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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (719)

NSP5 (34)

ProteinN (30)

ProteinS1 (27)

ComplexRdRp (23)


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SARS-CoV-2 Proteins
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    Massively Multiplexed Affinity Characterization of Therapeutic Antibodies Against SARS-CoV-2 Variants

    Authors: Emily Engelhart; Randolph Lopez; Ryan Emerson; Charles Lin; Colleen Shikany; Daniel Guion; Mary Kelley; David Younger

    doi:10.1101/2021.04.27.440939 Date: 2021-04-28 Source: bioRxiv

    Antibody therapies represent a valuable tool to reduce COVID-19 MESHD deaths MESHD and hospitalizations. Multiple antibody candidates have been granted emergency use authorization by the FDA and many more are in clinical trials. Most antibody therapies for COVID-19 MESHD are engineered to bind to the receptor-binding domain (RBD) of the SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein and disrupt its interaction with ACE2 HGNC. Notably, several SARS-CoV-2 strains have accrued mutations throughout the RBD that improve ACE2 HGNC binding affinity, enhance viral transmission, and escape some existing antibody therapies. Here, we measure the binding affinity of 33 therapeutic antibodies against a large panel of SARS-CoV-2 variants and related strains of clinical significance to determine epitopic residues, determine which mutations result in loss of binding, and predict how future RBD variants may impact antibody efficacy.

    SARS-COV-2 induced Diarrhea MESHD is inflammatory, Ca2+ Dependent and involves activation of calcium activated Cl channels

    Authors: Mark Donowitz; Chung-Ming Tse; Karol Dokladny; Manmeet Rawat; Ivy Hurwitz; Chunyan Ye; Alison Kell; Ruxian Lin; Sun Lee; Chenxu Guo Guo; Shang Jui Tsai; Andrea Cox; Stephen Gould; Julie In; Steven B Bradfute; Nicholas Zachos; Olga Kovbasnjuk

    doi:10.1101/2021.04.27.441695 Date: 2021-04-28 Source: bioRxiv

    Diarrhea MESHD occurs in 2-50% of cases of COVID-19 MESHD (~8% is average across series). The diarrhea MESHD does not appear to account for the disease mortality and its contribution to the morbidity has not been defined, even though it is a component of Long Covid or post-infectious aspects of the disease. Even less is known about the pathophysiologic mechanism of the diarrhea MESHD. To begin to understand the pathophysiology of COVID-19 MESHD diarrhea MESHD, we exposed human enteroid monolayers obtained from five healthy subjects and made from duodenum, jejunum, and proximal colon MESHD to live SARS-CoV-2 and virus like particles (VLPs) made from exosomes expressing SARS-CoV-2 structural proteins (Spike PROTEIN, Nucleocapsid, Membrane and Envelope). Results: 1) Live virus was exposed apically for 90 min, then washed out and studied 2 and 5 days later. SARS-Cov-2 was taken up by enteroids and live virus was present in lysates and in the apical>>basolateral media of polarized enteroids 48 h after exposure. This is the first demonstration of basolateral appearance of live virus after apical exposure. High vRNA concentration was detected in cell lysates and in the apical and basolateral media up to 5 days after exposure. 2 ) Two days after viral exposure, cytokine measurements of media showed significantly increased levels of IL-6 HGNC, IL-8 HGNC and MCP-1. 3) Two days after viral exposure, mRNA levels of ACE2 HGNC, NHE3 HGNC and DRA HGNC were reduced but there was no change in mRNA of CFTR HGNC. NHE3 HGNC protein was also decreased. 4) Live viral studies were mimicked by some studies with VLP exposure for 48 h. VLPs with Spike- D614G bound to the enteroid apical surface and was taken up; this resulted in decreased mRNA levels of ACE2 HGNC, NHE3 HGNC, DRA HGNC and CFTR HGNC. 4) VLP effects were determined on active anion secretion measured with the Ussing chamber/voltage clamp technique. S-D614G acutely exposed to apical surface of human ileal enteroids did not alter the short-circuit current (Isc). However, VLPS- D614G exposure to enteroids that were pretreated for ~24 h with IL-6 HGNC plus IL-8 HGNC induced a concentration dependent increase in Isc indicating stimulated anion secretion, that was delayed in onset by ~8 min . The anion secretion was inhibited by apical exposure to a specific calcium activated Cl channel ( CaCC HGNC) inhibitor (AO1) but not by a specific CFTR HGNC inhibitor (BP027); was inhibited by basolateral exposure to the K channel inhibit clortimazole; and was prevented by pretreatment with the calcium buffer BAPTA-AM. 5) The calcium dependence of the VLP-induced increase in Isc was studied in Caco- 2/BBe cells stably expressing the genetically encoded Ca2+ sensor GCaMP6s. 24 h pretreatment with IL-6 HGNC/ IL-8 HGNC did not alter intracellular Ca2+. However, in IL-6 HGNC/ IL-8 HGNC pretreated cells, VLP S-D614G caused appearance of Ca2+waves and an overall increase in intracellular Ca2+ with a delay of ~10 min after VLP addition. We conclude that the diarrhea MESHD of COVID-19 MESHD appears to an example of a calcium dependent inflammatory diarrhea MESHD that involves both acutely stimulated Ca2+ dependent anion secretion (stimulated Isc) that involves CaCC HGNC and likely inhibition of neutral NaCl absorption (decreased NHE3 HGNC protein and mRNA and decreased DRA HGNC mRNA).

    Regulation of Lysosome-Associated Membrane Protein 3 ( LAMP3 HGNC) in Lung Epithelial Cells by Coronaviruses (SARS-CoV-1/2) and Type I Interferon Signaling MESHD

    Authors: Ramana Chilakamarti

    doi:10.1101/2021.04.28.441840 Date: 2021-04-28 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major risk factor for mortality and morbidity in critical care hospitals around the world. Lung epithelial type II cells play a major role in several physiological processes, including recognition and clearance of respiratory viruses as well as repair of lung injury MESHD in response to environmental toxicants. Gene expression profiling of lung epithelial type II-specific genes led to the identification of lysosomal-associated membrane protein 3 HGNC ( LAMP3 HGNC). Intracellular locations of LAMP3 HGNC include plasma membrane, endosomes, and lysosomes. These intracellular organelles are involved in vesicular transport and facilitate viral entry and release of the viral RNA into the host cell cytoplasm. In this study, regulation of LAMP3 HGNC expression in human lung epithelial cells by several respiratory viruses and type I interferon signaling was investigated. Coronaviruses including SARS-CoV-1 and SARS-CoV-2 MESHD significantly induced LAMP3 HGNC expression in lung epithelial cells within 24 hours after infection that required the presence of ACE2 HGNC viral entry receptor. Time-course experiments revealed that the induced expression of LAMP3 HGNC by SARS-CoV-2 was correlated with the induced expression of interferon-beta1 HGNC ( IFNB1 HGNC) and signal transducers and activator of transcription 1 ( STAT1 HGNC) mRNA levels. LAMP3 HGNC was also induced by direct IFN-beta treatment or by infection with influenza virus lacking the non-structural protein1(NS1) in NHBE bronchial epithelial cells. LAMP3 HGNC expression was induced in human lung epithelial cells by several respiratory viruses, including respiratory syncytial virus MESHD ( RSV MESHD) and the human parainfluenza virus 3 (HPIV3). Location in lysosomes and endosomes as well as induction by respiratory viruses and type I Interferon suggests that LAMP3 HGNC may have an important role in inter-organellar regulation of innate immunity and a potential target for therapeutic modulation in health and disease. Furthermore, bioinformatics revealed that a subset of lung type II cell genes were differentially regulated in the lungs of COVID-19 MESHD patients.

    Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drive rapid and potent immunogenicity capable of single-dose protection

    Authors: Kylie Konrath; Kevin Liaw; Yuanhan Wu; Xizhou Zhu; Susanne Walker; Ziyang Xu; Katherine Schultheis; Neethu Chokkalingam; Nicholas J Tursi; Jianqiu Du; Matthew Sullivan; Mansi Purwar; Alan Moore; Viviane Machado; Igor Maricic; Emma Reuschel; Drew Frase; Christel Iffland; Kate Broderick; Laurent Humeau; Trevor Smith; Jesper Pallesen; David B Weiner; Daniel W Kulp

    doi:10.1101/2021.04.28.441474 Date: 2021-04-28 Source: bioRxiv

    Antibodies from SARS-CoV-2 vaccines may target epitopes which reduce durability or increase the potential for escape from vaccine-induced immunity. Using a novel synthetic vaccinology pipeline, we developed rationally immune focused SARS-CoV-2 Spike PROTEIN-based vaccines. N-linked glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and comprehensive in vitro screening, we incorporated glycans into the Spike Receptor-Binding Domain (RBD) and assessed antigenic profiles. We developed glycan coated RBD immunogens and engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicited potent neutralizing antibodies in guinea pigs, hamsters and multiple mouse models, including human ACE2 HGNC and human B cell repertoire transgenics. RBD nanoparticles encoding wild-type and the P.1 SARS-CoV-2 variant induced high levels of cross-neutralizing antibodies. Single, low dose immunization protected against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of novel, potent coronavirus vaccines.

    EVIDENCE FOR BIOLOGICAL AGE ACCELERATION AND TELOMERE2 SHORTENING IN COVID-19 MESHD SURVIVORS

    Authors: Alessia Mongelli; carlo gaetano; michela gottardi zamperla; veronica barbi; sandra atlante; maria teresa la rovere; tiziana bachetti; oronzo catalano; maurizio bussotti; laura della vecchia; simona nanni; antonella farsetti; fabio martelli

    doi:10.1101/2021.04.23.21255973 Date: 2021-04-27 Source: medRxiv

    Introduction & Background: the SARS-CoV-2 infection MESHD determines the COVID-19 MESHD syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis MESHD,inflammatory cytokines release, and immunodepression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called post- COVID19 MESHD syndrome (PPCS) is a common finding. In patients who survived the SARS-CoV-2 infection MESHD, overt PPCS presents one or more symptoms such as fatigue MESHD, dyspnea MESHD, memory loss MESHD, sleep disorders MESHD, and difficulty concentrating. The pathophysiology of PPCS is currently poorly understood, and whether epigenetic mechanisms are involved in this process is unexplored. Methods & Results: In this study, a cohort of 117 COVID19 MESHD survivors (post- COVID19 MESHD) and 144 non-infected volunteers ( COVID19 MESHD-free) were analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. Besides, telomere length (TL) and ACE2 HGNC and DPP4 HGNC receptor expression were determined. The results show a consistent biological age increase in the post-covid population (mean 58,44 DS 14,66 ChronoAge Vs. mean 67,18 DS 10,86 BioAge, P<0,0001), determining a DeltaAge acceleration of 10,45 DS 7,29 years (+5.25 years above range of normality) compared to 3,68 DS 8,17 years for the COVID19 MESHD-free population (P<0,0001). A significant telomere shortening parallels this finding in the post- COVID19 MESHD cohort compared to COVID19 MESHD-free subjects (post- COVID19 MESHD TL: 3,03 DS 2,39 Kb vs. COVID19 MESHD-free: 10,67 DS 11,69 Kb; P<0,0001). Additionally, ACE2 HGNC expression was decreased in post- COVID19 MESHD patients compare to COVID19 MESHD-free, while DPP-4 HGNC did not change. Conclusion: In light of these observations, we hypothesize that some epigenetic alterations are associated with the post- COVID19 MESHD condition, particularly in the younger (<60 years). Although the consequences of such modifications on the long-term clinical outcome remain unclear, they might 46 indicate a direction to investigate the pathophysiological basis of the post- COVID19 MESHD syndrome

    Binding mechanism of neutralizing Nanobodies targeting SARS-CoV-2 Spike Glycoprotein MESHD SARS-CoV-2 Spike Glycoprotein PROTEIN

    Authors: Mert Golcuk; Aysima Hacisuleyman; Burak Erman; Ahmet Yildiz; Mert Gur

    doi:10.1101/2021.04.23.441186 Date: 2021-04-26 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human cells upon binding of its spike ( S) glycoproteins PROTEIN to ACE2 HGNC receptors. Several nanobodies neutralize SARS-CoV-2 infection MESHD by binding to the receptor-binding domain (RBD) of S protein PROTEIN, but the underlying mechanism is not well understood. Here, we identified an extended network of pairwise interactions between RBD and nanobodies H11-H4, H11-D4, and Ty1 by performing all-atom molecular dynamics ( MD MESHD) simulations. Simulations of the nanobody-RBD- ACE2 HGNC complex revealed that H11-H4 more strongly binds to RBD without overlapping with ACE2 HGNC and triggers dissociation of ACE2 HGNC due to electrostatic repulsion. In comparison, Ty1 binding results in dissociation of ACE2 HGNC from RBD due to an overlap with the ACE2 HGNC binding site, whereas H11-D4 binding does not trigger ACE2 HGNC dissociation. Mutations in SARS-CoV-2 501Y.V1 and 501.V2 variants resulted in a negligible effect on RBD- ACE2 HGNC binding. However, the 501.V2 variant weakened H11-H4 and H11-D4 binding while strengthening Ty1 binding to RBD. Our simulations indicate that all three nanobodies can neutralize 501Y.V1 while Ty1 is more effective against the 501.V2 variant.

    A potently neutralizing anti-SARS-CoV-2 antibody inhibits variants of concern by binding a highly conserved epitope

    Authors: Laura VanBlargan; Lucas Adams; Zhuoming Liu; Rita E Chen; Pavlo Gilchuk; Saravanan Raju; Brittany Smith; Haiyan Zhao; James Brett Case; Emma S Winkler; Bradley Whitener; Lindsay Droit; Ismael Aziati; Pei-Yong Shi; Adrian Creanga; Amarendra Pegu; Scott Handley; David Wang; Adrianus Boon; James E. Crowe; Sean P. J. Whelan; Daved Fremont; Michael Diamond

    doi:10.1101/2021.04.26.441501 Date: 2021-04-26 Source: bioRxiv

    With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of neutralizing anti-SARS-CoV-2 mAbs that bind the receptor binding domain of the spike protein PROTEIN at distinct epitopes and block virus attachment to cells and its receptor, human angiotensin converting enzyme-2 HGNC ( hACE2 HGNC). While several potently neutralizing mAbs protected K18- hACE2 HGNC transgenic mice against infection caused by historical SARS-CoV-2 strains, others induced escape variants in vivo and lost activity against emerging strains. We identified one mAb, SARS2-38, that potently neutralizes all SARS-CoV-2 variants of concern tested and protects mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engages a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of inhibitory antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.

    Broad cross-reactivity across sarbecoviruses exhibited by a subset of COVID-19 MESHD donor-derived neutralizing antibodies

    Authors: Claudia A Jette; Alexander A Cohen; Priyanthi N. P. Gnanapragasam; Frauke Muecksch; Yu E. Lee; Kathryn E. Huey-Tubman; Fabian Schmidt; Theodora Hatziioannou; Paul D. Bieniasz; Michel C. Nussenzweig; Anthony P West; Jennifer R. Keeffe; Pamela Bjorkman; Christopher O Barnes

    doi:10.1101/2021.04.23.441195 Date: 2021-04-26 Source: bioRxiv

    Many anti-SARS-CoV-2 neutralizing antibodies target the ACE2 HGNC-binding site on viral spike receptor-binding domains (RBDs). The most potent antibodies recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD antibodies against a less-exposed, but more-conserved, cryptic epitope could recognize newly-emergent zoonotic sarbecoviruses and variants, but usually show only weak neutralization potencies. We characterized two class 4 anti-RBD antibodies derived from COVID-19 MESHD donors that exhibited broad recognition and potent neutralization of zoonotic coronavirus and SARS-CoV-2 variants. C118-RBD and C022-RBD structures revealed CDRH3 mainchain H-bond interactions that extended an RBD {beta}-sheet, thus reducing sensitivity to RBD sidechain changes, and epitopes that extended from the cryptic epitope to occlude ACE2 HGNC binding. A C118-spike trimer structure revealed rotated RBDs to allow cryptic epitope access MESHD and the potential for intra-spike crosslinking to increase avidity. These studies facilitate vaccine design and illustrate potential advantages of class 4 RBD-binding antibody therapeutics.

    A SARS CoV-2 nucleocapsid vaccine protects against distal viral dissemination

    Authors: Jacob Class; Tanushree Dangi; Justin Richner; Pablo Penaloza-MacMaster

    doi:10.1101/2021.04.26.440920 Date: 2021-04-26 Source: bioRxiv

    The SARS CoV-2 pandemic has killed millions of people. This viral infection can also result in substantial morbidity, including respiratory insufficiency MESHD and neurological manifestations, such as loss of smell and psychiatric diseases MESHD. Most SARS CoV-2 vaccines are based on the spike antigen, and although they have shown extraordinary efficacy at preventing severe lung disease MESHD and death MESHD, they do not always confer sterilizing immune protection. We performed studies in K18- hACE2 HGNC mice to evaluate whether the efficacy of SARS CoV-2 vaccines could be augmented by incorporating nucleocapsid as a vaccine antigen. We vaccinated mice with adenovirus-based vaccines encoding spike antigen alone, nucleocapsid antigen alone, or combined spike and nucleocapsid antigens. Mice were then challenged intranasally with SARS CoV-2, and acute viral loads were quantified at a proximal site of infection (lung) and a distal site of infection (brain). Interestingly, the spike-based vaccine conferred acute protection in the lung, but not in the brain. The spike-based vaccine conferred acute protection in the brain only if combined with the nucleocapsid-based vaccine. These findings suggest that nucleocapsid-specific immunity is important for the distal control of SARS CoV-2, warranting the inclusion of nucleocapsid in next-generation COVID-19 MESHD vaccines.

    Transmission characteristics of SARS-CoV-2 variants of concern: Rapid Scoping Review

    Authors: Janet A Curran; Justine Dol; Leah Boulos; Mari Somerville; Jason LeBlanc; Lisa Barrett; Jeannette Comeau; Bearach Reynolds; Holly McCulloch; Marilyn MacDonald; Danielle Shin; Allyson Gallant; Helen Wong; Daniel Crowther; Ziwa Yu

    doi:10.1101/2021.04.23.21255515 Date: 2021-04-25 Source: medRxiv

    Background: As of March 2021, three SARS-CoV-2 variants of concern (VOC) have been identified (B.1.1.7, B.1.351 and P.1 HGNC) and been detected in over 111 countries. Despite their widespread circulation, little is known about their transmission characteristics. There is a need to understand current evidence on VOCs before practice and policy decisions can be made. This study aimed to map the evidence related to the transmission characteristics of three VOCs. Methods: A rapid scoping review approach was used. Seven databases were searched on February 21, 2021 for terms related to VOCs, transmission, public health and health systems. A grey literature search was conducted on February 26, 2021. Title/abstracts were screened independently by one reviewer, while full texts were screened in duplicate. Data were extracted using a standardized form which was co-developed with infectious disease MESHD experts. A second data extractor verified the results. Studies were included if they reported on at least one of the VOCs and transmissibility. Animal studies and modeling studies were excluded. The final report was reviewed by content experts. Results: Of the 1796 articles and 67 grey literature sources retrieved, 16 papers and 7 grey sources were included. Included studies used a wide range of designs and methods. The majority (n=20) reported on B.1.1.7. Risk of transmission, reported in 15 studies, was 45-71% higher for B.1.1.7 compared to non-VOCs, while R0 was 75-78% higher and the reported Rt ranged from 1.1-2.8. There was insufficient evidence on the transmission risk of B.1.35.1 and P.1 HGNC. Twelve studies discussed the mechanism of transmission of VOCs. Evidence suggests an increase in viral load among VOCs based on cycle threshold values, and possible immune evasion due to increased ACE2 HGNC binding capacity of VOCs. However, findings should be interpreted with caution due to the variability in study designs and methods. Conclusion: VOCs appear to be more transmissible than non-VOCs, however the mechanism of transmission is unclear. With majority of studies focusing on the B.1.1.7 VOC, more research is needed to build upon these preliminary findings. It is recommended that decision-makers continue to monitor VOCs and emerging evidence on this topic to inform public health policy.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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