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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ORF10 (21)

ProteinS (9)

ORF8 (8)

ORF7a (7)

ORF1ab (7)


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SARS-CoV-2 Proteins
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    Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses

    Authors: Hong Zhou; Jingkai Ji; Xing Chen; Yuhai Bi; Juan Li; Tao Hu; Hao Song; Yanhua Chen; Mingxue Cui; Yanyan Zhang; Alice C. Hughes; Edward C. Holmes; Weifeng Shi

    doi:10.1101/2021.03.08.434390 Date: 2021-03-08 Source: bioRxiv

    Although a variety of SARS-CoV-2 related coronaviruses have been identified, the evolutionary origins of this virus remain elusive. We describe a meta-transcriptomic study of 411 samples collected from 23 bat species in a small (~1100 hectare) region in Yunnan province, China, from May 2019 to November 2020. We identified coronavirus contigs in 40 of 100 sequencing libraries, including seven representing SARS-CoV-2-like contigs. From these data we obtained 24 full-length coronavirus genomes, including four novel SARS-CoV-2 related and three SARS-CoV MESHD related genomes. Of these viruses, RpYN06 exhibited 94.5% sequence identity to SARS-CoV-2 across the whole genome and was the closest relative of SARS-CoV-2 in the ORF1ab PROTEIN, ORF7a PROTEIN, ORF8 PROTEIN, N, and ORF10 PROTEIN genes. The other three SARS-CoV-2 related coronaviruses were nearly identical in sequence and clustered closely with a virus previously identified in pangolins from Guangxi, China, although with a genetically distinct spike gene sequence. We also identified 17 alphacoronavirus genomes, including those closely related to swine acute diarrhea syndrome MESHD virus and porcine epidemic diarrhea virus MESHD. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species in Southeast Asia and southern China, with the largest contiguous hotspots extending from South Lao HGNC and Vietnam to southern China. Our study highlights both the remarkable diversity of bat viruses at the local scale and that relatives of SARS-CoV-2 and SARS-CoV circulate in wildlife species in a broad geographic region of Southeast Asia and southern China. These data will help guide surveillance efforts to determine the origins of SARS-CoV-2 and other pathogenic coronaviruses.

    Designing a new multi epitope-based vaccine against COVID-19 MESHD disease: an immunoinformatic study based on reverse vaccinology approach

    Authors: Afshin Samimi Nemati; Majid Tafrihi; Fatemeh Sheikhi; Abolfazl Rostamian Tabari; Amirhossein Haditabar

    doi:10.21203/rs.3.rs-206270/v1 Date: 2021-02-04 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has currently caused a significant pandemic among worldwide populations. The transmission speed and the high rate of mortality caused by the disease necessitate studies for the rapid designing and effective vaccine production. The purpose of this study is to predict and design a novel multi-epitope vaccine against the SARS-CoV-2 virus using bioinformatics approaches. Coronavirus envelope proteins PROTEIN, ORF7b PROTEIN, ORF8 PROTEIN, ORF10 PROTEIN, and NSP9 PROTEIN were selected as targets for epitope mapping using IEDB and BepiPred 2.0 Servers. Also, molecular docking studies were performed to determine the candidate vaccine's affinity to TLR3 HGNC, TLR4 HGNC, MHC I, and MHC II molecules. Thirteen epitopes were selected to construct the multi-epitope vaccine. We found that the constructed peptide has valuable antigenicity, stability, and appropriate half-life. The Ramachandran plot approved the quality of the predicted model after the refinement process. Molecular docking investigations revealed that antibody-mode in the Cluspro 2.0 server showed the lowest binding energy for MHCI, MHCII, TLR3 HGNC, and TLR4 HGNC. This study confirmed that the designed vaccine has a good antigenicity and stability and could be a proper vaccine candidate against the COVID-19 MESHD infectious disease MESHD though, in vitro and in vivo experiments are necessary to complete and confirm our results.

    Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection

    Authors: Jessie J.-Y. Chang; Daniel Rawlinson; Miranda E. Pitt; George Taiaroa; Josie Gleeson; Chenxi Zhou; Francesca L. Mordant; Ricardo De Paoli-Iseppi; Leon Caly; Damian F. J. Purcell; Tim P. Stinear; Sarah L. Londrigan; Michael B. Clark; Deborah A. Williamson; Kanta Subbarao; Lachlan J M Coin

    doi:10.1101/2020.12.22.423893 Date: 2020-12-22 Source: bioRxiv

    SARS-CoV-2 uses subgenomic (sg)RNA to produce viral proteins for replication and immune evasion. We applied long-read RNA and cDNA sequencing to in vitro human and primate infection models to study transcriptional dynamics. Transcription-regulating sequence (TRS)-dependent sgRNA was upregulated earlier in infection than TRS-independent sgRNA. An abundant class of TRS-independent sgRNA consisting of a portion of ORF1ab PROTEIN containing nsp1 HGNC joined to ORF10 PROTEIN ORF10 HGNC and 3UTR was upregulated at 48 hours post infection in human cell lines. We identified double-junction sgRNA containing both TRS-dependent and independent junctions. We found multiple sites at which the SARS-CoV-2 genome is consistently more modified than sgRNA, and that sgRNA modifications are stable across transcript clusters, host cells and time since infection. Our work highlights the dynamic nature of the SARS-CoV-2 transcriptome during its replication cycle. Our results are available via an interactive web-app at http://coinlab.mdhs.unimelb.edu.au/.

    Oligonucleotide Capture Sequencing of the SARS-CoV-2 Genome and Subgenomic Fragments from COVID-19 MESHD Individuals

    Authors: harshavardhan doddapaneni; Sara Javornik Cregeen; Richard Sucgang; Qingchang Meng; Xiang Qin; Vasanthi Avadhanula; Hsu Chao; Vipin Menon; Erin Nicholson; David Henke; Felipe-Andres Piedra; Anubama Rajan; Zeineen Momin; Kavya Kottapalli; Kristi L. Hoffman; Fritz J. Sedlazeck; Ginger Metcalf; Pedro A. Piedra; Donna M. Muzny; Joseph F. Petrosino; Richard A. Gibbs; Stephanie Erbar; Ferdia Bates; Diana Schneider; Bernadette Jesionek; Bianca Saenger; Ann-Kathrin Wallisch; Yvonne Feuchter; Hanna Junginger; Stefanie A. Krumm; Andre P. Heinen; Petra Adams-Quack; Julia Schlereth; Stefan Schille; Christoph Kroener; Ramon de la Caridad Gueimil Garcia; Thomas Hiller; Leyla Fischer; Rani S. Sellers; Shambhunath Choudhary; Olga Gonzalez; Fulvia Vascotto; Matthew R. Gutman; Jane Fontenot; Shannan Hall-Ursone; Kathleen Brasky; Matthew C Griffor; Seungil Han; Andreas A.H. Su; Joshua Lees; Nicole L. Nedoma; Ellene H. Mashalidis; Parag V. Sahasrabudhe; Charles Y. Tan; Danka Pavliakova; Guy Singh; Camila Fontes-Garfias; Michael Pride; Ingrid L. Scully; Tara Ciolino; Jennifer Obregon; Michal Gazi; Ricardo Carrion Jr.; Kendra J. Alfson; Warren V. Kalina; Deepak Kaushal; Pei-Yong Shi; Thorsten Klamp; Corinna Rosenbaum; Andreas N. Kuhn; Oezlem Tuereci; Philip R. Dormitzer; Kathrin U. Jansen; Ugur Sahin

    doi:10.1101/2020.12.11.421057 Date: 2020-12-11 Source: bioRxiv

    The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 MESHD ( COVID-19 MESHD). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected MESHD patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity and provided evidence of expression of ORF10 PROTEIN. Heterogeneous allelic frequencies along the 20kb ORF1ab PROTEIN gene suggested the presence of a defective interfering viral RNA species subpopulation in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.

    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.

    Variability of Accessory Proteins Rules the SARS-CoV-2 Pathogenicity

    Authors: Sk. Sarif Hassan; Pabitra Pal Choudhury; Vladimir N Uversky; Guy W. Dayhoff II; Alaa A. A. Aljabali; Bruce Uhal; Kenneth Lundstrom; Murat Seyran; Damiano Pizzol; Parise Adadi; Amos Lal; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-da-Cruz; Kazuo Takayama; Angel Serrano Aroca; Gaurav Chauhan; Giorgio Palu; Adam Brufsky

    doi:10.1101/2020.11.06.372227 Date: 2020-11-08 Source: bioRxiv

    The coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) which is pandemic with an estimated fatality rate less than 1% is ongoing. SARS-CoV-2 accessory proteins ORF3a PROTEIN, ORF6 PROTEIN, ORF7a PROTEIN, ORF7b PROTEIN, ORF8 PROTEIN, and ORF10 PROTEIN with putative functions to manipulate host immune mechanisms such as interferons, immune signaling receptor NLRP3 HGNC ( NOD HGNC-, LRR-, and pyrin domain-containing 3) inflammasome, inflammatory cytokines such as interleukin {beta} ( IL-1{beta HGNC}) are critical in COVID-19 MESHD pathology. Outspread variations of each of the six accessory proteins of all complete proteomes (available as of October 26, 2020, in the National Center for Biotechnology Information depository) of SARS-CoV-2, were observed across six continents. Across all continents, the decreasing order of percentage of unique variations in the accessory proteins was found to be ORF3a PROTEIN> ORF8 PROTEIN> ORF7a PROTEIN> ORF6 PROTEIN> ORF10 PROTEIN> ORF7b PROTEIN. The highest and lowest unique variations of ORF3a PROTEIN were observed in South America and Oceania, respectively. This finding suggests that the wide variations of accessory proteins seem to govern the pathogenicity of SARS-CoV-2, and consequently, certain propositions and recommendations can be made in the public interest.

    A theoretical analysis of the putative ORF10 PROTEIN protein in SARS-CoV-2

    Authors: Noah Avery Schuster; Claudia H Costa; Alessandra S Nunes; Isabel Bouzas; Tiago Ferreira; Vinicius M Porto; Danielle A Secco; - COVID-19 PPC group; Rogerio Rufino; Jean-Louis Mege; Jean-Marc Busnel; Joana Vitte

    doi:10.1101/2020.10.26.355784 Date: 2020-10-26 Source: bioRxiv

    Found just upstream of the 3'-untranslated region in the SARS-CoV-2 genome is the putative ORF10 PROTEIN which has been proposed to encode for the hypothetical ORF10 PROTEIN protein. Even though current research suggests this protein is not likely to be produced, further investigations into this protein are still warranted. Herein, this study uses multiple bioinformatic programs to theoretically characterize and construct the ORF10 PROTEIN protein in SARS-CoV-2. Results indicate this protein is mostly ordered and hydrophobic with high protein-binding propensity, especially in the N-terminus. Although minimal, an assessment of twenty-two missense mutations for this protein suggest slight changes in protein flexibility and hydrophobicity. When compared against two other protein models, this study's model was found to possess higher quality. As such, this model suggests the ORF10 PROTEIN protein contains a {beta}--{beta} motif with a {beta}-molecular recognition feature occurring as the first {beta}-strand. Furthermore, this protein also shares a strong phylogenetic relationship with other putative ORF10 PROTEIN protein's PROTEIN in closely related coronaviruses. Despite not yielding evidence for the existence of this protein within SARS-CoV-2, this study does present theoretical examinations that can serve as platforms to drive additional experimental work that assess the biological relevance of this hypothetical protein in SARS-CoV-2.

    Sequence Analysis for SNP Detection and Phylogenetic Reconstruction of SARS-CoV-2 Isolated from Nigerian COVID-19 MESHD Cases

    Authors: Idowu A. Taiwo; Nike Adeleye; Fatimah O. Anwoju; Adeyemi Adeyinka; Ijeoma C. Uzoma; Taiwo T. Bankole; Dianfan Li; Oliver F. Wirz; Kathryn E. Yost; Ji-Yeun Lee; Kelly Chun; Terri Wrin; Christos J. Petropoulos; Inyou Lee; Shannon Fallen; Paula M. Manner; Julie A. Wallick; Heather A. Algren; Kim M. Murray; Yapeng Su; Jennifer Hadlock; Joshua Jeharajah; William R. Berrington; George P. Pappas; Sonam T. Nyatsatsang; Alexander L. Greninger; Ansuman T. Satpathy; John S Pauk; Scott D. Boyd; James R. Heath

    doi:10.1101/2020.09.25.310078 Date: 2020-09-25 Source: bioRxiv

    Background: Coronaviruses are a group of viruses that belong to the Family Coronaviridae, Genus Betacoronavirus. In December 2019, a new coronavirus disease MESHD ( COVID-19 MESHD) characterized by severe respiratory symptoms was discovered. The causative pathogen was a novel coronavirus known as 2019-nCoV and later as SARS-CoV-2. Within two months of its discovery, COVID-19 MESHD became a pandemic causing widespread morbidity and mortality. Methodology: Whole genome sequence data of SARS-CoV-2 isolated from Nigerian COVID-19 MESHD cases were retrieved by downloading from GISAID database. A total of 18 sequences that satisfied quality assurance (length > 29700 nts and number of unknown bases denoted as N < 5%) were used for the study. Multiple sequence alignment (MSA) was done in MAFFT (Version 7.471) while SNP calling was implemented in DnaSP (Version 6.12.03) respectively and then visualized in Jalview (Version 2.11.1.0). Phylogenetic analysis was with MEGA X software. Results: Nigerian SARS-CoV-2 had 99.9% genomic similarity with four large conserved genomic regions. A total of 66 SNPs were identified out of which 31 were informative. Nucleotide diversity assessment gave Pi = 0.00048 and average SNP frequency of 2.22 SNPs per 1000 nts. Non-coding genomic regions particularly 5 UTR and 3 UTR had a SNP density of 3.77 and 35.4 respectively. The region with the highest SNP density was ORF10 PROTEIN with a frequency of 8.55 SNPs/1000 nts). Majority (72.2%) of viruses in Nigeria are of L lineage with preponderance of D614G mutation which accounted for 11 (61.1%) out of the 18 viral sequences. Nigeria SARS-CoV-2 revealed 3 major clades namely Oyo, Ekiti and Osun on a maximum likelihood phylogenetic tree. Conclusion and Recommendation: Nigerian SARS-CoV-2 reveals high mutation rate together with preponderance of L lineage and D614G mutants. Implication of these mutations for SARS-CoV-2 virulence MESHD and the need for more aggressive testing and treatment of COVID-19 MESHD in Nigeria is discussed. Additionally, attempt to produce testing kits for COVID-19 MESHD in Nigeria should consider the conserved regions identified in this study. Strict adherence to COVID-19 MESHD preventive measure is recommended in view of Nigerian SARS-CoV-2 phylogenetic clustering pattern, which suggests intensive community transmission possibly rooted in communal culture characteristic of many ethnicities in Nigeria.

    SARS-CoV-2 gene content and COVID-19 MESHD mutation impact by comparing 44 Sarbecovirus genomes

    Authors: Irwin Jungreis; Rachel Sealfon; Manolis Kellis

    doi:10.21203/rs.3.rs-80345/v1 Date: 2020-09-18 Source: ResearchSquare

    Despite its overwhelming clinical importance, the SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 MESHD biology. Here, we use comparative genomics to provide a high-confidence protein-coding gene set, characterize protein-level and nucleotide-level evolutionary constraint, and prioritize functional mutations from the ongoing COVID-19 pandemic MESHD. We select 44 complete Sarbecovirus genomes at evolutionary distances ideally-suited for protein-coding and non-coding element identification, create whole-genome alignments, and quantify protein-coding evolutionary signatures and overlapping constraint. We find strong protein-coding signatures for all named genes and for 3a, 6, 7a, 7b, 8, 9b, and also ORF3c, a novel alternate-frame gene. By contrast, ORF10 PROTEIN, and overlapping-ORFs 9c, 3b, and 3d lack protein-coding signatures or convincing experimental evidence and are not protein-coding. Furthermore, we show no other protein-coding genes remain to be discovered. Cross-strain and within-strain evolutionary pressures largely agree at the gene, amino-acid, and nucleotide levels, with some notable exceptions, including fewer-than-expected mutations in nsp3 HGNC and Spike subunit S1 PROTEIN, and more-than-expected mutations in Nucleocapsid. The latter also shows a cluster of amino-acid-changing variants in otherwise-conserved residues in a predicted B-cell epitope, which may indicate positive selection for immune avoidance. Several Spike-protein PROTEIN mutations, including D614G, which has been associated with increased transmission, disrupt otherwise-perfectly-conserved amino acids, and could be novel adaptations to human hosts. The resulting high-confidence gene set and evolutionary-history annotations provide valuable resources and insights on COVID-19 MESHD biology, mutations, and evolution.

    Mutational Analysis of SARS-CoV-2 Genome in African Population

    Authors: Olabode E. Omotoso; Ayoade Desmond Babalola; Amira Matareek; Lele Zhao; Virginia Ledda; Lucie Abeler- Dorner; Michelle Kendall; Anel Nurtay; Hao-Yuan Cheng; Ta-Chou Ng; Hsien-Ho Lin; Rob Hinch; Joanna Masel; A. Marm Kilpatrick; Christophe Fraser; Raquel Gonzalez Seoane; Clara Martinez Diago; Esther Canedo Carballeira; Macarena Alferez Alvarez Mallo; Cristina Casanova Pedraz; Onofre Alomar Mateu; Cristina Lesmes Heredia; Juan Carlos Wizner de Alva; Ruth Bernardo Vega; Montserrat Macia Badia; Cristina Alvarez Colomo; Antonio Sanchez Munoz; Laia Pratcorona Alicart; Ruben Alonso Saiz; Monica Lopez Rodriguez; Maria Carmen Barbancho Lopez; Marta Meca Casbas; Oscar Vaquerizo Ruiz; Eva Moran Antolin; Maria Jose Nunez Valera; Camino Fernandez Fernandez; Albert Tubau Navarra; Alejandra M Cano Garcia; Carmen Baena Luque; Susana Soldevilla Perez; Irene Gastaca Abasolo; Jose Adanez Garcia; Maria Teulon Gonzalez; Alberto Puertas Prieto; Rosa Ostos; Maria del Pilar Guadix Martin; Monica Catalina Coello; Maria Luisa De la Cruz Conti; Africa Cano Aguilar; Jose A Sainz Bueno

    doi:10.1101/2020.09.07.286088 Date: 2020-09-07 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly infectious and pathogenic virus has claimed lot of lives globally since its outbreak in December 2019 posing dire threat on public health, global economy, social and human interaction. At moderate rate, mutations in the SARS-CoV-2 genome are evolving which might have contributed to viral genome variability, transmission, replication efficiency and virulence in different regions of the world. The present study elucidated the mutational landscape in SARS-CoV-2 genome among the African population, which may have contributed to the virulence, pathogenicity and transmission observed in the region. Multiple sequence alignment of the SARS-CoV-2 genome (356 viral protein sequences) was performed using ClustalX version 2.1 and phylogenetic tree was built using Molecular Evolutionary Genetics Analysis (MEGA) X software. ORF1ab PROTEIN polyprotein, spike glycoprotein PROTEIN, ORF3 HGNC, ORF8 PROTEIN and nucleocapsid phosphoprotein were observed as mutational hotspots in the African population and may be of keen interest in the adaptability of SARS-CoV-2 to the human host. While, there is conservation in the envelope protein PROTEIN, membrane glycoprotein PROTEIN, ORF6 PROTEIN, ORF7a PROTEIN, ORF7b PROTEIN and ORF10 PROTEIN. The accumulation of moderate mutations (though slowly) in the SARS-CoV-2 genome as revealed in our study, could be a promising strategy to develop drugs or vaccines with respect to the viral conserved domains and host cellular proteins and/or receptors involved in viral invasion and replication to avoid a new viral wave due to drug resistance and vaccine evasion.

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MeSH Disease
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SARS-CoV-2 Proteins


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