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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (227)

ProteinN (83)

NSP5 (52)

ComplexRdRp (21)

NSP3 (16)


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SARS-CoV-2 Proteins
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    Prediction of Ciclesonide Binding Site on Middle-East Respiratory Syndrome MESHD Coronavirus Nsp15 Multimer by Molecular Dynamics Simulations

    Authors: Shun Sakuraba; Hidetoshi Kono

    doi:10.26434/chemrxiv.13602731.v1 Date: 2021-01-19 Source: ChemRxiv

    Ciclesonide, a corticosteroid, was known to inhibit the growth of Middle-east respiratory syndrome MESHD ( MERS MESHD) coronavirus. However, its molecular mechanism was unknown. We tried to uncover the molecular mechanism from the molecular dynamics simulation.SARS_CoV_2_nsp15.pdf: The preprint document.nsp15-mers-supp.zip: Supplemental data including binding poses and parameter files for the simulation.

    mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

    Authors: Zijun Wang; Fabian Schmidt; Yiska Weisblum; Frauke Muecksch; Christopher O Barnes; Shlomo Finkin; Dennis Schaefer-Babajew; Melissa Cipolla; Christian Gaebler; Jenna A Lieberman; Zhi Yang; Morgan E Abernathy; Kathryn E Huey-Tubman; Arlene Hurley; Martina Turroja; Kamille A West; Kristie Gordon; Katrina G Millard; Victor Ramos; Justin Da Silva; Jianliang Xu; Robert A Colbert; Roshni Patel; Juan P Dizon; Irina Shimeliovich; Anna Gazumyan; Marina Caskey; Pamela J Bjorkman; Rafael Casellas; Theodora Hatziioannou; Paul D Bieniasz; Michel C Nussenzweig

    doi:10.1101/2021.01.15.426911 Date: 2021-01-19 Source: bioRxiv

    To date severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) has infected nearly 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease-2019 ( COVID-19 MESHD) including two novel mRNA-based vaccines. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti- SARS-CoV-2 spike PROTEIN protein (S PROTEIN), receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes epitopes MESHD in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus MESHD (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

    Rapid protection from COVID-19 MESHD in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine

    Authors: Wakako Furuyama; Kyle Shifflett; Amanda N Pinksi; Amanda J Griffin; Friederike Feldmann; Atsushi Okumura; Tylisha Gourdine; Allen Jankeel; Jamie Lovaglio; Patrick W Hanley; Tina Thomas; Chad S Clancy; Ilhem Messaoudi; Andrea Marzi; Martina Turroja; Kamille A West; Kristie Gordon; Katrina G Millard; Victor Ramos; Justin Da Silva; Jianliang Xu; Robert A Colbert; Roshni Patel; Juan P Dizon; Irina Shimeliovich; Anna Gazumyan; Marina Caskey; Pamela J Bjorkman; Rafael Casellas; Theodora Hatziioannou; Paul D Bieniasz; Michel C Nussenzweig

    doi:10.1101/2021.01.19.426885 Date: 2021-01-19 Source: bioRxiv

    The ongoing pandemic of Coronavirus disease 2019 MESHD ( COVID-19 MESHD) continues to exert a significant burden on health care systems worldwide. With limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). Recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against SARS-CoV-2. Here, we generated a single dose, fast-acting vesicular stomatitis MESHD virus-based vaccine derived from the licensed Ebola virus (EBOV) vaccine rVSV-ZEBOV, expressing the SARS-CoV-2 spike PROTEIN protein and the EBOV glycoprotein (VSV-SARS2-EBOV). Rhesus macaques vaccinated intramuscularly (IM) with a single dose of VSV-SARS2-EBOV were protected within 10 days and did not show signs of COVID-19 MESHD pneumonia MESHD. In contrast, IN vaccination MESHD resulted in limited immunogenicity and enhanced COVID-19 MESHD pneumonia MESHD compared to control animals. While IM and IN vaccination both induced neutralizing antibody titers MESHD, only IM vaccination resulted in a significant cellular immune response. RNA sequencing data bolstered these results by revealing robust activation of the innate and adaptive immune transcriptional signatures in the lungs of IM-vaccinated animals only. Overall, the data demonstrates that VSV-SARS2-EBOV is a potent single-dose COVID-19 MESHD vaccine candidate that offers rapid protection based on the protective efficacy observed in our study.

    An all-solid-state heterojunction oxide transistor for the rapid detection of biomolecules and SARS-CoV-2 spike PROTEIN S1 protein PROTEIN

    Authors: Yen-Hung Lin; Yang Han; Abhinav Sharma; Wejdan S. AlGhamdi; Chien-Hao Liu; Tzu-Hsuan Chang; Xi-Wen Xiao; Akmaral Seitkhan; Alexander D. Mottram; Pichaya Pattanasattayavong; Hendrik Faber; Martin Heeney; Thomas D. Anthopoulos; Paola de Sessions; Andres Merits; Lin-Fa Wang; Roland G Huber; Catherine M. Green; Teresa Lambe; Peijun Zhang; Sarah C Gilbert; Max Crispin; Roshni Patel; Juan P Dizon; Irina Shimeliovich; Anna Gazumyan; Marina Caskey; Pamela J Bjorkman; Rafael Casellas; Theodora Hatziioannou; Paul D Bieniasz; Michel C Nussenzweig

    doi:10.1101/2021.01.19.427256 Date: 2021-01-19 Source: bioRxiv

    Solid-state transistor sensors that can detect biomolecules in real time are highly attractive for emerging bioanalytical applications. However, combining cost-effective manufacturing with high sensitivity, specificity and fast sensing response, remains challenging. Here we develop low-temperature solution-processed In2O3/ZnO heterojunction transistors featuring a geometrically engineered tri-channel architecture for rapid real-time detection of different biomolecules. The sensor combines a high electron mobility channel, attributed to the quasi-two-dimensional electron gas (q2DEG) at the buried In2O3/ZnO heterointerface, in close proximity to a sensing surface featuring tethered analyte receptors. The unusual tri-channel design enables strong coupling between the buried q2DEG and the minute electronic perturbations occurring during receptor-analyte interactions allowing for robust, real-time detection of biomolecules down to attomolar (aM) concentrations. By functionalizing the tri-channel surface with SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2 MESHD) antibody receptors, we demonstrate real-time detection of the SARS-CoV-2 spike PROTEIN S1 protein PROTEIN down to attomolar concentrations in under two minutes.

    A trans-complementation system for SARS-CoV-2

    Authors: Xianwen Zhang; Yang Liu; Jianying Liu; Adam L Bailey; Kenneth S Plante; Jessica A Plante; Jing Zou; Hongjie Xia; Nathen E Bopp; Patricia V Aguilar; Ping Ren; Vineet D Menachery; Michael S Diamond; Scott C Weaver; Xuping Xie; Pei-Yong Shi; Udeni BR Balasuriya; Adolfo Garcia-Sastre; Juergen A Richt; Marit J van Gils; Laura E McCoy; Max Crispin; Roshni Patel; Juan P Dizon; Irina Shimeliovich; Anna Gazumyan; Marina Caskey; Pamela J Bjorkman; Rafael Casellas; Theodora Hatziioannou; Paul D Bieniasz; Michel C Nussenzweig

    doi:10.1101/2021.01.16.426970 Date: 2021-01-19 Source: bioRxiv

    The biosafety level-3 (BSL-3) requirement to culture severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is a bottleneck for research and countermeasure development. Here we report a trans-complementation system that produces single-round infectious SARS-CoV-2 that recapitulates authentic viral replication. We demonstrate that the single-round infectious SARS-CoV-2 can be used at BSL-2 laboratories for high-throughput neutralization and antiviral testing. The trans-complementation system consists of two components: a genomic viral RNA containing a deletion of ORF3 HGNC and envelope gene, and a producer cell line expressing the two deleted genes. Trans-complementation of the two components generates virions that can infect naive cells for only one round, but does not produce wild-type SARS-CoV-2. Hamsters and K18- hACE2 HGNC transgenic mice inoculated with the complementation-derived virions exhibited no detectable disease, even after intracranial inoculation with the highest possible dose. The results suggest that the trans-complementation platform can be safely used at BSL-2 laboratories for research and countermeasure development.

    Sterically-Confined Rearrangements of SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN Protein Control Cell Invasion

    Authors: Esteban Dodero Rojas; Jose Nelson Onuchic; Paul Whitford; Merissa Chen; Gokul N Ramadoss; Xiaoyan Guo; Alice Mac Kain; Quang Dinh Tran; Shion A Lim; Irene Lui; James Nunez; Sarah J Rockwood; Na Liu; Jared Carlson-Stevermer; Jennifer Oki; Travis Maures; Kevin Holden; Jonathan S Weissman; James A Wells; Bruce Conklin; Marco Vignuzzi; Martin Kampmann; Roshni Patel; Juan P Dizon; Irina Shimeliovich; Anna Gazumyan; Marina Caskey; Pamela J Bjorkman; Rafael Casellas; Theodora Hatziioannou; Paul D Bieniasz; Michel C Nussenzweig

    doi:10.1101/2021.01.18.427189 Date: 2021-01-19 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is highly contagious, and transmission involves a series of processes that may be targeted by vaccines and therapeutics. During transmission, host cell invasion is controlled by a large-scale conformational change of the Spike protein PROTEIN. This conformational rearrangement leads to membrane fusion, which creates transmembrane pores through which the viral genome is passed to the host. During Spike-protein PROTEIN-mediated fusion, the fusion peptides must be released from the core of the protein and associate with the host membrane. Interestingly, the Spike protein PROTEIN possesses many post-translational modifications, in the form of branched glycans that flank the surface of the assembly. Despite the large number of glycosylation sites, until now, the specific role of glycans during cell invasion has been unclear. Here, we propose that glycosylation is needed to provide sufficient time for the fusion peptides to reach the host membrane, otherwise the viral particle would fail to enter the host. To understand this process, an all-atom model with simplified energetics was used to perform thousands of simulations in which the protein transitions between the prefusion and postfusion conformations. These simulations indicate that the steric composition of the glycans induces a pause during the Spike protein PROTEIN conformational change. We additionally show that this glycan-induced delay provides a critical opportunity for the fusion peptides to capture the host cell. This previously-unrecognized role of glycans reveals how the glycosylation state can regulate infectivity of this pervasive pathogen.

    SARS-CoV-2 RECoVERY: a multi-platform open-source bioinformatic pipeline for the automatic construction and analysis of SARS-CoV-2 genomes from NGS sequencing data

    Authors: Luca De Sabato; Gabriele Vaccari; Arnold Knijn; Giovanni Ianiro; Ilaria Di Bartolo; Stefano Morabito

    doi:10.1101/2021.01.16.425365 Date: 2021-01-18 Source: bioRxiv

    Background: Since its first appearance in December 2019, the novel Severe Acute Respiratory Syndrome Coronavirus type 2 MESHD (SARSCoV2), spread worldwide causing an increasing number of cases and deaths MESHD (35,537,491 and 1,042,798, respectively at the time of writing, https:// covid19 MESHD.who.int). Similarly, the number of complete viral genome sequences produced by Next Generation Sequencing (NGS), increased exponentially. NGS enables a rapid accumulation of a large number of sequences. However, bioinformatics analyses are critical and require combined approaches for data analysis, which can be challenging for non bioinformaticians. Results: A user friendly and sequencing platform-independent bioinformatics pipeline, named SARSCoV2 RECoVERY (REconstruction of CoronaVirus gEnomes & Rapid analYsis) has been developed to build SARSCoV2 complete genomes from raw sequencing reads and to investigate variants. The genomes built by SARSCoV2 RECoVERY were compared with those obtained using other software available and revealed comparable or better performances of SARSCoV2 RECoVERY. Depending on the number of reads, the complete genome reconstruction and variants analysis can be achieved in less than one hour. The pipeline was implemented in the multi usage open source Galaxy platform allowing an easy access to the software and providing computational and storage resources to the community. Conclusions: SARSCoV2 RECoVERY is a piece of software destined to the scientific community working on SARSCoV2 phylogeny and molecular characterisation, providing a performant tool for the complete reconstruction and variants analysis of the viral genome. Additionally, the simple software interface and the ability to use it through a Galaxy instance without the need to implement computing and storage infrastructures, make SARSCoV2 RECoVERY a resource also for virologists with little or no bioinformatics skills. Availability and implementation: The pipeline SARSCoV2 RECoVERY (REconstruction of COronaVirus gEnomes & Rapid analYsis) is implemented in the Galaxy instance ARIES (https://aries.iss.it).

    Tropism of SARS-CoV-2 MESHD for Developing Human Cortical Astrocytes

    Authors: Madeline G Andrews; Tanzila Mukhtar; Ugomma C Eze; Camille R Simoneau; Yonatan Perez; Mohammed A Mostajo-Radji; Shaohui Wang; Dmitry Velmeshev; Jahan Salma; G. Renuka Kumar; Alex A Pollen; Elizabeth E Crouch; Melanie Ott; Arnold R Kriegstein

    doi:10.1101/2021.01.17.427024 Date: 2021-01-18 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) readily infects MESHD a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those infected. Neurological symptoms MESHD, which range in severity, accompany a significant proportion of COVID-19 MESHD cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized primary human cortical tissue and stem cell-derived cortical organoids. We find significant and predominant infection in cortical astrocytes in both primary and organoid cultures, with minimal infection of other cortical populations. Infected astrocytes had a corresponding increase in reactivity characteristics, growth factor signaling, and cellular stress. Although human cortical cells, including astrocytes, have minimal ACE2 HGNC expression, we find high levels of alternative coronavirus receptors in infected astrocytes, including DPP4 HGNC and CD147 HGNC. Inhibition of DPP4 HGNC reduced infection and decreased expression of the cell stress marker, ARCN1 HGNC. We find tropism of SARS-CoV-2 MESHD for human astrocytes mediated by DPP4 HGNC, resulting in reactive gliosis-type injury MESHD.

    N-(4-Hydroxyphenyl)retinamide suppresses SARS-CoV-2 spike PROTEIN protein-mediated cell-cell fusion and viral infection in vitro  MESHD

    Authors: Yasuhiro Hayashi; Kiyoto Tsuchiya; Mizuki Yamamoto; Yoko Nemoto-Sasaki; Kazunari Tanigawa; Kotaro Hama; Takashi Tanikawa; Jin Gohda; Kenji Maeda; Jun-ichiro Inoue; Atsushi Yamashita

    doi:10.21203/rs.3.rs-148750/v1 Date: 2021-01-16 Source: ResearchSquare

    The coronavirus disease ( COVID-19 MESHD) pandemic, caused by severe acute r espiratory syndrome coronavirus 2 MESHD(SARS-CoV-2), persists worldwide with limited therapeutic options. Since membrane fusion between SARS-CoV-2 and host cells is essential for the early step of the i nfection, MESHD the membrane compositions, including sphingolipids, in host cells are considered to affect the v iral infection. MESHD However, the role of sphingolipids in the life cycle of S ARS-CoV-2 MESHDremains unclear. Here, we assessed several inhibitors of sphingolipid metabolism enzymes against SARS-CoV-2 spike PROTEIN protein-mediated cell-cell fusion and v iral infection MESHDin vitro. Among the compounds tested, only N-(4-hydroxyphenyl)retinamide (4-H PR, HGNC also known as fenretinide), an inhibitor of dihydroceramide Δ4-desaturase 1 (D ES1) HGNC and well known for having antitumour activity, suppressed cell-cell fusion (50% effective concentration [EC50] = 4.1 mM) and v iral infection MESHD([EC50] = 4.4 mM), wherein the EC50 values are below its plasma concentration in previous clinical trials on t umours. MESHD D ES1 HGNCcatalyses the introduction of a double bond in dihydroceramide, and the inhibition efficiencies observed were consistent with an increased ratio of saturated sphinganine-based lipids to total sphingolipids and the decreased cellular membrane fluidity. These findings, together with the accumulated clinical data regarding the safety of 4-H PR, HGNC make it a likely candidate drug to treat COVID-19 MESHD.

    WHO vaccination protocol can be improved to save more lives MESHD

    Authors: Marcelo Moret; Tarcisio Rocha Filho; José Mendes; Thiago Murari; Aloísio Nascimento Filho; Antônio Cordeiro; Walter Ramalho; Fulvio Scorza; Antonio-Carlos Almeida

    doi:10.21203/rs.3.rs-148826/v1 Date: 2021-01-16 Source: ResearchSquare

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic, a virus infection MESHD caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) virus, has impacted all countries of the world, and the main 2021’s challenge is clearly vaccinating the greater number of persons, in the shortest time span, for a maximal reduction in the number of deaths MESHD and in the significant economic impacts. Large-scale vaccination aimed to achieve herd immunity poses many logistic and social difficulties [1], with different vaccine candidates and designs [2,3], and vaccination priorities will determine the evolution of the current COVID-19 pandemic MESHD. In this paper we explicitly propose an alternative vaccination protocol that can be more effective than those already being deployed, as the ones in the European Union [4] and in the United States [5]. We report strong evidence based on an epidemiological model for the importance of contact hubs (or superspreaders), having a much larger average number of contacts than in the rest of the population [6-11], on the effectiveness of the vaccination strategy. We show that carefully choosing who will be in the first group to be vaccinated can significantly impact on both health services demand and total death toll, by increasing the overall numbers of lives saved and of hospitalizations. We argue that the approach here considered, which does not coincide with current proposals, and given the current conditions with a lack of basic resources for proper vaccination in several countries, and with a significant reduction in mobility and social isolation restrictions, should be considered by all authorities participating in the design of COVID-19 MESHD vaccination with the intent of maximising the number of human lives saved.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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