Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ORF1 (10)

ProteinN (5)

ORF1ab (3)

ComplexRdRp (3)

ProteinS (2)


SARS-CoV-2 Proteins
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    Systematic analysis of RNAi-accessible SARS-CoV-2 replication steps identifies ORF1 PROTEIN as promising target

    Authors: Shubhankar Ambike; Cho-Chin Cheng; Suliman Afridi; Martin Feuerherd; Philipp Hagen; Vincent Grass; Olivia Merkel; Andreas Pichlmair; Chunkyu Ko; Thomas Michler

    doi:10.21203/ Date: 2020-11-09 Source: ResearchSquare

    A promising approach to tackle the Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) could be small interfering (si)RNAs. The proof of concept that SARS-CoV-2 can be inhibited with siRNAs, however, is missing. Here, we report that siRNAs can target genomic RNA (gRNA) of SARS-CoV-2 after cell entry, terminating replication before start of transcription and preventing cytopathic effects. Coronaviruses replicate via negative sense intermediate transcripts using a unique discontinuous transcription process. As a result, each viral RNA contains identical sequences at the 5’ and 3’ end. Surprisingly, siRNAs were not active against intermediate negative sense transcripts. Targeting sequences shared by different viral transcripts allowed simultaneous suppression of gRNA and subgenomic (sg)RNAs by a single siRNA. The most effective suppression of viral replication and spread, however, was achieved by siRNAs targeting open reading frame 1 PROTEIN ( ORF1 PROTEIN) which is solely part of gRNA. We propose two independent mechanisms for this: An increased accessibility of translational-active ORF1 PROTEIN before the start of transcription, as well as highly abundant sgRNAs out-competing siRNAs that target common sequences of transcripts. Our work encourages the development of siRNA-based therapies for COVID-19 MESHD and suggests that an early therapy start, together with targeting ORF1 PROTEIN, might be key for high antiviral efficacy. 

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

    Authors: Jingzhi Lou; Shi Zhao; Lirong Cao; Zigui Chen; Renee WY Chan; Marc KC Chong; Benny CY Zee; Paul KS Chan; Maggie H Wang; Marian J Killip; Patricia A Cane; Christine B Bruce; Allen D.G Roberts; Guanghui Tian; Haji A. Aisa; Tianwen Hu; Daibao Wei; Yi Jiang; Gengfu Xiao; Hualiang Jiang; Leike Zhang; Xuekui Yu; Jingshan Shen; Shuyang Zhang; H. Eric Xu

    doi:10.1101/2020.11.01.363739 Date: 2020-11-02 Source: bioRxiv

    Background: During the pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD), the genetic mutations occurred in severe acute respiratory syndrome coronavirus 2 MESHD (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. Methods: Full-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 MESHD. Findings: Our results showed that the SARS-CoV-2 was in the process of continuous evolution, mainly involved in spike protein (S PROTEIN S protein HGNC), the RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) region of open reading frame 1 PROTEIN ( ORF1 PROTEIN) and nucleocapsid protein (N PROTEIN protein). By contrast, mutations in other proteins were sporadic and genetic distance to the initial sequenced strain did not show an increasing trend.

    SARS-CoV-2 genome-wide mapping of CD8 HGNC T cell recognition reveals strong immunodominance and substantial CD8 HGNC T cell activation in COVID-19 MESHD patients

    Authors: Sunil Kumar Saini; Ditte Stampe Hersby; Tripti Tamhane; Helle Rus Povlsen; Susana Patricia Amaya Hernandez; Morten Nielsen; Anne Ortved Gang; Sine Reker Hadrup; Sergio Poli; Lance M. Peter; Chase J. Taylor; Jessica B. Blackburn; Bradley W. Richmond; Andrew G. Nicholson; Doris Rassl; William A. Wallace; Ivan O. Rosas; R. Gisli Jenkins; Naftali Kaminski; Jonathan A. Kropski; Nicholas E. Banovich; - Human Cell Atlas Lung Biological Network; Renata J Medeiros; Juliana MM Gomes; Mara Souza Junqueira; Katia Conceicao; Leticia G. Pontes; Antonio Condino Neto; Andrea C Perez; Leonardo G Barcellos; Jose Dias Correa Junior; Erick Gustavo Dorlass; Niels OS Camara; Edison Luiz Durigon; Fernando Q Cunha; Rafael H Nobrega; Glaucia M Machado-Santelli; Chuck S Farah; Flavio P Veras; Jorge Galindo-Villegas; Leticia Costa-Lotufo; Thiago M Cunha; Roger Chammas; Luciani R. Carvalho; Cristiane R. Guzzo; Ives Charlie-Silva

    doi:10.1101/2020.10.19.344911 Date: 2020-10-19 Source: bioRxiv

    To understand the CD8 HGNC+ T cell immunity related to viral protection and disease severity in COVID-19 MESHD, we evaluated the complete SARS-CoV-2 genome (3141 MHC-I binding peptides) to identify immunogenic T cell epitopes, and determine the level of CD8 HGNC+ T cell involvement using DNA-barcoded peptide-major histocompatibility complex (pMHC) multimers. COVID-19 MESHD patients showed strong T cell responses, with up to 25% of all CD8 HGNC+ lymphocytes specific to SARS-CoV-2-derived immunodominant epitopes, derived from ORF1 PROTEIN ( open reading frame 1 PROTEIN), ORF3 HGNC, and Nucleocapsid (N) protein PROTEIN. A strong signature of T cell activation was observed in COVID-19 MESHD patients, while no T cell activation was seen in the non-exposed and high exposure risk healthy donors. Interestingly, patients with severe disease displayed the largest T cell populations with a strong activation profile. These results will have important implications for understanding the T cell immunity to SARS-CoV-2 infection MESHD, and how T cell immunity might influence disease development.

    Saliva as a potential clinical specimen for diagnosis of SARS-CoV-2

    Authors: Dr. Debdutta Bhattacharya; Dr. Debaprasad Parai; Usha Kiran Rout; Rashmi Ranjan Nanda; Dr. Srikanta Kanungo; Dr. Girish Chandra Dash; Dr. Subrat Kumar Palo; Dr. Siddharth Giri; Hari Ram Choudhary; Dr. Jaya Singh Kshatri; Dr. Jyotirmayee Turuk; Dr. Bijay Mishra; Dr. Saroj Dash; Dr. Sanghamitra Pati

    doi:10.1101/2020.09.11.20192591 Date: 2020-09-11 Source: medRxiv

    Background It is almost nine months, still there is no sign to stop the spreading of the COVID-19 pandemic MESHD COVID-19 pandemic MESHD. Rapid and early detection of the virus is the master key to cease the rapid spread and break the human transmission chain. There are very few studies in search of an alternate and convenient diagnostic tool which can substitute nasopharyngeal swab (NPS) specimen for detection of SARS-CoV-2. We aimed to analyse the comparison and agreement between the feasibility of using the saliva in comparison to NPS for diagnosis of SARS-CoV-2. Methods A total number of 74 patients were enrolled for this study. We analysed and compared the NPS and saliva specimen collected within 48 h after the symptom onset. We used real time quantitative polymerase chain reaction (RT-qPCR), gene sequencing for the detection and determination SARS-CoV-2 specific genes. Phylogenetic tree was constructed to establish the isolation of viral RNA from saliva. We use Bland-Altman model to identify the agreement between two sampling methods. Findings This study shows a lower CT mean value for the detection of SARS-CoV-2 ORF1 PROTEIN gene (27.07; 95% CI, 25.62 to 28.52) in saliva methods than that of NPS (28.24; 95% CI, 26.62 to 29.85) sampling method. Bland-Altman analysis produces relatively smaller bias and high agreement between these specimen tools. Phylogenetic analysis with the RdRp PROTEIN and Spike gene confirmed the presence of SARS-CoV-2 in the saliva samples. Interpretation: In conclusion, our study highlights that saliva represents a promising tool in COVID-19 MESHD diagnosis and would reduce the exposure risk of frontline health workers which is one of biggest concern in primary healthcare settings.

    Design and clinical validation of a 3D-printed nasopharyngeal swab for COVID-19 MESHD testing

    Authors: Joshua K Tay; Gail B Cross; Chun Kiat Lee; Benedict Yan; Jerold Loh; Zhen Yu Lim; Nicholas Ngiam; Jeremy Chee; Soo Wah Gan; Anmol Saraf; Wai Tung Eason Chow; Han Lee Goh; Chor Hiang Siow; Derrick WQ Lian; Woei Shyang Loh; Kwok Seng Loh; Vincent TK Chow; De Yun Wang; Jerry YH Fuh; Ching-Chiuan Yen; John EL Wong; David M Allen

    doi:10.1101/2020.06.18.20134791 Date: 2020-06-20 Source: medRxiv

    We describe the development and validation of a novel 3D-printed nasopharyngeal swab for the identification of SARS-CoV-2. We subjected the novel swab to mechanical and fluid absorption testing ex-vivo, and confirmed its ability to retain and release murine coronavirus and SARS-CoV-2. Compared to the Copan FLOQSwab, the novel swab displayed excellent correlation of RT-PCR cycle threshold values on paired clinical testing in COVID-19 MESHD patients, at r = 0.918 and 0.943 for the SARS-CoV-2 ORF1 PROTEIN/a and sarbecovirus E-gene PROTEIN respectively. Overall positive and negative percent agreement was 90.6% and 100% respectively on a dual-assay RT-PCR platform, with discordant samples observed only at high cycle thresholds. When carefully designed and tested, 3D-printed swabs are a viable alternative to traditional swabs and will help mitigate strained resources in the escalating COVID-19 pandemic MESHD.

    Broad and strong memory CD4 HGNC+ and CD8 HGNC+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 MESHD patients.

    Authors: Tao Dong; Yanchun Peng; Alexander J Mentzer; Guihai Liu; Xuan Yao; Zixi Yin; Danning Dong; Wanwisa Dejnirattisai; Lance Turtle; Timothy Rostron; Krishanthi Subramaniam; Paul Thomson; Ping Zhang; Christina Dold; Jeremy Ratcliff; Thushan de Silva; Paul Sopp; Dannielle Wellington; Ushani Rajapaksa; Wayne Paes; Persephone Borrow; Benedikt M Kessler; Jeremy W Fry; Nikolai F Schwabe; Malcolm G Semple; J Kenneth Baillie; Peter JM Openshaw; Richard J Cornall; Chris Conlon; Gavin Screaton; Paul Klenerman; Juthathip Mongkolsapaya; Andrew McMichael; Julian C Knight; Graham Ogg; Peter Simmonds; Teresa Lockett; Robert Levin; Shona C Moore; Mariolina Salio; Giorgio Napolitani; Yi-Ling Chen; Susie Dunachie; Piyada Supasa; Chang Liu; Cesar Lopez-Camacho; Jose Slon-Campos; Yuguang Zhao; David I Stuart; Guido Paeson; Jonathan Grimes; Fred Antson; Oliver W Bayfield; Dorothy EDP Hawkins; De-Sheng Ker; Azim Ansari; Ellie Barnes; John Frater; Georgina Kerr; Philip Goulder

    doi:10.1101/2020.06.05.134551 Date: 2020-06-08 Source: bioRxiv

    COVID-19 MESHD is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19 MESHD, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFN{gamma} based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1 PROTEIN. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 MESHD were significantly higher in severe compared to mild COVID-19 MESHD cases, and this effect was most marked in response to spike, membrane, and ORF3a PROTEIN proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti- Nucleoprotein PROTEIN (NP) endpoint antibody titre (p<0.001, <0.001 and =0.002). We identified 39 separate peptides containing CD4 HGNC+ and/or CD8 HGNC+ epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M PROTEIN, 32%, 47%) and one in the nucleoprotein PROTEIN (Np, 35%). CD8 HGNC+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory MESHD phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8 HGNC+ T cells than spike-specific CD8 HGNC+ T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8 HGNC+ to CD4 HGNC+ T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections MESHD. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non- spike proteins PROTEIN within future COVID-19 MESHD vaccine design.

    Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals

    Authors: Nina Le Bert; Anthony Tanoto Tan; Kamini Kunasegaran; Christine Y. L. Tham; Morteza Hafezi; Adeline Chia; Melissa Chng; Meiyin Lin; Nicole Tan; Martin Linster; Wan Ni Chia; Mark I-Cheng Chen; Lin-Fa Wang; Eng Eong Ooi; Shirin Kalimuddin; Paul Anantharajal Tambyah; Jenny Guek-Hong Low; Yee-Joo Tan; Antonio Bertoletti

    doi:10.1101/2020.05.26.115832 Date: 2020-05-27 Source: bioRxiv

    Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural ( nucleocapsid protein PROTEIN, NP) and non-structural (NSP-7 and NSP13 PROTEIN of ORF1 PROTEIN) regions of SARS-CoV-2 in convalescent from COVID-19 MESHD (n=24). In all of them we demonstrated the presence of CD4 HGNC and CD8 HGNC T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 MESHD or contact with SARS/ COVID-19 MESHD patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 PROTEIN and 13, which were rarely detected in COVID-19 MESHD- and SARS-recovered patients. Epitope characterization of NSP7 PROTEIN-specific T cells showed recognition of protein fragments with low homology to "common cold" human coronaviruses but conserved among animal betacoranaviruses. Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection MESHD is of paramount importance for the management of the current COVID-19 pandemic MESHD.

    Translation-associated mutational U-pressure in the first ORF of SARS-CoV-2 and other coronaviruses

    Authors: Vladislav Victorovich Khrustalev; Rajanish Giri; Tatyana Aleksandrovna Khrustaleva; Shivani Krishna Kapuganti; Aleksander Nicolaevich Stojarov; Victor Vitoldovich Poboinev

    doi:10.1101/2020.05.05.078238 Date: 2020-05-05 Source: bioRxiv

    Within four months of the ongoing COVID-19 pandemic MESHD COVID-19 pandemic MESHD caused by SARS-CoV-2, more than 250 nucleotide mutations have been detected in the ORF1 PROTEIN of the virus isolated from different parts of the globe. These observations open up an obvious question about the rate and direction of mutational pressure for further vaccine and therapeutics designing. In this study, we did a comparative analysis of ORF1a PROTEIN and ORF1b by using the first isolate (Wuhan strain) as the parent sequence. We observed that most of the nucleotide mutations are C to U transitions. The rate of synonymous C to U transitions is significantly higher than the rate of nonsynonymous ones, indicating negative selection on amino acid substitutions. Further, trends in nucleotide usage bias have been investigated in 49 coronaviruses species. A strong bias in nucleotide usage in fourfold degenerated sites towards uracil residues is seen in ORF1 PROTEIN of all the studied coronaviruses. A more substantial mutational U pressure is observed in ORF1a PROTEIN than in ORF1b owing to the translation of ORF1ab PROTEIN via programmed ribosomal frameshifting. Unlike other nucleotide mutations, mutational U pressure caused by cytosine deamination, mostly occurring in the RNA-plus strand, cannot be corrected by the proof-reading machinery of coronaviruses. The knowledge generated on the direction of mutational pressure during translation of viral RNA-plus strands has implications for vaccine and nucleoside analogue development for treating covid-19 MESHD and other coronavirus infections MESHD.

    Specific mutations in SARS-CoV2 RNA dependent RNA polymerase PROTEIN and helicase HGNC alter protein structure, dynamics and thus function: Effect on viral RNA replication


    doi:10.1101/2020.04.26.063024 Date: 2020-04-27 Source: bioRxiv

    1.The open reading frame PROTEIN (ORF) 1ab of SARS-CoV2 encodes non-structural proteins involved in viral RNA functions like translation and replication including nsp1-4; 3C like proteinase; nsp6-10; RNA dependent RNA polymerase PROTEIN ( RdRp PROTEIN); helicase HGNC and 3-5 exonuclease. Sequence analyses of ORF1ab PROTEIN unravelled emergence of mutations especially in the viral RdRp PROTEIN and helicase HGNC at specific positions, both of which are important in mediating viral RNA replication. Since proteins are dynamic in nature and their functions are governed by the molecular motions, we performed normal mode analyses of the SARS-CoV2 wild type and mutant RdRp PROTEIN and helicases to understand the effect of mutations on their structure, conformation, dynamics and thus function. Structural analyses revealed that mutation of RdRp PROTEIN (at position 4715 in the context of the polyprotein/ at position 323 of RdRp PROTEIN) leads to rigidification of structure and that mutation in the helicase HGNC (at position 5828 of polyprotein/ position 504) leads to destabilization increasing the flexibility of the protein structure. Such structural modifications and protein dynamics alterations might alter unwinding of complex RNA stem loop structures, the affinity/ avidity of polymerase RNA interactions and in turn the viral RNA replication. The mutation analyses of proteins of the SARS-CoV2 RNA replication complex would help targeting RdRp PROTEIN better for therapeutic intervention.

    Comparative analysis of primer-probe sets for the laboratory confirmation of SARS-CoV-2

    Authors: Yu Jin Jung; Gun-Soo Park; Jun Hye Moon; Keunbon Ku; Seung-Hwa Beak; Seil Kim; Edmond Changkyun Park; Daeui Park; Jong-Hwan Lee; Cheol Woo Byeon; Joong Jin Lee; Jin-soo Maeng; Seong Jun Kim; Seung Il Kim; Bum-Tae Kim; Min Jun Lee; Hong Gi Kim

    doi:10.1101/2020.02.25.964775 Date: 2020-02-27 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is newly emerging human infectious diseases MESHD, which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2, also previously known as 2019-nCoV). Within two months of the outbreak, more than 80,000 cases of COVID-19 MESHD have been confirmed worldwide. Since the human to human transmission occurred easily and the human infection is rapidly increasing, the sensitive and early diagnosis is essential to prevent the global outbreak. Recently, World Health Organization (WHO) announced various primer and probe sets for SARS-CoV-2 previously developed in China, Germany, Hong Kong, Japan, Thailand, and USA. In this study, we compared the ability to detect SARS-CoV-2 RNA among the seven primer-probe sets for N gene PROTEIN and the three primer-probe sets for Orf1 PROTEIN gene. The result of the comparative analysis represented that the 2019-nCoV_N2, N3 of USA and the ORF1ab PROTEIN of China are the most sensitive primer-probe sets for N and Orf1 PROTEIN genes, respectively. Therefore, the appropriate combination from ORF1ab PROTEIN (China), 2019-nCoV_N2, N3 (USA), and NIID_2019-nCOV_N (Japan) sets should be selected for the sensitive and reliable laboratory confirmation of SARS-CoV-2.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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