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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (1608)

ProteinN (451)

NSP5 (379)

ComplexRdRp (215)

ProteinE (121)


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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.

    SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 MESHD donor plasma

    Authors: Constantinos Kurt Wibmer; Frances Ayres; Tandile Hermanus; Mashudu Madzivhandila; Prudence Kgagudi; Bronwen E Lambson; Marion Vermeulen; Karin van den Berg; Theresa Rossouw; Michael Boswell; Veronica Ueckermann; Susan Meiring; Anne von Gottberg; Cheryl Cohen; Lynn Morris; Jinal N Bhiman; Penny L Moore

    doi:10.1101/2021.01.18.427166 Date: 2021-01-19 Source: bioRxiv

    SARS-CoV-2 501Y.V2, a novel lineage of the coronavirus causing COVID-19 MESHD, contains multiple mutations within two immunodominant domains of the spike protein PROTEIN. Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 MESHD convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines.

    Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera

    Authors: Alexander Muik; Ann-Kathrin Wallisch; Bianca Saenger; Kena A Swanson; Julia Muehl; Wei Chen; Hui Cai; Ritu Sarkar; Oezlem Tuereci; Philip R Dormitzer; Ugur Sahin; Susan Meiring; Anne von Gottberg; Cheryl Cohen; Lynn Morris; Jinal N Bhiman; Penny L Moore

    doi:10.1101/2021.01.18.426984 Date: 2021-01-19 Source: bioRxiv

    Recently, a new SARS-CoV-2 lineage called B.1.1.7 has emerged in the United Kingdom that was reported to spread more efficiently than other strains. This variant has an unusually large number of mutations with 10 amino acid changes in the spike protein PROTEIN, raising concerns that its recognition by neutralizing antibodies may be affected. Here, we investigated SARS-CoV-2-S pseudoviruses bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein PROTEIN with sera of 16 participants in a previously reported trial with the mRNA-based COVID-19 MESHD vaccine BNT162b2. The immune sera had equivalent neutralizing titers to both variants. These data, together with the combined immunity involving humoral and cellular effectors induced by this vaccine, make it unlikely that the B.1.1.7 lineage will escape BNT162b2-mediated protection.

    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.

    Native-like SARS-CoV-2 spike PROTEIN glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine

    Authors: Yasunori Watanabe; Luiza Mendonça; Elizabeth R. Allen; Andrew Howe; Mercede Lee; Joel D Allen; Himanshi Chawla; David Pulido; Francesca Donnellan; Hannah Davies; Marta Ulaszewska; Sandra Belij-Rammerstorfer; Susan Morris; Wanwisa Dejnirattisai; Juthathip Mongkolsapaya; Piyada Supasa; Gavin R. Screaton; 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:10.1101/2021.01.15.426463 Date: 2021-01-19 Source: bioRxiv

    Vaccine development against the SARS-CoV-2 virus focuses on the principal target of the neutralizing immune response, the spike ( S) glycoprotein PROTEIN. Adenovirus-vectored vaccines offer an effective platform for the delivery of viral antigen, but it is important for the generation of neutralizing antibodies that they produce appropriately processed and assembled viral antigen that mimics that observed on the SARS-CoV-2 virus. Here, we describe the structure, conformation and glycosylation of the S protein PROTEIN derived from the adenovirus-vectored ChAdOx1 nCoV-19/AZD1222 vaccine. We demonstrate native-like post-translational processing and assembly, and reveal the expression of S proteins PROTEIN on the surface of cells adopting the trimeric prefusion conformation. The data presented here confirms the use of ChAdOx1 adenovirus vectors as a leading platform technology for SARS-CoV-2 vaccines.

    Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions

    Authors: Yue Wan; Siwy Ling Yang; Louis DeFalco; Danielle E Anderson; Yu Zhang; Ashley J Aw; Su Ying Lim; Xin Ni Lim; Kiat Yee Tan; Tong Zhang; Tanu Chawla; Yan Su; Alexander Lezhava; 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:10.1101/2021.01.17.427000 Date: 2021-01-19 Source: bioRxiv

    SARS-CoV-2 has emerged as a major threat to global public health, resulting in global societal and economic disruptions. Here, we investigate the intramolecular and intermolecular RNA interactions of wildtype (WT) and a mutant ({Delta}382) SARS-CoV-2 virus in cells using high throughput structure probing on Illumina and Nanopore platforms. We identified twelve potentially functional structural elements within the SARS-CoV-2 genome, observed that identical sequences can fold into divergent structures on different subgenomic RNAs, and that WT and {Delta}382 virus genomes can fold differently. Proximity ligation sequencing experiments identified hundreds of intramolecular and intermolecular pair-wise interactions within the virus genome and between virus and host RNAs. SARS-CoV-2 binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2'-O-methylated. 2'-O-methylation sites in the virus genome are enriched in the untranslated regions and are associated with increased pair-wise interactions. SARS-CoV-2 infection MESHD results in a global decrease of 2'-O-methylation sites on host mRNAs, suggesting that binding to snoRNAs could be a pro-viral mechanism to sequester methylation machinery from host RNAs towards the virus genome. Collectively, these studies deepen our understanding of the molecular basis of SARS-CoV-2 pathogenicity, cellular factors important during infection and provide a platform for targeted therapy.

    Interferon-regulated genetic programs and JAK/STAT pathway activate the intronic promoter of the short ACE2 HGNC isoform in renal proximal tubules

    Authors: Yue Wan; Siwy Ling Yang; Louis DeFalco; Danielle E Anderson; Yu Zhang; Ashley J Aw; Su Ying Lim; Xin Ni Lim; Kiat Yee Tan; Tong Zhang; Tanu Chawla; Yan Su; Alexander Lezhava; 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:10.1101/2021.01.15.426908 Date: 2021-01-19 Source: bioRxiv

    Summary: Recently, a short, interferon-inducible isoform of Angiotensin-Converting Enzyme 2 ( ACE2 HGNC), dACE2 was identified. ACE2 HGNC is a SARS-Cov-2 receptor and changes in its renal expression have been linked to several human nephropathies MESHD. These changes were never analyzed in context of dACE2, as its expression was not investigated in the kidney. We used Human Primary Proximal Tubule (HPPT) cells to show genome-wide gene expression patterns after cytokine stimulation, with emphasis on the ACE2 HGNC/dACE2 locus. Putative regulatory elements controlling dACE2 expression were identified using ChIP-seq and RNA-seq. qRT-PCR differentiating between ACE2 HGNC and dACE2 revealed 300- and 600-fold upregulation of dACE2 by IFN and IFN{beta}, respectively, while full length ACE2 HGNC expression was almost unchanged. JAK inhibitor ruxolitinib ablated STAT1 HGNC and dACE2 expression after interferon treatment. Finally, with RNA-seq, we identified a set of genes, largely immune-related, induced by cytokine treatment. These gene expression profiles provide new insights into cytokine response of proximal tubule cells.

    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.

    The impact of Spike mutations on SARS-CoV-2 neutralization

    Authors: Chloe Rees-Spear; Luke Muir; Sarah A Griffith; Judith Heaney; Yoann Aldon; Jonne Snitselaar; Peter Thomas; Carl Graham; Jeffrey Seow; Nayung Lee; Annachiara Rosa; Chloe Roustan; Catherine F Houlihan; Rogier W Sanders; Ravindra K Gupta; Peter Cherepanov; Hans Stauss; Eleni Nastouli; Katie J Doores; 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:10.1101/2021.01.15.426849 Date: 2021-01-19 Source: bioRxiv

    Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike PROTEIN. Antibodies from SARS-CoV-2 infection MESHD neutralize the virus by focused targeting of Spike and there is limited serum cross-neutralization of the closely-related SARS-CoV. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, 501Y.V2 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus MESHD or the current vaccines will remain effective against virus variants. In this study we evaluate neutralization of a series of mutated Spike pseudotypes including a B.1.1.7 Spike pseudotype. The analyses of a panel of Spike-specific monoclonal antibodies revealed that the neutralizing activity of some antibodies was dramatically reduced by Spike mutations. In contrast, polyclonal antibodies in the serum of patients infected in early 2020 remained active against most mutated Spike pseudotypes. The majority of serum samples were equally able to neutralize the B.1.1.7 Spike pseudotype, however potency was reduced in a small number of samples (3 of 36) by 5-10-fold. This work highlights that changes in the SARS-CoV-2 Spike PROTEIN can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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