Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (52)

ComplexRdRp (52)

NSP5 (18)

NSP3 (15)

ORF3a (8)


Filter

Genes
Diseases
SARS-CoV-2 Proteins
    displaying 11 - 20 records in total 52
    records per page




    Computational prediction of Carica papaya extracts as potential drug agents against RNA polymerase and Spike proteins PROTEIN of SARS-nCoV2 

    Authors: Rashid Saif; Muhammad Osama Zafar; Muhammad Hassan Raza; Talha Rehman; Saeeda Zia; Abdul Rasheed Qureshi

    doi:10.21203/rs.3.rs-105301/v1 Date: 2020-11-09 Source: ResearchSquare

    The emergence of COVID-19 MESHD outbreak caused by SARS-nCoV2 (S evere Acute Respiratory Syndrome MESHDnovel coronavirus 2), lead to the mass-scale mortalities around the world within a short span of time. The hour of the need is to develop the strategies and designing drugs/vaccines to control the spread of this contagion. In this paper, we predict the promising drug agents from the Carica papaya compounds by docking them with two major drug target proteins of S ARS- MESHDnCoV2, spike (7BZ5) and RNA-dependent RNA polymerase PROTEIN (7BW4). For this purpose, we used Molecular Operating Environment Software (MOE) for ligand-protein interactions and docking scores. Furthermore, we used PubChem, P DB MESHDand SwissADME web portals to retrieve ligands structures, proteins structures and to check Lipinski’s physiochemical parameters respectively. Cumulatively, this docking study has shown significant binding energies that (-4.2034 to -8.9013 Kcal/mol) indicates their potential against COVID-19 MESHD treatment. This study needs further evaluation on experimental basis.

    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.

    Different mutations in SARS-CoV-2 associate with severe and mild outcome

    Authors: Adam Nagy; Sandor Pongor; Balazs Gyorffy

    doi:10.1101/2020.10.16.20213710 Date: 2020-10-20 Source: medRxiv

    Introduction. Genomic alterations in a viral genome can lead to either better or worse outcome and identifying these mutations is of utmost importance. Here, we correlated protein-level mutations in the SARS-CoV-2 virus to clinical outcome. Methods. Mutations in viral sequences from the GISAID virus repository were evaluated by using hCoV-19/Wuhan/WIV04/2019 as the reference. Patient outcomes were classified as mild disease, hospitalization and severe disease ( death MESHD or documented treatment in an intensive-care unit). Chi-square test was applied to examine the association between each mutation and patient outcome. False discovery rate was computed to correct for multiple hypothesis testing and results passing a FDR cutoff of 5% were accepted as significant. Results. Mutations were mapped to amino acid changes for 2,120 non-silent mutations. Mutations correlated to mild outcome were located in the ORF8 PROTEIN, NSP6 PROTEIN, ORF3a PROTEIN, NSP4 PROTEIN NSP4 HGNC, and in the nucleocapsid phosphoprotein N. Mutations associated with inferior outcome were located in the surface ( S) glycoprotein PROTEIN, in the RNA dependent RNA polymerase PROTEIN, in the 3'-to5' exonuclease, in ORF3a PROTEIN, NSP2 HGNC NSP2 PROTEIN and N. Mutations leading to severe outcome with low prevalence were found in the surface ( S) glycoprotein PROTEIN and in NSP7 PROTEIN. Five out of 17 of the most significant mutations mapped onto a 10 amino acid long phosphorylated stretch of N indicating that in spite of obvious sampling restrictions the approach can find functionally relevant sites in the viral genome. Conclusions. We demonstrate that mutations in the viral genes may have a direct correlation to clinical outcome. Our results help to quickly identify SARS-CoV-2 infections MESHD harboring mutations related to severe outcome.

    Molecular characterization of SARS-CoV-2 from Bangladesh: Implications in genetic diversity, possible origin of the virus, and functional significance of the mutations

    Authors: Md Marufur Rahman; Shirmin Bintay Kader; S M Shahriar Rizvi; Zezhong Liu; Yingdan Wang; Die Luan; Kaiyue Wu; Zhigang Song; Tingting Sun; Yunping Ma; Yuanyuan Zhang; Qimin Wang; Xiang Li; Ping Ji; Yaning Li; Cheng Li; Yanling Wu; Tianlei Ying; Yumei Wen; Shibo Jiang; Tongyu Zhu; Lu Lu; Yongzheng Zhang; Qiang Zhou; Jinghe Huang; Auke C Reidinga; Daisy Rusch; Kim CE Sigaloff; Renee A Douma; Lianne de Haan; Egill A Fridgeirsson; Niels C Gritters van de Oever; Roger JMW Rennenberg; Guido van Wingen; Marcel JH Aries; Martijn Beudel; ítalo Karmann Aventurato; Mariana Rabelo de Brito; Marina Koutsodontis Machado Alvim; José Roberto da Silva Junior; Lívia Liviane Damião; Maria Ercilia de Paula Castilho Stefano; Iêda Maria Pereira de Sousa; Elessandra Dias da Rocha; Solange Maria Gonçalves; Luiz Henrique Lopes da Silva; Vanessa Bettini; Brunno Machado de Campos; Guilherme Ludwig; Rosa Maria Mendes Viana; Ronaldo Martins; Andre S. Vieira; José Carlos Alves-Filho; Eurico de Arruda Neto; Adriano Sebollela; Fernando Cendes; Fernando Q Cunha Sr.; André Damásio; Marco Aurélio Ramirez Vinolo; Carolina Demarchi Munhoz; Stevens K Rehen Sr.; Thais Mauad; Amaro Nunes Duarte-Neto; Luiz Fernando Ferraz da Silva; Marisa Dolhnikoff; Paulo Saldiva; Alexandre Todorovic Fabro; Alessandro S Farias; Pedro Manoel M. Moraes-Vieira; José Luiz Proença Módena; Clarissa Lin Yasuda; Marcelo A. Mori; Thiago Mattar Cunha; Daniel Martins-de-Souza

    doi:10.1101/2020.10.12.336099 Date: 2020-10-13 Source: bioRxiv

    In a try to understand the pathogenesis, evolution, and epidemiology of the SARS-CoV-2 virus, scientists from all over the world are tracking its genomic changes in real-time. Genomic studies can be helpful in understanding the disease dynamics. We have downloaded 324 complete and near-complete SARS-CoV-2 genomes submitted in the GISAID database from Bangladesh which were isolated between 30 March to 7 September 2020. We then compared these genomes with the Wuhan reference sequence and found 4160 mutation events including 2253 missense single nucleotide variations, 38 deletions, and 10 insertions. The C>T nucleotide change was most prevalent possibly due to selective mutation pressure to reduce CpG sites to evade CpG targeted host immune response. The most frequent mutation that occurred in 98% of the isolates was 3037C>T which is a synonymous change that almost always accompanied 3 other mutations that include 241C>T, 14408C>T (P323L in RdRp PROTEIN), and 23403A>G (D614G in spike protein PROTEIN). The P323L was reported to increase mutation rate and D614G is associated with increased viral replication and currently the most prevalent variant circulating all over the world. We identified multiple missense mutations in B-cell and T-cell predicted epitope regions and/or PCR target regions (including R203K and G204R that occurred in 86% of the isolates) that may impact immunogenicity and/or RT-PCR based diagnosis. Our analysis revealed 5 large deletion events in ORF7a PROTEIN and ORF8 PROTEIN gene products that may be associated with less severity of the disease and increased viral clearance. Our phylogeny analysis identified most of the isolates belonged to the Nextstrain clade 20B (86%) and GISAID clade GR (88%). Most of our isolates shared common ancestors either directly with European countries or jointly with middle eastern countries as well as Australia and India. Interestingly, the 19B clade (GISAID S clade) was unique to Chittagong which was originally prevalent in China. This reveals possible multiple introductions of the virus in Bangladesh via different routes. Hence more genome sequencing and analysis with related clinical data are needed to interpret the functional significance and better predict the disease dynamics that may be helpful for policymakers to control the COVID-19 MESHD COVID-19 MESHD pandemic in Bangladesh.

    SARS-CoV-2 has observably higher propensity to accept uracil as nucleotide substitution: Prevalence of amino acid substitutions and their predicted functional implications in circulating SARS-CoV-2 in India up to July, 2020

    Authors: Subrata Roy; Himadri Nath; Abinash Mallick; Subhajit Biswas; Noemi Manganaro; Giulia Piccini; Alessandro Manenti; Elisa Pantano; Anna Kabanova; Marco Troisi; Fabiola Vacca; Dario Cardamone; Concetta De Santi; Linda Benincasa; Chiara Agrati; Maria Rosaria Capobianchi; Concetta Castilletti; Arianna Emiliozzi; Massimiliano Fabbiani; Francesca Montagnani; Lorenzo Depau; Jlenia Brunetti; Luisa Bracci; Emanuele Montomoli; Claudia Sala; Giuseppe Ippolito; Rino Rappuoli

    doi:10.1101/2020.10.07.329771 Date: 2020-10-07 Source: bioRxiv

    SARS-CoV-2 has emerged as pandemic all over the world since late 2019. In this study, we investigated the diversity of the virus in the context of SARS-CoV-2 spread in India. Full-length SARS-CoV-2 genome sequences of the circulating viruses from all over India were collected from GISAID, an open data repository, until 25thJuly, 2020. We have focused on the non-synonymous changes across the genome that resulted in amino acid substitutions. Analysis of the genomic signatures of the non-synonymous mutations demonstrated a strong association between the time of sample collection and the accumulation of genetic diversity. Most of these isolates from India belonged to the A2a clade (63.4%) which has overcome the selective pressure and is spreading rapidly across several continents. Interestingly a new clade I/A3i has emerged as the second-highest prevalent type among the Indian isolates, comprising 25.5% of the Indian sequences. Emergence of new mutations in the S protein PROTEIN was observed. Major SARS-CoV-2 clades in India have defining mutations in the RdRp PROTEIN. Maximum accumulation of mutations was observed in ORF1a PROTEIN. Other than the clade-defining mutations, few representative non-synonymous mutations were checked against the available crystal structures of the SARS-CoV-2 proteins in the DynaMut server to assess their thermodynamic stability. We have observed that SARS-CoV-2 genomes contain more uracil than any other nucleotide. Furthermore, substitution of nucleotides to uracil was highest among the non-synonymous mutations observed. The A+U content in SARS-CoV-2 genome is much higher compared to other RNA viruses, suggesting that the virus RdRp PROTEIN has a propensity towards uracil incorporation in the genome. This implies that thymidine analogues may have a better chance to competitively inhibit SARS-CoV-2 RNA replication than other nucleotide analogues.

    Viroinformatics-based investigation of SARS-CoV-2 core proteins for potential therapeutic targets

    Authors: Lokesh Agrawal; Thanasis Poullikkas; Scott Eisenhower; Carlo Monsanto; Ranjith Kumar Bakku

    id:2009.12817v1 Date: 2020-09-27 Source: arXiv

    Due to SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) being a novel virus, there are currently no known effective antiviral drugs capable of slowing its progress. To accelerate the discovery of potential drug candidates, bioinformatics based in silico drug discovery can be applied as a very robust tool. In the present study, more than 60 antiviral drugs already available on the market, were chosen after literature survey. These can be used in clinical trials for the treatment of COVID-19 MESHD. In this study, these candidate drugs were ranked based on their potential to interact with the Spike protein PROTEIN and RdRp PROTEIN ( RNA-dependent RNA polymerase PROTEIN) of SARS-CoV-2. Additionally, the mechanism of their action as well as how the virus infection can utilize Hemoglobin to decrease the oxygen level in blood is explained. Moreover, multiple sequence alignments of the Spike protein PROTEIN with 75 sequences of different viruses from the Orthocoronavirinae subfamily were performed. This gives insight into the evolutionarily conserved domains that can be targeted using drug or antibody treatment. This multidimensional study opens a new layer of understanding about the most effective drug-targetable sites on the Spike protein PROTEIN of SARS-CoV-2.

    Ivermectin as a promising RNA-dependent RNA polymerase PROTEIN inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies

    Authors: Ananta Swargiary

    doi:10.21203/rs.3.rs-73308/v1 Date: 2020-09-07 Source: ResearchSquare

    Purpose: COVID-19 MESHD, caused by SARS-CoV2 virus is a contagious disease affecting millions of lives throughout the globe. Currently, there are no clinically approved drugs for SARS-CoV2 although some drugs are undergoing clinical trials. The present study investigates the binding property of ivermectin on four important drug targets, spike protein PROTEIN, RNA-dependent RNA polymerase PROTEIN, 3-chymotrypsin- and papain-like proteases PROTEIN of SARS-CoV2. Methods: The 3D structure of ivermectin along with known antiviral drug lopinavir, simeprevir and four nucleotides ATP, GTP, CTP, and UTP were downloaded from PubChem database. Crystal structures of proteins were downloaded from PDB database. PDB files were converted into pdbqt file using AutoDock tools. After proper processing and grid formation, docking was carried out in AutoDock vina. Furthermore, the co-crystallized RNA and its binding interactions with RdRp PROTEIN were studied using various visualization tools including Discovery studio.Results: Docking study showed that ivermectin is the best binding drug compared to lopinavir and simeprevir. The best binding interaction was found to be -9.7kcal/mol with RdRp PROTEIN suggesting potential inhibitor of the protein. Twenty-one amino acid residues of RdRp PROTEIN were found to interact with ivermectin including the catalytic residue Asp760. Furthermore, RNA- RdRp complex PROTEIN revealed that the catalytic active residues Ser759 and Asp760 of RdRp PROTEIN formed strong interactions with RNA chain. Binding of ivermectin in the active site of RdRp PROTEIN make clash with the nucleotides of RNA chain suggesting the possible inhibition of replication.Conclusions: The present study suggests ivermectin as a potential inhibitor of RdRp PROTEIN which may be crucial to combat the SARS-CoV2.

    Epidemiologically most successful SARS-CoV-2 variant: concurrent mutations in RNA-dependent RNA polymerase PROTEIN and spike protein PROTEIN

    Authors: Sten Ilmjärv; Fabien Abdul; Silvia Acosta-Gutiérrez; Carolina Estarellas; Ioannis Galdadas; Marina Casimir; Marco Alessandrini; Francesco Luigi Gervasio; Karl-Heinz Krause

    doi:10.1101/2020.08.23.20180281 Date: 2020-08-25 Source: medRxiv

    The D614G mutation of the Spike protein PROTEIN is thought to be relevant for SARS-CoV-2 infection MESHD. Here we report biological and epidemiological aspects of this mutation. Using pseudotyped lentivectors, we were able to confirm that the G614 variant of the Spike protein PROTEIN is markedly more infectious than the ancestral D614 variant. We demonstrate by molecular modelling that the replacement of aspartate by glycine in position 614 facilitates the transition towards an open state of the Spike protein PROTEIN. To understand whether the increased infectivity of the D614 variant explains its epidemiological success, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. There was no significant correlation between reported COVID mortality in different countries and the prevalence of the Wuhan versus G/L variant. However, when comparing the speed of emergence and the ultimate predominance in individual countries, the G/L variant displays major epidemiological supremacy. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN), is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2.

    Temporal landscape of mutation accumulation in SARS-CoV-2 genomes from Bangladesh: possible implications from the ongoing outbreak in Bangladesh

    Authors: Otun Saha; Rokaiya Nurani Shatadru; Nadira Naznin Rakhi; Israt Islam; Md. Shahadat Hossain; Md. Mizanur Rahaman; Leo C James; Madeline A Lancaster; Zhu Shu; Zhiming Yuan; Lei Tong; Han Xia; Jingzhe Pan; Natalie Garton; Manish Pareek; Michael Barer; Craig J Smith; Stuart M Allan; Michelle M. Lister; Hannah C. Howson-Wells; Edward C Holmes; Matthew W. Loose; Jonathan K. Ball; C. Patrick McClure; - The COVID-19 Genomics UK consortium study group; Shi Chen

    doi:10.1101/2020.08.20.259721 Date: 2020-08-21 Source: bioRxiv

    Along with intrinsic evolution, adaptation to selective pressure in new environments might have resulted in the circulatory SARS-CoV-2 strains in response to the geoenvironmental conditions of a country and the demographic profile of its population. Thus the analysis of genomic mutations of these circulatory strains may give an insight into the molecular basis of SARS-CoV-2 pathogenesis and evolution favoring the development of effective treatment and containment strategies. With this target, the current study traced the evolutionary route and mutational frequency of 198 Bangladesh originated SARS-CoV-2 genomic sequences available in the GISAID platform over a period of 13 weeks as of 14 July 2020. The analyses were performed using MEGA 7, Swiss Model Repository, Virus Pathogen Resource and Jalview visualization. Our analysis identified that majority of the circulating strains in the country belong to B and/or L type among cluster A to Z and strikingly differ from both the reference genome and the first sequenced genome from Bangladesh. Mutations in Nonspecific protein 2 ( NSP2 PROTEIN NSP2 HGNC), NSP3 PROTEIN NSP3 HGNC, RNA dependent RNA polymerase PROTEIN ( RdRp PROTEIN), Helicase HGNC, Spike, ORF3a PROTEIN, and Nucleocapsid (N) protein PROTEIN were common in the circulating strains with varying degrees and the most unique mutations(UM) were found in NSP3 HGNC NSP3 PROTEIN (UM-18). But no or limited changes were observed in NSP9 PROTEIN, NSP11 PROTEIN, E (Envelope), NSP7a, ORF 6, and ORF 7b suggesting the possible conserved functions of those proteins in SARS-CoV-2 propagation. However, along with D614G mutation, more than 20 different mutations in the Spike protein PROTEIN were detected basically in the S2 domain. Besides, mutations in SR-rich region of N protein PROTEIN and P323L in RDRP PROTEIN were also present. However, the mutation accumulation showed an association with sex and age of the COVID-19 MESHD positive cases. So, identification of these mutational accumulation patterns may greatly facilitate drug/ vaccine development deciphering the age and the sex dependent differential susceptibility to COVID-19 MESHD.

    In Silico Docking Analysis Revealed the Potential of Phytochemicals Present in Phyllanthus Amarus and Andrographis Paniculata, Used in Ayurveda Medicine in Inhibiting SARS-CoV-2

    Authors: Shridhar Hiremath; Vinay Kumar H D; Nandan M; Mantesh M; Shankarappa K S; Venkataravanappa V; Jahir Basha C R; C N Lakshminarayana Reddy

    doi:10.26434/chemrxiv.12751361.v1 Date: 2020-08-05 Source: ChemRxiv

    No therapeutics and vaccines are available against SARS-CoV-2 at present. In the current study we have made an attempt to provide preliminary evidences for interaction of 35 phytochemicals from two plants (Phyllanthus amarus and Andrographis paniculata used in Ayurveda) with SARS-CoV-2 proteins (S PROTEIN protein, 3CLpro PROTEIN, PLpro PROTEIN and RdRp PROTEIN) through in silico docking analysis. The docking was performed with the aid of AutoDock Vina and ADME and other pharmacokinetic properties were predicted using SWISSADME and admetSAR

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).
The web page can also be accessed via API.

Sources


Annotations

All
None
MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


Export subcorpus as...

This service is developed in the project nfdi4health task force covid-19 which is a part of nfdi4health.

nfdi4health is one of the funded consortia of the National Research Data Infrastructure programme of the DFG.