) is often a challenging task because of large sample sizes and small genetic distances between individuals. The resulting multitude of plausible trees is best expressed by a network which displays alternative potential evolutionary paths in the form of cycles. We present a method ("median joining" [MJ]) for constructing networks from recombination-free population data that combines features of Kruskal's algorithm for finding minimum spanning trees by favoring short connections, and Farris's maximum-parsimony (MP) heuristic algorithm, which sequentially adds new vertices called "median vectors", except that our MJ method does not resolve ties. The MJ method is hence closely related to the earlier approach of Foulds, Hendy, and Penny for estimating MP trees but can be adjusted to the level of homoplasy by setting a parameter epsilon. Unlike our earlier reduced median (RM) network method, MJ is applicable to multistate characters (e.g., amino acid sequences). An additional feature is the speed of the implemented algorithm: a sample of 800 worldwide mtDNA hypervariable segment I sequences requires less than 3 h on a Pentium 120 PC. The MJ method is demonstrated on a Tibetan mitochondrial DNA RFLP data set.
9,937 citations
"Evolutionary dynamics of the SARS-C..." refers methods in this paper
...Median-joining network (Bandelt et al., 1999) and mismatch distribution were calculated using the Network V10....
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