Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ORF1 (4)

ProteinN (3)

ProteinS (2)

ORF1ab (1)

ComplexRdRp (1)


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.

    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.

    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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