Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (732)

NSP5 (34)

ProteinN (30)

ProteinS1 (28)

ComplexRdRp (23)


SARS-CoV-2 Proteins
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    Analysis of the Role of N-glycosylation in Cell-surface expression, Function and Binding Properties of SARS-CoV-2 receptor ACE2

    Authors: Alberto Brandariz-Nuñez; Raymond R Rowland

    doi:10.1101/2021.05.10.443532 Date: 2021-05-12 Source: bioRxiv

    Human angiotensin I-converting enzyme 2 HGNC ( hACE2 HGNC) is a type-I transmembrane glycoprotein that serves as the major cell entry receptor for SARS-CoV and SARS-CoV-2 MESHD. The viral spike (S) protein PROTEIN is required for attachment to ACE2 HGNC and subsequent virus-host cell membrane fusion. Previous work has demonstrated the presence of N-linked glycans in ACE2 HGNC. N-glycosylation is implicated in many biological activities, including protein folding, protein activity, and cell surface expression of biomolecules. However, the contribution of N-glycosylation to ACE2 HGNC function is poorly understood. Here, we examined the role of N-glycosylation in the activity and localization of two species with different susceptibility to SARS-CoV-2 infection MESHD, porcine ACE2 HGNC (pACE2) and hACE2 HGNC. The elimination of N-glycosylation by tunicamycin (TM) treatment or mutagenesis, showed that N-glycosylation is critical for the proper cell surface expression of ACE2 HGNC but not for its carboxiprotease activity. Furthermore, nonglycosylable ACE2 HGNC localized predominantly in the endoplasmic reticulum (ER) and not at the cell surface. Our data also revealed that binding of SARS-CoV and SARS-CoV-2 S MESHD S protein PROTEIN to porcine or human ACE2 HGNC was not affected by deglycosylation of ACE2 HGNC or S proteins PROTEIN, suggesting that N-glycosylation plays no role in the interaction between SARS coronaviruses and the ACE2 HGNC receptor. Impairment of hACE2 HGNC N-glycosylation decreased cell to cell fusion mediated by SARS-CoV S MESHD S protein PROTEIN but not SARS-CoV-2 S protein PROTEIN. Finally, we found that hACE2 HGNC N-glycosylation is required for an efficient viral entry of SARS-CoV/SARS-CoV-2 S MESHD pseudotyped viruses, which could be the result of low cell surface expression of the deglycosylated ACE2 HGNC receptor.


    Authors: Vikash Jaiswal; Danah Alquraish; Shavy Nagpal; DATTATREYA MUKHERJEE; Prakriti Singh Shrestha; Diana Sanchez Velazco; Prathima Guntipalli; Arushree Bhatnagar; Saloni Savani; Eldamhalji Halilaj Halilaj; Samir Ruxmohan

    doi:10.1101/2021.05.09.21256929 Date: 2021-05-12 Source: medRxiv

    Background: The novel Coronavirus (COVID 19) infection has affected the population with various medical issues including the underlying neurological comorbidities such as Parkinson disease MESHD. COVID 19 is found to bind with the host angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) receptors for viral entry. ACE2 HGNC receptors are normally expressed in various body surfaces as well as in the neurons and glial cells where they act as an entry port to SARS-CoV-2 infection MESHD to invade the central nervous system (CNS). ACE2 HGNC are also highly expressed in dopamine neurons which might worsen the outcome in terms of motor symptoms in PD MESHD with the treatment course. It may lead to an indirect response via immune-mediated cytokine storms and propagate through CNS leading to damage. Parkinsons disease MESHD has also been noticed due to certain post viral infections apart from COVID-19 MESHD such as, HSV, Influenza virus A, Measles virus, Cytomegalovirus and Mumps MESHD (Olsen et al, 2018). We aim to provide a thorough review on neurological outcomes and impact of COVID-19 MESHD in Parkinson disease MESHD. Methods: A systematic review was conducted to analyze the impact of COVID 19 in patients with Parkinson disease MESHD (> 21 yo). Systematic literature search was done using PubMed, Science Direct, Google Scholar and Cochrane databases. PRISMA guidelines were followed summarized in Fig. 3 for study acquisition. Results: Of the Parkinsons MESHD patients that were tested positive for SARS-CoV 2 MESHD, worsening of motor symptoms were reported along with other COVID 19 symptoms (Fig. 4 and 5). These symptoms include bradykinesia MESHD, tremors MESHD, gait disturbances MESHD, delirium MESHD and dementia MESHD and severe spasms of arms MESHD and legs. Encephalopathy MESHD was also one of the main symptoms presented in two of the studies. Increased mortality rates were identified for those who were hospitalized due to COVID-19 MESHD and PD MESHD when compared to other patients. Conclusion: Parkinsons disease MESHD may experience substantial worsening of motor and non motor symptoms during COVID 19. Due to the novelty of the virus, studies were reported from recent years and further extensive studies are needed to explore more about the disease severity and neurological outcomes when compared to other non- PD MESHD patients. Authors identify this as a limitation for this paper. Additional studies are needed to understand the role of ACE2 HGNC in increasing vulnerability to viruses and role of ACE HGNC inhibitors as treatment modality.

    Impacts on the structure-function relationship of SARS-CoV-2 spike PROTEIN by B.1.1.7 mutations

    Authors: Tzu-Jing Yang; Pei-Yu Yu; Yuan-Chih Chang; Kang-Hao Liang; Hsian-Cheng Tso; Meng-Ru Ho; Wan-Yu Chen; Hsiu-Ting Lin; Han-Chung Wu; Shang-Te Danny Hsu

    doi:10.1101/2021.05.11.443686 Date: 2021-05-12 Source: bioRxiv

    The UK variant of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) MESHD, known as B.1.1.7, harbors several point mutations and deletions on the spike (s) protein PROTEIN, which potentially alter its structural epitopes to evade host immunity while enhancing host receptor binding. Here we report the cryo-EM structures of the S protein PROTEIN of B.1.1.7 in its apo form and in the receptor ACE2 HGNC-bound form. One or two of the three receptor binding domains (RBDs) were in the open conformation but no fully closed form was observed. In the ACE-bound form, all three RBDs were engaged in receptor binding. The B.1.1.7-specific A570D mutation introduced a salt bridge switch that could modulate the opening and closing of the RBD. Furthermore, the N501Y mutation in the RBD introduced a favorable {pi}-{pi} interaction manifested in enhanced ACE2 HGNC binding affinity. The N501Y mutation abolished the neutralization activity of one of the three potent neutralizing antibodies (nAbs). Cryo-EM showed that the cocktail of other two nAbs simultaneously bound to all three RBDs. Furthermore, the nAb cocktail synergistically neutralized different SARS-CoV-2 pseudovirus strains, including the B.1.1.7.

    Energy Landscape of the SARS-CoV-2 Reveals Extensive Conformational Heterogeneity

    Authors: Ghoncheh Mashayekhi; John Vant; Abhishek Singharoy; Abbas Ourmazd

    doi:10.1101/2021.05.11.443708 Date: 2021-05-12 Source: bioRxiv

    Cryo-electron microscopy (cryo-EM) has produced a number of structural models of the SARS-CoV-2 spike PROTEIN, already prompting biomedical outcomes. However, these reported models and their associated electrostatic potential maps represent an unknown admixture of conformations stemming from the underlying energy landscape of the spike protein PROTEIN. As for any protein, some of the spike's PROTEIN conformational motions are expected to be biophysically relevant, but cannot be interpreted only by static models. Using experimental cryo-EM images, we present the energy landscape of the spike protein PROTEIN conformations, and identify molecular rearrangements along the most-likely conformational path in the vicinity of the open (so called 1RBD-up) state. The resulting global and local atomic refinements reveal larger movements than those expected by comparing the reported 1RBD-up and 1RBD-down cryo-EM models. Here we report greater degrees of "openness MESHD" in global conformations of the 1RBD-up state, not revealed in the single-model interpretations of the density maps, together with conformations that overlap with the reported models. We discover how the glycan shield contributes to the stability of these conformations along the minimum free-energy pathway. A local analysis of seven key binding pockets reveals that six out them, including those for engaging ACE2 HGNC, therapeutic mini-proteins, linoleic acid, two different kinds of antibodies, and protein-glycan interaction sites, switch conformations between their known apo- and holo-conformations, even when the global spike conformation is 1RBD-up. This is reminiscent of a conformational pre-equilibrium. We found only one binding pocket, namely antibody AB-C135 to remain closed along the entire minimum free energy path, suggesting an induced fit mechanism for this enzyme.

    Dynamic Interactions of Fully Glycosylated SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN Protein with Various Antibodies

    Authors: Yiwei Cao; Yeol Kyo Choi; Martin Frank; Hyeonuk Woo; Sang-Jun Park; Min Sun Yeom; Chaok Seok; Wonpil Im

    doi:10.1101/2021.05.10.443519 Date: 2021-05-11 Source: bioRxiv

    The spread of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) presents a public health crisis, and the vaccines that can induce highly potent neutralizing antibodies are essential for ending the pandemic. The spike (S) protein PROTEIN on the viral envelope mediates human angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) binding and thus is the target of a variety of neutralizing antibodies. In this work, we built various S trimer-antibody complex structures on the basis of the fully glycosylated S protein PROTEIN models described in our previous work, and performed all-atom molecular dynamics simulations to get insight into the structural dynamics and interactions between S protein PROTEIN and antibodies. Investigation of the residues critical for S-antibody binding allows us to predict the potential influence of mutations in SARS-CoV-2 variants. Comparison of the glycan conformations between S-only and S-antibody systems reveals the roles of glycans in S-antibody binding. In addition, we explored the antibody binding modes, and the influences of antibody on the motion of S protein PROTEIN receptor binding domains. Overall, our analyses provide a better understanding of S-antibody interactions, and the simulation-based S-antibody interaction maps could be used to predict the influences of S mutation on S-antibody interactions, which will be useful for the development of vaccine and antibody-based therapy.

    Antibody Responses After a Single Dose of ChAdOx1 nCoV-19 Vaccine in Healthcare Workers Previously Infected with SARS-CoV-2

    Authors: Sebastian Havervall; Ulrika Marking; Nina Greilert-Norin; Henry Ng; Ann-Christin Salomonsson; Cecilia Hellstrom; Elisa Pin; Kim Blom; Sara Mangsbo; Mia Phillipson; Jonas Klingstrom; Mikael Aberg; Sophia Hober; Peter Nilsson; Charlotte Thalin

    doi:10.1101/2021.05.08.21256866 Date: 2021-05-11 Source: medRxiv

    Background Recent reports demonstrate robust serological responses to a single dose of messenger RNA (mRNA) vaccines in individuals previously infected with SARS-CoV-2. Data on immune responses following a single-dose adenovirus-vectored vaccine expressing the SARS-CoV-2 spike PROTEIN protein (ChAdOx1 nCoV-19) in individuals with previous SARS-CoV-2 infection MESHD are however limited, and current guidelines recommend a two-dose regime regardless of preexisting immunity. Methods We compared spike-specific IgG and pseudo-neutralizing spike- ACE2 HGNC blocking antibodies against SARS-CoV-2 wild type and variants B.1.1.7, B.1.351, and P1 following two doses of the mRNA vaccine BNT162b2 and a single dose of the adenovector vaccine ChAdOx1 nCoV-19 in 232 healthcare workers with and without previous COVID-19 MESHD. Findings The post-vaccine levels of spike-specific IgG and neutralizing antibodies against the SARS-CoV-2 wild type and all three variants of concern were similar or higher in participants receiving a single dose of ChAdOx1 nCoV-19 vaccine post SARS-CoV-2 infection MESHD (both < 11 months post infection (n=37) and [≥] 11 months infection (n=46)) compared to participants who received two doses of BNT162b2 vaccine (n=149). Interpretation Our data support that a single dose ChAdOx1 nCoV-19 vaccine serves as an effective immune booster after priming with natural SARS-CoV-2 infection MESHD up to at least 11 months post infection.

    Structure and mechanism of SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD N679-V687 deletion variant elucidate cell-type specific evolution of viral fitness

    Authors: Kapil Gupta; Christine Toelzer; Maia Kavanagh Williamson; Deborah Shoemark; A. Sofia F. Oliveira; David A Matthews; Abdulaziz Almuqrin; Oskar Staufer; Sathish K.N. Yadav; Ufuk Borucu; Frederic Garzoni; Daniel Fitzgerald; Joachim Spatz; Adrian J Mulholland; Andrew D. Davidson; Christiane Schaffitzel; Imre Berger

    doi:10.1101/2021.05.11.443384 Date: 2021-05-11 Source: bioRxiv

    As the global burden of SARS-CoV-2 infections escalates MESHD, so does the evolution of viral variants which is of particular concern due to their potential for increased transmissibility and pathology. In addition to this entrenched variant diversity in circulation, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriS{Delta} variant, originally identified as a viral subpopulation by passaging SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike glycoprotein PROTEIN an eight amino-acid deletion encompassing the furin recognition motif and S1/S2 cleavage site. Here, we analyzed the structure, function and molecular dynamics of this variant spike, providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 HGNC receptor binding and infectivity, allowing the virus to probe diverse trajectories in distinct cell types to evolve viral fitness MESHD. TeaserSARS-CoV-2 can exploit different cell types to diversify and evolve virus variants distinct in infectivity and structure.

    SARS-CoV-2 receptor ACE2 HGNC identifies immuno-hot tumors in breast cancer MESHD


    doi:10.1101/2021.05.10.443377 Date: 2021-05-10 Source: bioRxiv

    Angiotensin-converting enzyme 2 ( ACE2 HGNC) is known as a host cell receptor for Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2), which is identified to be dysregulated MESHD in multiple tumors MESHD. Although the characterization of abnormal ACE2 HGNC expression in malignancies MESHD has been preliminarily explored, in-depth analysis of ACE2 HGNC in breast cancer MESHD ( BRCA HGNC BRCA MESHD) has not been elucidated. A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 HGNC based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). Next, correlations between ACE2 HGNC expression immunological characteristics in the BRCA tumor MESHD BRCA tumor HGNC microenvironment (TME) were evaluated. Also, the role of ACE2 HGNC in predicting the clinical features and the response to therapeutic options in BRCA MESHD BRCA HGNC was estimated. These findings were subsequently validated in another public transcriptomic cohort as well as a recruited cohort. ACE2 HGNC was lowly expressed in most cancers MESHD compared with adjacent tissues. ACE2 HGNC was positively correlated with immunomodulators, tumor MESHD-infiltrating immune cells (TIICs), cancer MESHD immunity cycles, immune checkpoints, and tumor MESHD mutation burden (TMB). Besides, high ACE2 HGNC levels indicated the triple-negative breast cancer MESHD ( TNBC MESHD) subtype of BRCA HGNC BRCA MESHD, lower response to endocrine therapy and higher response to chemotherapy, anti- ERBB HGNC therapy, antiangiogenic therapy and immunotherapy. To sum up, ACE2 HGNC correlates with an inflamed TME and identifies immuno-hot tumors MESHD, which may be used as an auxiliary biomarker for the identification of immunological characteristics in BRCA MESHD BRCA HGNC.

    SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity MESHD


    doi:10.1101/2021.05.09.443331 Date: 2021-05-10 Source: bioRxiv

    The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of prefusion Spike (S), S1 and RBD HGNC. These immunogens induced robust S-binding, ACE2-inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2 in mice. A Spike-ferritin nanoparticle (SpFN) vaccine elicited neutralizing titers more than 20-fold higher than convalescent donor serum, following a single immunization, while RBD-Ferritin nanoparticle ( RFN MESHD) immunogens elicited similar responses after two immunizations. Passive transfer of IgG purified from SpFN- or RFN-immunized mice protected K18- hACE2 HGNC transgenic mice from a lethal SARS-CoV-2 virus challenge. Furthermore, SpFN- and RFN-immunization elicited ACE2 blocking activity and neutralizing ID50 antibody titers >2,000 against SARS-CoV-1, along with high magnitude neutralizing titers against major VoC. These results provide design strategies for pan-coronavirus vaccine development.

    The K18- hACE2 HGNC Transgenic Mouse Model Recapitulates Non-Severe and Severe COVID-19 MESHD in Response to Infectious Dose of SARS-CoV-2 Virus


    doi:10.1101/2021.05.08.443244 Date: 2021-05-09 Source: bioRxiv

    A comprehensive analysis and characterization of a SARS-CoV-2 infection MESHD model that mimics non-severe and severe COVID-19 MESHD in humans is warranted for understating the virus and developing preventive and therapeutic agents. Here, we characterized the K18- hACE2 HGNC mouse model expressing human (h) ACE2 HGNC in mice, controlled by the human keratin 18 HGNC ( K18 HGNC) promoter, in epithelia, including airway epithelial cells where SARS-CoV-2 infections MESHD typically start. We found that intranasal inoculation with higher viral doses (2x103 and 2x104 PFU) of SARS-CoV-2 caused lethality of all mice and severe damage of various organs, including lungs, liver, and kidney MESHD, while lower doses (2x101 and 2x102 PFU) led to less severe tissue damage and some mice recovered from the infection. In this humanized hACE2 HGNC mouse model, SARS-CoV-2 infection MESHD damaged multiple tissues, with a dose-dependent effect in most tissues. Similar damage was observed in biopsy samples from COVID-19 MESHD patients. Finally, the mice that recovered after infection with a low dose of virus also survived rechallenge with a high dose of virus. Compared to other existing models, the K18- hACE2 HGNC model seems to be the most sensitive COVID-19 MESHD model reported to date. Our work expands the information available about this model to include analysis of multiple infectious doses and various tissues with comparison to human biopsy samples from COVID-19 MESHD patients. In conclusion, the K18- hACE2 HGNC mouse model recapitulates both severe and non-severe COVID-19 MESHD in humans and can provide insight into disease progression and the efficacy of therapeutics for preventing or treating COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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