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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (8)

ORF1ab (8)

ProteinN (4)

ORF3a (4)

ORF8 (2)


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SARS-CoV-2 Proteins
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    SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study

    Authors: Andrew G Letizia; Yongchao Ge; Sindhu Vangeti; Carl Goforth; Dawn L Weir; Natalia A Kuzmina; Hua Wei Chen; Dan Ewing; Alessandra Soares-Schanoski; Mary-Catherine George; William D Graham; Franca Jones; Preeti Bharaj; Rhonda A Lizewski; Stephen A Lizewski; Jan Marayag; Nada Marjanovic,; Clare Miller; Sagie Mofsowitz; Venugopalan D Nair; Edgar Nunez; Danielle M Parent; Chad K Porter; Ernesto Santa Ana; Megan Schilling; Daniel Stadlbauer; Victor Sugiharto; Michael S Termini; Peifang Sun; Russell P Tracy; Florian Krammer; Alexander Bukreyev; Ramos Irene; Stuart C Sealfon

    doi:10.1101/2021.01.26.21250535 Date: 2021-01-29 Source: medRxiv

    Background: The risk of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) subsequent infection among seropositive young adults was studied prospectively. Methods: The study population comprised 3,249 predominantly male, 18-20-year-old Marine recruits. Upon arrival at a Marine-supervised two-week quarantine, participants were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a 1:150 dilution or greater on receptor binding domain and full-length spike protein PROTEIN enzyme-linked immunosorbent (ELISA) assays. SARS-CoV-2 infection MESHD was assessed by PCR at initiation, middle and end of the quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, we performed three biweekly PCR tests in both seropositive and in seronegative groups once recruits left quarantine and entered basic training and baseline neutralizing antibody titers on all subsequently infected seropositive MESHD and selected seropositive uninfected participants. Findings: Among 189 seropositive participants, 19 (10.1%) had at least one positive PCR test for SARS-CoV-2 during the six-week follow-up (1.1 cases per person-year). In contrast, 1,079 (48.0%) of the 2,247 seronegative participants tested positive (6.2 cases per person-year). The incidence rate ratio was 0.18 (95% CI 0.11-0.28, p<0.00001). Among seropositive recruits, infection was associated with lower baseline full-length spike protein PROTEIN IgG titers (p<0.0001). Compared with seronegative recruits, seropositive recruits had about 10-fold lower viral loads ( ORF1ab PROTEIN gene, p<0.005), and trended towards shorter duration of PCR positivity (p=0.18) and more frequent asymptomatic infections (p=0.13). Among seropositive participants, baseline neutralizing titers were detected in 45 of 54 (83.3%) uninfected and in 6 of 19 (31.6%) infected participants during the 6 weeks of observation (ID50 difference p

    Structure-function investigation of a new VUI-202012/01 SARS-CoV-2 variant

    Authors: Jasdeep Singh; Nasreen Z Ehtesham; Syed Asad Rahman; Yakob G. Tsegay; Daniel S. Abebe; Mesay G. Edo; Endalkachew H. Maru; Wuletaw C. Zewde; Lydia K. Naylor; Dejen F. Semane; Menayit T. Deresse; Bereket B. Tezera; Lovisa Skoglund; Jamil Yousef; Elisa Pin; Wanda Christ; Mikaela Olausson; My Hedhammar; Hanna Tegel; Sara Mangsbo; Mia Phillipson; Anna Manberg; Sophia Hober; Peter Nilsson; Charlotte Thalin; Samuel Bates; Chevaun Morrison-Smith; Benjamin Nicholson; Edmond Wong; Leena El-Mufti; Michael Kann; Anna Bolling; Brooke Fortin; Hayden Ventresca; Wen Zhou; Santiago Pardo; Megan Kwock; Aditi Hazra; Leo Cheng; Rushdy Ahmad; James A. Toombs; Rebecca Larson; Haley Pleskow; Nell Meosky Luo; Christina Samaha; Unnati M. Pandya; Pushpamali De Silva; Sally Zhou; Zakary Ganhadeiro; Sara Yohannes; Rakiesha Gay; Jacqueline Slavik; Shibani S. Mukerji; Petr Jarolim; David R. Walt; Becky C. Carlyle; Lauren L. Ritterhouse; Sara Suliman

    doi:10.1101/2021.01.01.425028 Date: 2021-01-04 Source: bioRxiv

    The SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus MESHD) has accumulated multiple mutations during its global circulation. Recently, a new strain of SARS-CoV-2 (VUI 202012/01) had been identified leading to sudden spike in COVID-19 MESHD cases in South-East England. The strain has accumulated 23 mutations which have been linked to its immune evasion and higher transmission capabilities. Here, we have highlighted structural-function impact of crucial mutations occurring in spike (S), ORF8 PROTEIN and nucleocapsid (N) protein PROTEIN of SARS-CoV-2. Some of these mutations might confer higher fitness to SARS-CoV-2 MESHD. SummarySince initial outbreak of COVID-19 MESHD in Wuhan city of central China, its causative agent; SARS-CoV-2 virus has claimed more than 1.7 million lives out of 77 million populations and still counting. As a result of global research efforts involving public-private-partnerships, more than 0.2 million complete genome sequences have been made available through Global Initiative on Sharing All Influenza Data (GISAID). Similar to previously characterized coronaviruses (CoVs), the positive-sense single-stranded RNA SARS-CoV-2 genome codes for ORF1ab PROTEIN non-structural proteins (nsp(s)) followed by ten or more structural/nsps [1, 2]. The structural proteins include crucial spike (S), nucleocapsid (N PROTEIN), membrane (M), and envelope (E) proteins PROTEIN. The S protein PROTEIN mediates initial contacts with human hosts while the E and M proteins PROTEIN function in viral assembly and budding. In recent reports on evolution of SARS-CoV-2, three lineage defining non-synonymous mutations; namely D614G in S protein PROTEIN (Clade G), G251V in ORF3a PROTEIN (Clade V) and L84S in ORF 8 (Clade S) were observed [2-4]. The latest pioneering works by Plante et al and Hou et al have shown that compared to ancestral strain, the ubiquitous D614G variant (clade G) of SARS-CoV-2 exhibits efficient replication in upper respiratory tract epithelial cells and transmission, thereby conferring higher fitness MESHD [5, 6]. As per latest WHO reports on COVID-19 MESHD, a new strain referred as SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01) had been identified as a part of virological and epidemiological analysis, due to sudden rise MESHD in COVID-19 MESHD detected cases in South-East England [7]. Preliminary reports from UK suggested higher transmissibility (increase by 40-70%) of this strain, escalating Ro (basic reproduction number) of virus to 1.5-1.7 [7, 8]. This apparent fast spreading variant inculcates 23 mutations; 13 non-synonymous, 6 synonymous and 4 amino acid deletions [7]. In the current scenario, where immunization programs have already commenced in nations highly affected by COVID-19 MESHD, advent of this new strain variant has raised concerns worldwide on its possible role in disease severity and antibody responses. The mutations also could also have significant impact on diagnostic assays owing to S gene target failures.

    Horizontal gene transfer and recombination analysis of SARS-CoV-2 genes helps discover its close relatives and shed light on its origin

    Authors: Vladimir Makarenkov; Bogdan Mazoure; Guillaume Rabusseau; Pierre Legendre; Gustavo Ferrer; Xiaoping Jiang; Ya-Nan Dai; Haiyan Zhao; Lucas Adams; Michael Holtzman; Adam Bailey; James Brett Case; Daved Fremont; Robyn S Klein; Michael Diamond; Adrianus Boon

    doi:10.1101/2020.12.03.410233 Date: 2020-12-03 Source: bioRxiv

    The SARS-CoV-2 pandemic is among the most dangerous infectious diseases that have emerged in recent history. Human CoV strains discovered during previous SARS outbreaks have been hypothesized to pass from bats to humans using intermediate hosts, e.g. civets for SARS-CoV MESHD and camels for MERS-CoV. The discovery of an intermediate host of SARS-CoV-2 and the identification of specific mechanism of its emergence in humans are topics of primary evolutionary importance. In this study we investigate the evolutionary patterns of 11 main genes of SARS-CoV-2. Previous studies suggested that the genome of SARS-CoV-2 is highly similar to the horseshoe bat coronavirus RaTG13 for most of the genes and to some Malayan pangolin coronavirus MESHD (CoV) strains for the receptor binding (RB) domain of the spike protein PROTEIN. We provide a detailed list of statistically significant horizontal gene transfer and recombination events (both intergenic and intragenic) inferred for each of 11 main genes of the SARS-Cov-2 genome. Our analysis reveals that two continuous regions of genes S and N of SARS-CoV-2 may result from intragenic recombination between RaTG13 and Guangdong (GD) Pangolin CoVs. Statistically significant gene transfer-recombination events between RaTG13 and GD Pangolin CoV MESHD have been identified in region [1215-1425] of gene S and region [534-727] of gene N PROTEIN. Moreover, some significant recombination events between the ancestors of SARS-CoV-2, RaTG13, GD Pangolin CoV MESHD and bat CoV ZC45-ZXC21 coronaviruses have been identified in genes ORF1ab PROTEIN, S, ORF3a PROTEIN, ORF7a PROTEIN, ORF8 PROTEIN and N. Furthermore, topology-based clustering of gene trees inferred for 25 CoV organisms revealed a three-way evolution of coronavirus genes, with gene phylogenies of ORF1ab PROTEIN, S and N forming the first cluster, gene phylogenies of ORF3a PROTEIN, E, M, ORF6 PROTEIN, ORF7a PROTEIN, ORF7b PROTEIN and ORF8 PROTEIN forming the second cluster, and phylogeny of gene ORF10 PROTEIN forming the third cluster. The results of our horizontal gene transfer and recombination analysis suggest that SARS-Cov-2 could not only be a chimera resulting from recombination of the bat RaTG13 and Guangdong pangolin coronaviruses but also a close relative of the bat CoV ZC45 and ZXC21 strains. They also indicate that a GD pangolin may be an intermediate host of SARS-CoV-2.

    Proteo-genomic analysis of SARS-CoV-2: A clinical landscape of SNPs, COVID-19 MESHD proteome and host responses

    Authors: Sheetal Tushir; Sathisha Kamanna; Sujith S Nath; Aishwarya Bhat; Steffimol Rose; Advait R Aithal; Utpal Tatu

    doi:10.1101/2020.11.27.20237032 Date: 2020-11-30 Source: medRxiv

    A novel severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the causative agent of COVID-19 MESHD and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic analysis using next generation sequencing (NGS) and mass-spectrometry on nasopharyngeal swabs of COVID-19 MESHD patients to examine clinical genome and proteome. Our study confirms the hyper mutability of SARS-CoV-2 showing multiple SNPs. NGS analysis detected 27 mutations of which 14 are synonymous, 11 are missense and 2 are extragenic in nature. Phylogenetic analysis of SARS-CoV-2 isolates indicated their close relation to Bangladesh isolate and multiple origins of isolates within a country. Our proteomic analysis, for the first time identified 13 different SARS-CoV-2 proteins from the clinical swabs. Of the total 41 peptides captured by HRMS, 8 matched to nucleocapsid protein PROTEIN, 2 to ORF9b PROTEIN, 1 to spike glycoprotein PROTEIN and ORF3a PROTEIN, with remaining mapping to ORF1ab PROTEIN polyprotein. Additionally, host proteome analysis revealed several key host proteins to be uniquely expressed in COVID-19 MESHD patients. Pathway analysis of these proteins points towards modulation in immune response, especially involving neutrophil and IL-12 mediated signaling. Besides revealing the aspects of host-virus pathogenesis, our study opens new avenues to develop better diagnostic markers and therapeutics.

    Understanding Structural Malleability of the SARS-CoV-2 Proteins and their Relation to the Comorbidities

    Authors: Sagnik Sen; Ashmita Dey; Sanghamitra Bandyopadhyay; Ujjwal Maulik; Vladimir Uversky

    doi:10.21203/rs.3.rs-82352/v1 Date: 2020-09-23 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease MESHD ( CoVID-19 MESHD), is a part of the β-coronaviridae family. In comparison with two other members of this family of coronaviruses infecting humans ( SARS-CoV and Middle East Respiratory Syndrome MESHD ( MERS MESHD) CoV), SARS-CoV-2 showed the most severe effects on the entire Earth population causing world-wide CoVID-19 pandemic MESHD. SARS-CoV-2 contains five major protein classes, such as four structural proteins (Nucleocapsid (N PROTEIN), Membrane (M), Envelop (E), and Spike Glycoprotein PROTEIN (S)) and Replicase polyproteins (R), which are synthesized as two polyproteins ( ORF1a PROTEIN and ORF1ab PROTEIN) that are subsequently processed into 12 nonstructural proteins by three viral proteases. All these proteins share high sequence similarity with their SARS-CoV counterparts. Due to the severity of the current situation, most of the SARS-CoV-2-related research is focused on finding therapeutic solutions and the analysis of comorbidities during infection. However, studies on the peculiarities of the amino acid sequences of viral protein classes and their structure space analysis throughout the evolutionary time-frame are limited. At the same time, due to their structural malleability, viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins, which may lead to comorbidities during the infection and at the post infection stage. To fill these gaps, we conducted the evolutionary sequence-structure analysis of the viral protein classes to evaluate the rate of their evolutionary malleability. We also looked at the intrinsic disorder propensities of these viral proteins and confirmed that although they typically do not have long intrinsically disordered regions (IDRs), all of them have at least some levels of intrinsic disorder MESHD. Furthermore, short IDRs found in viral proteins are extremely effective and prioritize the proteins for host cell interactions, which may lead to host cell dysfunction. Next, the associations of viral proteins with the host cell proteins were studied, and a list of diseases which are associated with such host cell proteins was developed. Other than the usual set of diseases, we have identified some maladies, which may happen after the recovery from the infections. Comparison of the expression rates of the host cell proteins during the diseases suggested the existence of two distinct classes. First class includes proteins, which are directly associated with certain sets of diseases, where they have shared similar activities. Second class is related to the cytokine storm-mediated pro- inflammation MESHD (already known for its role in acute respiratory distress syndrome MESHD, ARDS MESHD), and neuroinflammation may trigger some of the neurological malignancies and neurodegenerative and neuropsychiatric diseases MESHD. Finally, since the transmembrane serine protease 2 ( TMPRSS2 HGNC), which is one of the leading proteins associated with the viral uptake, is an androgen-mediated protein, our study suggested that males and postmenopausal females can be more susceptible to the SARS-CoV-2 infection MESHD.

    Global and Local Mutations in Bangladeshi SARS-CoV-2 Genomes

    Authors: Md Mahbub Hasan; Rasel Das; Md. Rasheduzzaman; Md Hamed Hussain; Nazmul Hasan Muzahid; Asma Salauddin; Meheadi Hasan Rumi; S M Mahbubur Rashid; AMAM Zonaed Siddiki; Adnan Mannan; Andreas Cornelius; Patricia Schildknecht; Mirela Matzner; Martin Haenggi; Marco Franchini; Yvonne Kaufmann; Iris Schlegel; Chloe Iss; Thamar Loser; Susanne Mangold; Christel Herzog; Dieter Schiegg; Christian Reichen; Filip Radom; Andreas Bosshart; Andreas Lehmann; Micha A. Haeuptle; Alexander Zuercher; Toni Vagt; Gabriel Sigrist; Marcel Straumann; Karl Proba; Niina Veitonmaki; Keith M. Dawson; Christof Zitt; Jennifer Mayor; Sarah Ryter; Heyrhyoung Lyoo; Chunyan Wang; Wentao Li; Ieva Drulyte; H. Kaspar Binz; Leon de Waal; Koert J. Stittelaar; Seth Lewis; Daniel Steiner; Frank J.M. van Kuppeveld; Olivier Engler; Berend-Jan Bosch; Michael T. Stumpp; Patrick Amstutz

    doi:10.1101/2020.08.25.267658 Date: 2020-08-26 Source: bioRxiv

    Corona Virus Disease-2019 ( COVID-19 MESHD) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome-CoronaVirus-2 MESHD (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations and pathogenesis. Nearly 0.4 million mutations were identified so far in [~]60,000 SARS-CoV-2 genomic sequences. In this study, we compared 207 of SARS-CoV-2 genomes reported from different parts of Bangladesh and their comparison with 467 globally reported sequences to understand the origin of viruses, possible patterns of mutations, availability of unique mutations, and their apparent impact on pathogenicity of the virus in victims of Bangladeshi population. Phylogenetic analyses indicates that in Bangladesh, SARS-CoV-2 viruses might arrived through infected travelers from European countries, and the GR clade was found as predominant in this region. We found 2602 mutations including 1602 missense mutations, 612 synonymous mutations, 36 insertions and deletions with 352 other mutations types. In line with the global trend, D614G mutation in spike glycoprotein PROTEIN was predominantly high (95.6%) in Bangladeshi isolates. Interestingly, we found the average number of mutations in ORF1ab PROTEIN, S, ORF3a PROTEIN, M and N of genomes, having nucleotide shift at G614 (n=459), were significantly higher (p[≤]0.001) than those having mutation at D614 (n=215). Previously reported frequent mutations such as P4715L, D614G, R203K, G204R and I300F were also prevalent in Bangladeshi isolates. Additionally, 87 unique amino acid changes were revealed and were categorized as originating from different cities of Bangladesh. The analyses would increase our understanding of variations in virus genomes circulating in Bangladesh and elsewhere and help develop novel therapeutic targets against SARS-CoV-2.

    Antigenic evolution on global scale reveals potential natural selection of SARS-CoV-2 by pre-existing cross-reactive T cell immunity

    Authors: Chengdong Zhang; Xuanxuan Jin; Xianyang Chen; Qibin Leng; Tianyi Qiu

    doi:10.1101/2020.06.16.154591 Date: 2020-06-16 Source: bioRxiv

    The mutation pattern of severe acute respiratory syndrome-coronavirus MESHD 2 (SARS-CoV-2) is constantly changing with the places of transmission, but the reason remains to be revealed. Here, we presented the study that comprehensively analyzed the potential selective pressure of immune system restriction, which can drive mutations in circulating SARS-CoV-2 isolates. The results showed that the most common mutation sites of SARS-CoV-2 proteins were located on the non-structural protein ORF1ab PROTEIN and the structural protein Spike PROTEIN. Further analysis revealed mutations in cross-reactive epitopes between SARS-CoV-2 and seasonal coronavirus may help SARS-CoV-2 to escape cellular immunity under the long-term and large-scale community transmission. Meanwhile, the mutations on Spike protein PROTEIN may enhance the ability of SARS-CoV-2 to enter the host cells and escape the recognition of B-cell immunity. This study will increase the understanding of the evolutionary direction and warn about the potential immune escape ability of SARS-CoV-2, which may provide important guidance for the potential vaccine design.

    Characterization of accessory genes in coronavirus genomes

    Authors: Christian Jean Michel; Claudine Mayer; Olivier Poch; Julie Dawn Thompson

    doi:10.21203/rs.3.rs-32190/v1 Date: 2020-05-28 Source: ResearchSquare

    Background: The Covid19 MESHD infection is caused by the SARS-CoV-2 virus, a novel member of the coronavirus (CoV) family. CoV genomes code for a ORF1a PROTEIN / ORF1ab PROTEIN polyprotein and four structural proteins widely studied as major drug targets. The genomes also contain a variable number of open reading frames (ORFs) coding for accessory proteins that are not essential for virus replication, but appear to have a role in pathogenesis. The accessory proteins have been less well characterized and are difficult to predict by classical bioinformatics methods.Methods: We propose a computational tool GOFIX to characterize potential ORFs in virus genomes. In particular, ORF coding potential is estimated by searching for enrichment in motifs of the X circular code, that is known to be over-represented in the reading frames of viral genes.Results: We applied GOFIX to study the SARS-CoV-2 and related genomes including SARS-CoV MESHD and SARS-like viruses from bat, civet and pangolin hosts, focusing on the accessory proteins. Our analysis provides evidence supporting the presence of overlapping ORFs 7b, 9b and 9c in all the genomes and thus helps to resolve some differences in current genome annotations. In contrast, we predict that ORF3b PROTEIN is not functional in all genomes. Novel putative ORFs were also predicted, including a truncated form of the ORF10 PROTEIN previously identified in SARS-CoV-2 and a little known ORF overlapping the Spike protein PROTEIN in Civet-CoV and SARS-CoV MESHD.Conclusions: Our findings contribute to characterizing sequence properties of accessory genes of SARS coronaviruses MESHD, and especially the newly acquired genes making use of overlapping reading frames.

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