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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (15)

ProteinS (8)

ComplexRdRp (7)

NSP3 (7)

ORF3a (5)


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SARS-CoV-2 Proteins
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    Comparative analysis of loop-mediated isothermal amplification (LAMP)-based assays for rapid detection of SARS-CoV-2 genes

    Authors: Daniel Urrutia-Cabrera; Roxanne Hsiang-Chi Liou; Jianxiong Chan; Sandy Shen-Chi Hung; Alex W Hewitt; Keith Martin; Patrick Kwan; Raymond Ching-Bong Wong

    doi:10.1101/2020.12.21.20248288 Date: 2020-12-22 Source: medRxiv

    The COVID-19 pandemic MESHD caused by SARS-CoV-2 has infected millions worldwide and there is an urgent need to increase our diagnostic capacity to identify infected cases. Although RT-qPCR remains the gold standard for SARS-CoV-2 detection, this method requires specialised equipment in a diagnostic laboratory and has a long turn-around time to process the samples. To address this, several groups have recently reported development of loop-mediated isothermal amplification (LAMP) as a simple, low cost and rapid method for SARS-CoV-2 detection. Herein we present a comparative analysis of three LAMP-based assays that target different regions of the SARS-CoV-2: ORF1ab PROTEIN RdRP PROTEIN, ORF1ab PROTEIN nsp3 HGNC and Gene N PROTEIN. We perform a detailed assessment of their sensitivity, kinetics and false positive rates for SARS-CoV-2 diagnostics in LAMP or RT-LAMP reactions, using colorimetric or fluorescent detection. Our results independently validate that all three assays can detect SARS-CoV-2 in 30 minutes, with robust accuracy at detecting as little as 1000 RNA copies and the results can be visualised simply by color changes. We also note the shortcomings of these LAMP-based assays, including variable results with shorter reaction time or lower load of SARS-CoV-2, and false positive results in some experimental conditions. Overall for RT-LAMP detection, the ORF1ab PROTEIN RdRP PROTEIN and ORF1ab PROTEIN nsp3 HGNC assays have higher sensitivity and faster kinetics for detection, whereas the Gene N PROTEIN assay exhibits no false positives in 30 minutes reaction time. This study provides validation of the performance of LAMP-based assays for SARS-CoV-2 detection, which have important implications in development of point-of-care diagnostic for SARS-CoV-2.

    Mapping the Non-Structural Transmembrane Proteins of SARS-CoV-2

    Authors: Sunil Thomas

    id:10.20944/preprints202012.0366.v1 Date: 2020-12-15 Source: Preprints.org

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the disease COVID-19 MESHD has wreaked havoc on the health and economy of humanity. In addition, the disease is observed in domestic and wild animals. The disease has impacted directly and indirectly every corner of the planet. Currently, there are no vaccines and effective therapies for COVID-19 MESHD. SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome of 29.8 kb. More than two-thirds of the genome comprises Orf1ab encoding 16 non-structural proteins (nsps) followed by mRNAs encoding structural proteins, spike (S PROTEIN), envelop (E), membrane (M), and nucleocapsid (N PROTEIN). These genes are interspaced with several accessory genes (open reading frames [Orf] 3a, 3b, 6, 7a, 7b, 8, 9b, 9c and 10). The functions of these proteins are of particular interest for understanding the pathogenesis of SARS-CoV-2. Several of the nsps ( nsp3 HGNC, nsp4 HGNC, nsp6) and Orf3a PROTEIN are transmembrane proteins involved in regulating the host immunity, modifying host cell organelles for viral replication and escape and hence considered drug targets. In this paper we report mapping the transmembrane structure of the non-structural proteins of SARS-CoV-2.

    DeepNEU: a Machine Learning Stem Cell simulation platform for evaluating the impact of Loss of Function and Gain of Function mutations in the SARS-CoV-2 genome

    Authors: Sally Esmail; Wayne R Danter

    doi:10.21203/rs.3.rs-116683/v1 Date: 2020-11-26 Source: ResearchSquare

    The global pandemic caused by the SARS-C0V-2 virus continues to spread. Infection with the SARS-CoV-2 causes a disease of variable severity known as COVID-19 MESHD. It is certain that the viral genome has already mutated and will continue to mutate in unknown directions. These mutations can (1) have no significant impact (they are silent), result in (2) a loss of virulence/function (LOF) or (3) a gain in virulence/function (GOF). Research involving GOF mutations remain especially controversial and highly regulated because accidental release or misuse of a more lethal virus could have catastrophic global effects.The primary purpose of this project was to evaluate the ability of the DeepNEU machine learning stem-cell simulation platform to enable rapid and efficient assessment of the impact of viral LOF and GOF mutations on SARS-CoV-2 virulence. The data generated from this project confirm that (1) SARS-CoV-2 infection MESHD can be simulated in human alveolar type lung MESHD cells, (2) these simulated infected lung cells can be used to assess the impact of LOF and GOF mutations in a viral genome, (3) a new and simple four-factor virulence measure, the DeepNEU Case Fatality Rate (dnCFR) based on NSP3 PROTEIN NSP3 HGNC, Spike-RDB MESHD, N protein PROTEIN and M protein PROTEIN can be used to assess the impact of LOF and GOF mutations and (4) the platform combined with the dnCFR measure successfully identified specific and potentially beneficial mutations (LOF) as well as deleterious mutations (GOF) that potentially increase the virulence of the SARS-CoV-2 virus. We conclude that the DeepNEU platform and the dnCFR measure should be urgently developed, further validated and applied to SARS-CoV-2 and other viral pathogens as important tools for future pandemic preparedness.

    In Silico studies of Natural compounds that inhibit SARS-CoV-2 Nucleocapsid Nsp1 HGNC/ Nsp3 HGNC proteins mediated Viral Replication and Pathogenesis

    Authors: Hemanth Kumar Manikyam

    doi:10.21203/rs.3.rs-103400/v1 Date: 2020-11-05 Source: ResearchSquare

    Highly Transmissible and pathogenic coronavirus that emerged in late December of 2019 caused Severe acute respiratory syndrome MESHD (SARS-CoV-2), which challenged human health and public safety. Severity of the disease depends on the viral load and the type of mutation that occurred in the coronavirus. Nonstructural proteins like, Nsp1 HGNC, Nsp3 HGNC, Nsp12 and Nsp13 including other viral proteins plays important role during viral replication life cycle. Viral Replication initiated by hacking the host cellular mechanism either by synergy or by suppression using nucleocapsid proteins PROTEIN of the virus. Spike (S) protein PROTEIN of the SARS-CoV-2 uses angiotensin-converting enzyme II ( ACE2 HGNC) and TRMPSS as a cell entry. Once virus enters host cell, nucleocapsid proteins PROTEIN along with its genome is releases from endosomes into cytosol of the host cell. Ca2+/ CaM HGNC ( Calmodulin HGNC)/Calcineurin complex of the host cell plays important role during viral replication which is mediated by nucleocapsid proteins PROTEIN of the virus. Nsp1 HGNC/ Nsp3 HGNC nonstructural proteins triggers synergetic activity with CD147 HGNC/ CyPA HGNC/ HSPG HGNC pathway and TRMP2/ADPr/Ca+2 mediated Ca2+/CaM ( Calmodulin HGNC)/Calcineurin synthesis and free radicle generation in mitochondria leading to viral replication and severe chemokine activation pathways. Docking studies were carried out to inhibit Cyclophilin A and TRMP2 proteins as drug targets. Natural compounds like Withanolide A, Columbin, Cucurbitacin E, Boswellic acid along with Cyclosporines, Vitamin E and N-Acetyl cysteine ( NAC HGNC) were selected as ligands to study docking studies. Withanolide A and Cyclosporines had shown good inhibition activity against Cyclophilin A, whereas Columbin, Boswellic acid, Cucurbitacin E, Vitamin E and N-Acetyl cysteine ( NAC HGNC) had shown inhibitory activity against TRMP2. Thus, we suggest conducting further studies to conclude above pathways mechanism and inhibitory effect of natural compounds against the Nsp1 HGNC/ Nsp3 HGNC mediated pathways Invitro and In vivo.

    Emergence of Novel SARS-CoV-2 Variants in the Netherlands

    Authors: Aysun Urhan; Thomas Abeel

    doi:10.1101/2020.11.02.20224352 Date: 2020-11-04 Source: medRxiv

    In this study, we analyzed SARS-CoV-2 genomes in the Netherlands, in the context of global viral population since the beginning of the pandemic. We have identified the most variant sites on the whole genome as well as the stable, conserved ones on the S and N proteins PROTEIN. We found four mutations, S:D614G, NSP12b:P314L, NSP3 HGNC NSP3 PROTEIN:F106F, to be the most frequent ones that dominate the SARS-CoV-2 population outside of China. We detected novel variants of SARS-CoV-2 almost unique to the Netherlands that form localized clusters, indicating community spread. We emphasize that while SARS-CoV-2 is evolving, and the number of mutations from the reference sequence is increasing, we observe only little diversity in the new variants as we enter the later stages of the pandemic. Our analyses suggest we have diverged away from the current SARS-CoV-2 reference enough that the reference should be re-evaluated to represent the current viral population more accurately. We assert our work provides valuable information on the genetic diversity of SARS-CoV-2 and its local dynamics in the Netherlands, especially for DNA-based diagnostic, therapeutic or vaccine development against COVID-19 MESHD. We suggest sequence-based analyses should opt for a consensus representation to adequately cover the genomic variation observed.

    Potential Achilles heels of SARS-CoV-2 displayed by the base order-dependent component of RNA folding energy

    Authors: Chiyu Zhang; Jana De Vrieze; Angela Choi; Raveen Rathnasinghe; Gabriel Laghlali; Annemiek Uvyn; Simon Van Herck; Lutz Nuhn; Kim Deswarte; Zifu Zhong; Niek Sanders; Stefan Lienenklaus; Sunil David; Shirin Strohmeier; Fatima Amanat; Florian Krammer; Hamida Hammad; Bart N Lambrecht; Lynda Coughlan; Adolfo Garcia-Sastre; Bruno G De Geest; Michael Schotsaert; Marion Yger; Bertrand Degos; Louise-Laure Mariani; Christophe Bouche; Nathalie Dzierzynski; Bruno Oquendo; Flora Ketz; An-Hung Nguyen; Aurelie Kas; Jean-Yves Delattre; Jean-Christophe Corvol

    doi:10.1101/2020.10.22.343673 Date: 2020-10-23 Source: bioRxiv

    The energetics of the folding of a single-stranded nucleic acid into a stem-loop structure depend on both the composition and order of its bases. Composition tends to reflect genome-wide evolutionary pressures. Order better reflects local pressures. Base order is likely to be conserved when encoding a function critical for survival. The base order-dependent component of the folding energy has shown that a highly conserved region in HIV-1 genomes associates with an RNA structure. This corresponds to a packaging signal that is specifically recognized by the nucleocapsid domain of the Gag polyprotein HGNC. Long viewed as a potential HIV-1 "Achilles heel," the signal can be targeted by a recently described antiviral compound (NSC 260594) or by synthetic oligonucleotides. Thus, a conserved base-order-rich region of HIV-1 may facilitate therapeutic attack. Although SARS-CoV-2 differs in many respects from HIV-1, the same technology displays regions with a high base order-dependent folding energy component, which are also highly conserved. This indicates structural invariance (SI) sustained by natural selection. While the regions are often also protein-encoding (e.g. NSP3 HGNC NSP3 PROTEIN, ORF3a PROTEIN), we suggest that their nucleic acid level functions, such as the ribosomal frameshifting element (FSE) that facilitates differential expression of 1a and 1ab polyproteins, can be considered potential "Achilles heels" for SARS-CoV-2 that should be susceptible to therapies like those envisaged for AIDS MESHD. The region of the FSE scored well, but higher SI scores were obtained in other regions, including those encoding NSP13 PROTEIN and the nucleocapsid (N) protein PROTEIN.

    Drug Design and Repurposing with DockThor-VS Web Server: Virtual Screening focusing on SARS-CoV-2 Therapeutic Targets and their Non-Synonym Variants

    Authors: Isabella A. Guedes; Leon S. C. Costa; Karina B. dos Santos; Ana L. M. Karl; Gregório K. Rocha; Iury M. Teixeira; Marcelo M. Galheigo; Vivian Medeiros; Eduardo Krempser; Fábio L. Custódio; Helio J. C. Barbosa; Marisa F. Nicolás; Laurent E. Dardenne

    doi:10.21203/rs.3.rs-96789/v1 Date: 2020-10-22 Source: ResearchSquare

    The COVID-19 MESHD caused by the SARS-CoV-2 virus was declared as a pandemic disease in March 2020 by the World Health Organization (WHO). Structure-Based Drug Design strategies based on docking methodologies have been widely used for both new drug development and drug repurposing to find effective treatments against this disease. In this work, we present the developments implemented in the DockThor-VS web server to provide a virtual screening (VS) platform with curated structures of potential therapeutic targets from SARS-CoV-2 incorporating genetic information regarding relevant non-synonymous variations. The web server facilitates repurposing VS experiments providing curated libraries of currently available drugs on the market. Currently, DockThor-VS provides ready-for-docking 3D structures for wild type and selected mutations for Nsp3 HGNC (papain-like, PLpro PROTEIN domain), Nsp5 HGNC ( Mpro PROTEIN, 3CLpro PROTEIN), Nsp12 ( RdRp PROTEIN), Nsp15 (NendoU), N protein PROTEIN and Spike. We performed VS experiments of FDA-approved drugs considering the therapeutic targets available at the web server to assess the impact of considering different structures and mutations in the identification of possible new treatments of SARS-CoV-2 infections MESHD. The DockThor-VS is freely available at www.dockthor.lncc.br.

    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.

    Dynamic tracking of variant frequencies depicts the evolution of mutation sites amongst SARS-CoV-2 genomes from India

    Authors: Gaurav Sharma; Vaishnavi Kolte; Shenu Hudson B.; Azra Khan

    doi:10.1101/2020.07.14.201905 Date: 2020-07-14 Source: bioRxiv

    With the exponential spread of COVID-19 MESHD COVID-19 MESHD pandemic across the world within the last six months, SARS-CoV-2 strains are continuously trying to adapt themselves in their host environment by random mutations. While doing so, some variants with evolutionary advantages such as better human to human transmissibility potential should get naturally selected. This short communication demonstrates how the mutation probability patterns are evolving in 864 SAR-CoV-2 strains isolated from COVID-19 MESHD patients across diverse Indian states. We have identified 30 such variants showing contrasting mutational probabilities in the span of four months. Out of these, the mutational probabilities of 25 variants including C14408T (in RdRp PROTEIN gene), A23403G (in spike gene), C6312A ( nsp3 HGNC gene) are continuously increasing suggesting that these mutations are being propagated with time due to their unexplored evolutionary advantages. In contrast, the mutational probabilities of five variants including C6312A ( nsp3 HGNC gene), G11083T (nsp6 gene), C28311T ( N gene PROTEIN) have significantly decreased in May-June as compared to March-April, suggesting these mutations are being terminated with time. Further in-depth investigation of these identified variants will provide valuable knowledge about the evolution, infection strategies, transmission rates, and epidemiology of SARS-CoV-2 in India.

    A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 MESHD Patients

    Authors: Dharmendra Kumar Maurya

    doi:10.26434/chemrxiv.12630539.v1 Date: 2020-07-09 Source: ChemRxiv

    The current outbreak of the corona virus disease 2019 ( COVID-19 MESHD), has affected almost entire world and become pandemic now. Currently, there is neither any FDA approved drugs nor any vaccines available to control it. Very recently in Bangladesh, a group of doctors reported astounding success in treating patients suffering from COVID-19 MESHD with two commonly used drugs, Ivermectin and Doxycycline. In the current study we have explored the possible mechanism by which these drugs might have worked for the positive response in the COVID-19 MESHD patients. To explore the mechanism we have used molecular docking and molecular dynamics simulation approach. Effectiveness of Ivermectin and doxycycline were evaluated against Main Protease PROTEIN ( Mpro PROTEIN), Spike (S) protein PROTEIN, Nucleocapsid (N PROTEIN), RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN, NSP12 PROTEIN), ADP Ribose Phosphatase ( NSP3 HGNC NSP3 PROTEIN), Endoribonuclease ( NSP15 PROTEIN) and methyltransferase ( NSP10 PROTEIN- NSP16 PROTEIN complex) of SARS-CoV-2 as well as human angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) receptor. Our study shows that both Ivermectin and doxycycline have significantly bind with SARS-CoV-2 proteins but Ivermectin was better binding than doxycycline. Ivermectin showed a perfect binding site to the Spike-RBD and ACE2 HGNC interacting region indicating that it might be interfering in the interaction of spike with ACE2 HGNC and preventing the viral entry in to the host cells. Ivermectin also exhibited significant binding affinity with different SARS-CoV-2 structural and non-structural proteins (NSPs) which have diverse functions in virus life cycle. Significant binding of Ivermectin with RdRp PROTEIN indicate its role in the inhibition of the viral replication and ultimately impeding the multiplication of the virus. Ivermectin also possess significant binding affinity with NSP3 HGNC NSP3 PROTEIN, NSP10 PROTEIN, NSP15 PROTEIN and NSP16 PROTEIN which helps virus in escaping from host immune system. Molecular dynamics simulation study shows that binding of the Ivermectin with Mpro PROTEIN, Spike, NSP3 HGNC NSP3 PROTEIN, NSP16 PROTEIN and ACE2 HGNC was quiet stable. Thus, our docking and simulation studies reveal that combination of Ivermectin and doxycycline might be executing the effect by inhibition of viral entry and enhance viral load clearance by targeting various viral functional proteins.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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