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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (311)

ProteinN (25)

NSP5 (13)

ORF1ab (8)

ORF8 (5)


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SARS-CoV-2 Proteins
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    Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses

    Authors: Christopher A Beaudoin; Arian Rokkum Jamasb; Ali Alsulami; Liviu Copoiu; Andries J van Tonder; Sharif Hala; Bridget P Bannerman; Sherine E Thomas; Sundeep Chaitanya Vedithi; Pedro H M Torres; Tom L Blundell

    doi:10.1101/2021.04.23.441187 Date: 2021-04-26 Source: bioRxiv

    Viruses often encode proteins that mimic host proteins in order to facilitate infection. Little work has been done to understand the potential mimicry of the SARS-CoV-2, SARS-CoV MESHD, and MERS-CoV spike proteins MESHD spike proteins PROTEIN, particularly the receptor-binding motifs, which could be important in determining tropism of the virus. Here, we use structural bioinformatics software to characterize potential mimicry of the three coronavirus spike protein PROTEIN receptor-binding motifs. We utilize sequence-independent alignment tools to compare structurally known or predicted three-dimensional protein models with the receptor-binding motifs and verify potential mimicry with protein docking simulations. Both human and non-human proteins were found to be similar to all three receptor-binding motifs. Similarity to human proteins may reveal which pathways the spike protein PROTEIN is co-opting, while analogous non-human proteins may indicate shared host interaction partners and overlapping antibody cross-reactivity. These findings can help guide experimental efforts to further understand potential interactions between human and coronavirus proteins.

    Convergent evolution of SARS-CoV-2 spike PROTEIN mutations, L452R, E484Q and P681R, in the second wave of COVID-19 MESHD in Maharashtra, India

    Authors: Sarah Cherian; Varsha Potdar; Santosh Jadhav; Pragya Yadav; Nivedita Gupta; Mousmi Das; Soumitra Das; Anurag Agarwal; Sujeet Singh; Priya Abraham; Samiran Panda; Shekhar Mande; Renu Swarup; Balram Bhargava; Rajesh Bhushan; - NIC team; - INSACOG Consortium

    doi:10.1101/2021.04.22.440932 Date: 2021-04-24 Source: bioRxiv

    As the global severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being constantly used to investigate its transmissions and evolution. In the backdrop of the global emergence of variants of concern (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein PROTEIN mutations using sequence and structural approaches was undertaken to identify possible new variants and gauge the fitness of current circulating strains. Phylogenetic analysis revealed that the predominant clade in circulation was a distinct newly identified lineage B.1.617 possessing common signature mutations D111D, G142D, L452R, E484Q, D614G and P681R, in the spike protein PROTEIN including within the receptor binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R and E484Q along with P681R in the furin cleavage site, may possibly result in increased ACE2 HGNC binding and rate of S1-S2 cleavage resulting in better transmissibility. The same two RBD mutations indicated decreased binding to selected monoclonal antibodies (mAbs) and may affect their neutralization potential. Experimental validation is warranted for accessing both ACE2 HGNC binding and the effectiveness of commonly elicited neutralizing mAbs for the strains of lineage B.1.617. The emergence of such local variants through the accumulation of convergent mutations during the COVID-19 MESHD second wave needs to be further investigated for their public health impact in the rest of the country and its possibility of becoming a VOC.

    Multiplex SARS-CoV-2 Genotyping PCR for Population-Level Variant Screening and Epidemiologic Surveillance

    Authors: Hannah Wang; Jacob Miller; Michelle Verghese; Mamdouh Sibai; Daniel Solis; Kenji O Mfuh; Becky Jiang; Naomi Iwai; Marilyn Mar; ChunHong Huang; Fumiko Yamamoto; Malaya K. Sahoo; James Zehnder; Benjamin A. Pinsky

    doi:10.1101/2021.04.20.21255480 Date: 2021-04-23 Source: medRxiv

    Emergence of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) variants with concerning phenotypic mutations is of public health interest. Genomic surveillance is an important tool for pandemic response, but many laboratories do not have the resources to support population-level sequencing. We hypothesized that a spike genotyping nucleic acid amplification test (NAAT) could facilitate high-throughput variant surveillance. We designed and analytically validated a one-step multiplex allele-specific reverse transcriptase polymerase chain reaction (RT-qPCR) to detect three non-synonymous spike protein PROTEIN mutations (L452R, E484K, N501Y). Assay specificity was validated with next-generation whole-genome sequencing. We then screened a large cohort of SARS-CoV-2 positive specimens from our San Francisco Bay Area population. Between December 1, 2020 and March 1, 2021, we screened 4,049 unique infections by genotyping RT-qPCR, with an assay failure rate of 2.8%. We detected 1,567 L452R mutations (38.7%), 34 N501Y mutations (0.84%), 22 E484K mutations (0.54%), and 3 (0.07%) E484K+N501Y mutations. The assay had near-perfect (98-100%) concordance with whole-genome sequencing in a validation subset of 229 specimens, and detected B.1.1.7, B.1.351, B.1.427, B.1.429, B.1.526, and P.2 variants, among others. The assay revealed rapid emergence of L452R in our population, with a prevalence of 24.8% in December 2020 that increased to 62.5% in March 2021. We developed and clinically implemented a genotyping RT-qPCR to conduct high-throughput SARS-CoV-2 variant screening. This approach can be adapted for emerging mutations and immediately implemented in laboratories already performing NAAT worldwide using existing equipment, personnel, and extracted nucleic acid.

    SARS-CoV-2 natural antibody response persists up to 12 months in a nationwide study from the Faroe Islands

    Authors: Maria Skaalum Petersen; Cecilie Bo Hansen; Marnar Fridheim Kristiansen; Jogvan Pall Fjallsbak; Solrun Larsen; Johanna Ljosa Hansen; Ida Jarlhelt; Laura Perez Alos; Bjarni a Steig; Debes Hammershaimb Christiansen; Lars Fodgaard Moller; Marin Strom; Gudrid Andorsdottir; Shahin Gaini; Pal Weihe; Peter Garred

    doi:10.1101/2021.04.19.21255720 Date: 2021-04-22 Source: medRxiv

    Only a few studies have assessed the long-term duration of the humoral immune response against severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). In this nationwide longitudinal study from the Faroe Islands with close to full participation of all individuals on the Islands with PCR confirmed COVID-19 MESHD during the two waves of infections in the spring and autumn 2020 (n=172 & n=233), samples were drawn at three longitudinal time points (3, 7 and 12 months and 1, 3 and 7 months after disease onset, respectively). Serum was analyzed with a direct quantitative IgG antibody binding ELISA to detect anti- SARS-CoV-2 spike PROTEIN RBD antibodies and a commercially available qualitative sandwich RBD ELISA kit measuring total antibody binding. The seropositive rate in the convalescent individuals was above 95 % at all sampling time points for both assays. There was an overall decline in IgG titers over time in both waves (p < 0.001). Pairwise comparison showed that IgG declined significantly from the first sample until approximately 7 months in both waves (p < 0.001). After that, the antibody level still declined significantly (p < 0.001), but decelerated with an altered slope remaining fairly stable from 7 months to 12 months after infection. Interestingly, the IgG titers followed a U-shaped curve with higher antibody levels among the oldest (67+) and the youngest (0-17) age groups compared to intermediate groups (p < 0.001). Our results indicate that COVID-19 MESHD convalescent individuals are likely to be protected from reinfection at least 12 months after symptom onset and maybe even longer. We believe our results can add to the understanding of natural immunity and the expected durability of SARS-CoV-2 vaccine immune responses.

    Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike PROTEIN glycoprotein

    Authors: Marco Gerdol

    doi:10.1101/2021.04.17.440288 Date: 2021-04-19 Source: bioRxiv

    Tracking the evolution of the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) through genomic surveillance programs is undoubtedly one of the key priorities in the current pandemic situation. Although the genome of SARS-CoV-2 acquires mutations at a slower rate compared with other RNA viruses, evolutionary pressures derived from the widespread circulation of SARS-CoV-2 in the human population have progressively favored the global emergence though natural selection of several variants of concern that carry multiple non-synonymous mutations in the spike glycoprotein PROTEIN. Such mutations are often placed in key sites within major antibody epitopes and may therefore confer resistance to neutralizing antibodies, leading to partial immune escape, or otherwise compensate minor infectivity deficits MESHD associated with other mutations. As previously shown by other authors, several emerging variants carry recurrent deletion regions (RDRs) that display a partial overlap with antibody epitopes located in the spike N-terminal domain. Comparatively, very little attention has been directed towards spike insertion mutations, which often go unnoticed due to the use of insertion-unaware bioinformatics analysis pipelines. This manuscript describe a single recurrent insertion region ( RIR1 HGNC) in the N-terminal domain of SARS-CoV-2 spike PROTEIN protein, characterized by the independent acquisition of 3-4 additional codons between Arg214 and Asp215 in different viral lineages. Even though RIR1 HGNC is unlikely to confer antibody escape, its progressive increase in frequency and its association with two distinct emerging lineages (A.2.5 and B.1.214.2) warrant further investigation concerning its effects on spike structure and viral infectivity.

    Inferring the stabilization effects of SARS-CoV-2 variants on the binding with ACE2 HGNC receptor

    Authors: Mattia Miotto; Lorenzo Di Rienzo; Giorgio Gosti; Leonardo Bo; Giacomo Parisi; Roberta Piacentini; Alberto Boffi; Giancarlo Ruocco; Edoardo Milanetti

    doi:10.1101/2021.04.18.440345 Date: 2021-04-19 Source: bioRxiv

    With the progression of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2 MESHD) pandemic, several variants of the virus are emerging with mutations distributed all over the viral sequence. While most of them are expected to have little to no effects at the phenotype level, some of these variants presenting specific mutations on the Spike protein PROTEIN are rapidly spreading, making urgent the need of characterizing their effects on phenotype features like contagiousness and antigenicity. With this aim, we performed extensive molecular dynamics simulations on a selected set of possible Spike variants in order to assess the stabilizing effect of particular amino acid substitutions, with a special focus on the mutations that are both characteristic of the top three most worrying variants at the moment, i.e the English, South African and Amazonian ones, and that occur at the molecular interface between SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein and its human ACE2 receptor. We characterize these variants' effect in terms of (i) residues mobility, (ii) compactness, studying the network of interactions at the interface, and (iii) variation of shape complementarity via expanding the molecular surfaces in the Zernike basis. Overall, our analyses highlighted greater stability of the three variant complexes with respect to both the wild type and two negative control systems, especially for the English and Amazonian variants. In addition, in the three variants, we investigate the effects a not-yet observed mutation in position 501 could provoke on complex stability. We found that a phenylalanine mutation behaves similarly to the English variant and may cooperate in further increasing the stability of the South African one, hinting at the need for careful surveillance for the emergence of such kind of mutations in the population. Ultimately, we show that the observables we propose describe key features for the stability of the ACE2 HGNC-spike complex and can help to monitor further possible spike variants.

    Rapid, inexpensive methods for exploring SARS CoV-2 D614G mutation

    Authors: Sirwan M.A. Al-Jaf; Sherko Subhan Niranji; Zana Hameed Mahmood

    doi:10.1101/2021.04.12.21255337 Date: 2021-04-19 Source: medRxiv

    A common mutation has occurred in the spike protein PROTEIN of severe acute respiratory syndrome coronavirus 2 MESHD (SARS CoV-2), known as D614G (A23403G). There are discrepancies in impacting of this mutation on the virus's infectivity, and the whole genome sequencings are expensive and time-consuming. This study aims to develop three fast economical assays for prompt identifications of the D614G mutation including Taqman probe-based real-time reverse transcriptase polymerase chain reaction (rRT PCR), an amplification refractory mutation system (ARMS) RT and restriction fragment length polymorphism (RFLP), in nasopharyngeal swab samples. Both rRT and ARMS data showed G614 mutant indicated by presence of HEX HGNC probe and 176bp, respectively. Additionally, the results of the RFLP data and DNA sequencings confirmed the prevalence of G614 mutant. These methods will be important, in epidemiological, reinfections and zoonotic aspects, through detecting the G614 mutant in retro-perspective samples to track its origins and future re-emergence of D614 wild type.

    Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants

    Authors: Christy L. Lavine; Shaun Rawson; Haisun Zhu; Krishna Anand; Pei Tong; Avneesh Gautam; Shen Lu; Sarah Sterling; Richard M Walsh Jr.; Jianming Lu; Wei Yang; Michael S Seaman

    doi:10.1101/2021.04.13.439709 Date: 2021-04-14 Source: bioRxiv

    Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) have become the dominant circulating strains that continue to fuel the COVID-19 pandemic MESHD despite intensive vaccination efforts throughout the world. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Mutations in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). The enhanced receptor engagement can account for the increased transmissibility and risk of mortality as the variant may begin to infect efficiently infect MESHD additional cell types expressing low levels of ACE2 HGNC. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein PROTEIN, rendering complete resistance to some potent neutralizing antibodies. These findings provide structural details on how the wide spread of SARS-CoV-2 enables rapid evolution to enhance viral fitness MESHD and immune evasion. They may guide intervention strategies to control the pandemic.

    Epitope classification and RBD binding properties of neutralizing antibodies against SARS-CoV-2 variants of concern

    Authors: Ashlesha Deshpande; Bethany D. Harris; Luis Martinez-Sobrido; James J. Kobie; Mark R Walter

    doi:10.1101/2021.04.13.439681 Date: 2021-04-13 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 MESHD (SAR-CoV-2) causes coronavirus disease 2019 MESHD ( COVID19 MESHD) that is responsible for short and long-term disease, as well as death, in susceptible hosts. The receptor binding domain (RBD) of the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN ( S) protein PROTEIN binds to cell surface angiotensin converting enzyme type-II ( ACE2 HGNC) to initiate viral attachment and ultimately viral pathogenesis. The SARS-CoV-2 S RBD MESHD is a major target of neutralizing antibodies (NAbs) that block RBD - ACE2 HGNC interactions. In this report, NAb-RBD binding epitopes in the protein databank were classified as C1, C1D, C2, C3, or C4 HGNC, using a RBD binding profile (BP), based on NAb-specific RBD buried surface area and used to predict the binding epitopes of a series of uncharacterized NAbs. Naturally occurring SARS-CoV-2 RBD sequence variation was also quantified to predict NAb binding sensitivities to the RBD-variants. NAb and ACE2 HGNC binding studies confirmed the NAb classifications and determined whether the RBD variants enhanced ACE2 HGNC binding to promote viral infectivity, and/or disrupted NAb binding to evade the host immune response. Of 9 single RBD mutants evaluated, K417T, E484K, and N501Y disrupted binding of 65% of the NAbs evaluated, consistent with the assignment of the SARS-CoV-2 P.1 Japan/Brazil strain as a variant of concern (VoC). RBD variants E484K and N501Y exhibited ACE2 HGNC binding equivalent to a Wuhan-1 reference SARS-CoV-2 RBD. While slightly less disruptive to NAb binding, L452R enhanced ACE2 HGNC binding affinity. Thus, the L452R mutant, associated with the SARS-CoV-2 California VoC MESHD (B.1.427/B.1.429-California), has evolved to enhance ACE2 HGNC binding, while simultaneously disrupting C1 and C2 NAb classes. The analysis also identified a non-overlapping antibody pair (1213H7 and 1215D1) that bound to all SARS-CoV-2 RBD variants evaluated, representing an excellent therapeutic option for treatment of SARS-CoV-2 WT MESHD and VoC strains.

    Impairment of SARS-CoV-2 spike PROTEIN glycoprotein maturation and fusion activity by the broad-spectrum anti-infective drug nitazoxanide

    Authors: Anna Riccio; Silvia Santopolo; Antonio Rossi; Sara Piacentini; Jean-Francois Rossignol; Maria Gabriella Santoro

    doi:10.1101/2021.04.12.439201 Date: 2021-04-12 Source: bioRxiv

    The emergence of the highly-pathogenic severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2), the causative agent of COVID-19 MESHD (coronavirus disease-2019), has caused an unprecedented global health crisis, as well as societal and economic disruption. The SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S), a surface-anchored trimeric class-I fusion glycoprotein essential for entry into host cells, represents a key target for developing vaccines and therapeutics capable of blocking virus invasion. The emergence of several SARS-CoV-2 spike PROTEIN variants that facilitate virus spread and may affect the efficacy of recently developed vaccines, creates great concern and highlights the importance of identifying antiviral drugs to reduce SARS-CoV-2-related morbidity and mortality. Nitazoxanide, a thiazolide originally developed as an antiprotozoal agent with recognized broad-spectrum antiviral activity in-vitro and in clinical studies, was recently shown to be effective against several coronaviruses, including SARS-CoV-2. Using biochemical and pseudovirus entry assays, we now demonstrate that nitazoxanide interferes with the SARS-CoV-2 spike PROTEIN biogenesis, hampering its maturation at an endoglycosidase H-sensitive stage, and hindering its fusion activity in human cells. Besides membrane fusion during virus entry, SARS-CoV-2 S-proteins MESHD S-proteins PROTEIN in infected cells can also trigger receptor-dependent formation of syncytia, observed in-vitro and in COVID-19 MESHD patients tissues, facilitating viral dissemination between cells and possibly promoting immune evasion. Utilizing two different quantitative cell-cell fusion assays, we show that nitazoxanide is effective in inhibiting syncytia formation mediated by different SARS-CoV-2 spike PROTEIN variants in human lung, liver and intestinal cells. The results suggest that nitazoxanide may represent a useful tool in the fight against COVID-19 MESHD infections, inhibiting SARS-CoV-2 replication and preventing spike-mediated syncytia formation.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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