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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (99)

NSP5 (7)

ProteinN (4)

ComplexRdRp (4)

ProteinE (2)


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SARS-CoV-2 Proteins
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    Evolution of ACE2 HGNC and SARS-CoV-2 Interplay Across 247 Vertebrates

    Authors: Zhigang Zhang; Tao Zhang; Qunfu Wu; Yicheng Ma; Wenjing Liu; Chenggang Zou; Ryan Kramer; Christopher Fox; Corey Casper; Christos Hadjichristodoulou; Fani Chatzopoulou; Dimitrios Chatzidimitriou; Periklis Panagopoulos; Panagiota Lourida; Aikaterini Argyraki; Theodoros Lytras; Spyros Sapounas; Gerasimos Gerolymatos; Georgios Panagiotakopoulos; Panagiotis Prezerakos; Sotirios Tsiodras; Vana Sypsa; Angelos Hatzakis; Cleo Anastassopoulou; Nikolaos Spanakis; Athanasios Tsakris; Meletios Athanasios Dimopoulos; Anastasia Kotanidou; Petros Sfikakis; Georgios Kollias; Gkikas Magiorkinis; Dimitrios Paraskevis

    doi:10.1101/2021.01.28.428568 Date: 2021-02-02 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS CoV 2) cause the most serious pandemics of Coronavirus Disease 2019 MESHD (COVID 19), which threatens human health and public safety. SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN ( S) protein PROTEIN uses angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) as recognized receptor for its entry into host cell that contributes to the infection of SARS-CoV-2 MESHD to hosts. Using computational modeling approach, this study resolved the evolutionary pattern of bonding affinity of ACE2 HGNC in 247 jawed vertebrates to the spike (S) protein PROTEIN of SARS-CoV-2. First, high-or-low binding affinity phenotype divergence of ACE2 HGNC to the S protein PROTEIN of SARS-CoV-2 has appeared in two ancient species of jawed vertebrates, Scyliorhinus torazame (low-affinity, Chondrichthyes) and Latimeria chalumnae (high-affinity, Coelacanthimorpha). Second, multiple independent affinity divergence events recur in fishes, amphibians-reptiles, birds, and mammals. Third, high affinity phenotypes go up in mammals, possibly implying the rapid expansion of mammals might accelerate the evolution of coronaviruses. Fourth, we found natural mutations at eight amino acid sites of ACE2 HGNC can determine most of phenotype divergences of bonding affinity in 247 vertebrates and resolved their related structural basis. Moreover, we also identified high-affinity or low-affinity-associated concomitant mutation group.The group linked to extremely high affinity may provide novel potentials for the development of human recombinant soluble ACE2 HGNC (hrsACE2) in treating patients with COVID-19 MESHD or for constructing genetically modified SARS-CoV-2 infection MESHD models promoting vaccines studies. These findings would offer potential benefits for the treatment and prevention of SARS-CoV-2. Keywords: Vertebrates, ACE2 HGNC, SARS-CoV-2, Bonding Affinity

    Computational insights into differential interaction of mamalian ACE2 HGNC with the SARS-CoV-2 spike PROTEIN receptor binding domain

    Authors: Cecylia Severin Lupala; Vikash Kumar; Xiao-dong Su; Haiguang Liu; Wenjing Liu; Chenggang Zou; Ryan Kramer; Christopher Fox; Corey Casper; Christos Hadjichristodoulou; Fani Chatzopoulou; Dimitrios Chatzidimitriou; Periklis Panagopoulos; Panagiota Lourida; Aikaterini Argyraki; Theodoros Lytras; Spyros Sapounas; Gerasimos Gerolymatos; Georgios Panagiotakopoulos; Panagiotis Prezerakos; Sotirios Tsiodras; Vana Sypsa; Angelos Hatzakis; Cleo Anastassopoulou; Nikolaos Spanakis; Athanasios Tsakris; Meletios Athanasios Dimopoulos; Anastasia Kotanidou; Petros Sfikakis; Georgios Kollias; Gkikas Magiorkinis; Dimitrios Paraskevis

    doi:10.1101/2021.02.02.429327 Date: 2021-02-02 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causing agent of the COVID-19 pandemic MESHD, has spread globally. Angiotensin-converting enzyme 2 HGNC (ACE2) has been identified as the host cell receptor that binds to receptor-binding domain (RBD) of the SARS-COV-2 spike protein PROTEIN and mediates cell entry. Because the ACE2 proteins are widely available in mammals, it is important to investigate the interactions between the RBD and the ACE2 of other mammals. Here we analyzed the sequences of ACE2 proteins from 16 mammals and predicted the structures of ACE2-RBD complexes. Analyses on sequence, structure, and dynamics synergistically provide valuable insights into the interactions between ACE2 and RBD. The comparison results suggest that the ACE2 of bovine, cat and panda form strong binding with RBD, while in the cases of rat, least horseshoe bat, horse, pig, mouse and civet, the ACE2 proteins interact weakly with RBD.

    Renin HGNC-Angiotensin System Blockade Influences ACE2 HGNC in Human Type II Pneumocytes

    Authors: Mauro G Silva; Nora L Falcoff; Gerardo C Corradi; José Alfie; Rolando F. Seguel; Gabriela Tabaj; Laura Iglesias; Myriam Nuñez; Gabriela R. Guman; Mariela M. Gironacci

    doi:10.21203/rs.3.rs-159733/v2 Date: 2021-01-27 Source: ResearchSquare

    Rationale— Angiotensin converting enzyme (ACE) 2 HGNC and the transmembrane protease serine 2 HGNC ( TMPRSS2 HGNC) are key for cellular entry of the type 2 coronavirus that causes severe acute respiratory syndrome MESHD (SARS-CoV2), the etiological agent of coronavirus-19 disease MESHD ( COVID-19 MESHD). There has been a growing concern that renin HGNC-angiotensin system (RAS) blockade with ACE HGNC inhibitors (ACEIs) or type 1 angiotensin (Ang II) receptor blockers (ARBs) increases ACE2 HGNC expression and then elevate patient susceptibility to SARS-CoV-2.  However, evidence about RAS blockade and ACE2 HGNC in human lung are lacking.Objective– To investigate RAS blockade on ACE2 HGNC and TMPRSS2 HGNC in type II pneumocytes of human lung parenchymal of untreated and ACEI/ARB-treated hypertensive MESHD subjects.Methods and Results– ACE2 HGNC and TMPRSS2 HGNC protein expression were measured by immunohistochemistry. We found that smoking and RAS blockade influence on the percentage of human ACE2 HGNC-expressing type II pneumocytes (p= 0.026). Smokers subjects under RAS blockade treatment exhibited higher percentage of ACE2 HGNC-expressing type II pneumocytes than normotensive ones. Within the ACEI/ARB-treated group, the percentage of ACE2 HGNC-expressing type II pneumocytes was higher in smokers than never smokers. A significant association between ACE2 HGNC immunostaining intensity and smoking on subjects over 60 years old was found (p= 0.05): older smokers exhibited higher ACE2 HGNC protein levels compared to youngers. The percentage of TMPRSS2 HGNC-expressing type II pneumocytes was greater in men than women (p= 0.026) and in subjects under 60 years old (p= 0.040) and trend to be higher in ACEI/ARB-treated subjects than normotensives (p= 0.060). A significant association between TMPRSS2 HGNC immunostaining intensity with smoking and age or with RAS blockade MESHD and age or with RAS blockade MESHD and smoking was observed. Older or smokers subjects under ACEI/ARB treatment exhibited higher TMPRSS2 HGNC protein levels than youngers or never smokers.Conclusions— ACE2 HGNC and TMPRSS2 HGNC are influenced by smoking and ACEI/ARB treatment. These findings help explain the increased susceptibility to COVID-19 MESHD in subjects with treated cardiovascular-related pathologies. 

    Efficacy of GC-376 against SARS-CoV-2 virus infection MESHD in the K18 hACE2 HGNC transgenic mouse model

    Authors: C. Joaquin Caceres; Stivalis Cardenas-Garcia; Silvia Carnaccini; Brittany Seibert; Daniela S Rajao; Jun Wang; Daniel R Perez; Amanda J. Martinot; Cesar Piedra-Mora; Sidney Beecy; Sarah Ducat; Ronnie Chamanza; Sietske Rosendahl Huber; Leslie van der Fits; Erica N. Borducchi; Michelle Lifton; Jinyan Liu; Felix Nampanya; Shivani Patel; Lauren Peter; Lisa H. Tostanoski; Laurent Pessaint; Alex Van Ry; Brad Finneyfrock; Jason Velasco; Elyse Teow; Renita Brown; Anthony Cook; Hanne Andersen; Mark G. Lewis; Hanneke Schuitemaker; Dan H. Barouch; Christian Lavallee; Pierre-Olivier Hetu; Jean-Sebastien Paquette; Sylvie Levesque; Marieve Cossette; Anna Nozza; Malorie Chabot-Blanchet; Marie-Pierre Dube; Marie-Claude Guertin; Guy Boivin

    doi:10.1101/2021.01.27.428428 Date: 2021-01-27 Source: bioRxiv

    The COVID-19 pandemic MESHD caused by the Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro PROTEIN inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18- hACE2 HGNC mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18- hACE2 HGNC mice and produced milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation MESHD in comparison to vehicle-treated controls, most notably in the brain in mice challenged with a low virus dose. Although GC-376 was not sufficient to improve neither clinical symptoms nor survival, it did show a positive effect against SARS-CoV-2 in vivo. This study supports the notion that the K18- hACE2 HGNC mouse model is suitable to study antiviral therapies against SARS-CoV-2, and GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection MESHD.

    Synthetic nanobody-SARS-CoV-2 receptor-binding domain structures identify distinct epitopes

    Authors: Gennady Verkhivker; Steve Agajanian; Deniz Oztas; Grace Gupta; Deepak Rajpal; Dinesh Kumar; Andra Kusuma Putra; Arif Nur Muhammad Ansori; Muhammad Khaliim Jati Kusala; Mohammad Yusuf Alamudi; Chairul Anwar Nidom

    doi:10.1101/2021.01.27.428466 Date: 2021-01-27 Source: bioRxiv

    The worldwide spread of severe acute respiratory syndrome coronavirus 2 MESHD (SARS CoV 2) demands unprecedented attention. We report four X-ray crystal structures of three synthetic nanobodies (sybodies) (Sb16, Sb45 and Sb68) bind to the receptor-binding domain (RBD) of SARS-CoV-2: binary complexes of Sb16-RBD and Sb45-RBD; a ternary complex of Sb45-RBD-Sb68; and Sb16 unliganded. Sb16 and Sb45 bind the RBD at the ACE2 HGNC interface, positioning their CDR2 HGNC and CDR3 loops diametrically. Sb16 reveals a large CDR2 HGNC shift when binding the RBD. Sb68 interacts peripherally at the ACE2 HGNC interface; steric clashes with glycans explain its mechanism of viral neutralization. Superposing these structures onto trimeric spike (S) protein PROTEIN models indicates these sybodies bind conformations of the mature S protein PROTEIN differently, which may aid therapeutic design.

    Potent Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) by photosensitizers

    Authors: Shujuan Yu; Gaohui Sun; Yaqun Sui; Hanlin Li; Ning Zhang; Yuhai Bi; George Gao; Longguang Jiang; Peng Xu; Cai Yuan; Yang Yang; Mingdong Huang

    doi:10.21203/rs.3.rs-152985/v1 Date: 2021-01-22 Source: ResearchSquare

    The pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has exploded since December 2019, and causes more than 2 million death MESHD with more than 95 million people infected as of Jan. 21th, 2021 globally1,2. Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), expressed in the lungs, arteries, heart, kidney, intestines, and nasal epithelium3, has been shown to be the primary entry point targeted by the surface spike protein PROTEIN of SARS-CoV-2. Currently, no proven antiviral treatment for SARS-CoV-2 infection MESHD is available. In this study, we screened a number of photosensitizers for photodynamic viral inactivation, and found compounds pentalysine β-carbonylphthalocyanine zinc (ZnPc5K) and chlorin e6 (ce6) potently inhibited the viral infection and replication in vitro with half-maximal effective concentrations (EC50) values at nanomolar level. Such viral inactivation strategy is implementable, and has unique advantages, including resistance to virus mutations, affordability compared to the monoclonal antibodies, and lack of long-term toxicity MESHD.

    A Super-Potent Tetramerized ACE2 HGNC Protein Displays Enhanced Neutralization of SARS-CoV-2 Virus Infection MESHD

    Authors: Ami Miller; Adam Leach; Jemima Thomas; Emma Bentley; Giada Mattiuzzo; Lijo John; Ali Mirazimi; Gemma Harris; Nadisha Nadisha Gamage; Stephen Carr; Hanif Ali; Rob Van Montfort; Terence Rabbitts; Craig McAndrew

    doi:10.21203/rs.3.rs-151560/v1 Date: 2021-01-20 Source: ResearchSquare

    Approaches are needed for therapy of the severe acute respiratory syndrome MESHD from SARS-CoV-2 coronavirus MESHD ( COVID-19 MESHD). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 HGNC (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviruses into human cells. We have implemented a novel protein engineering technology to produce a super-potent tetravalent form of ACE2 HGNC, coupled to the human immunoglobulin g1 Fc region, using a self-assembling, tetramerization domain from p53 HGNC protein. This high molecular weight Quad protein ( ACE2 HGNC-Fc-TD) retains binding to the SARS-CoV-2 receptor binding spike protein PROTEIN and can form a complex with the spike protein PROTEIN plus anti-viral antibodies. The ACE2 HGNC-Fc-TD acts as a powerful decoy protein that out-performs soluble monomeric and dimeric ACE2 HGNC proteins and blocks both SARS-CoV-2 pseudovirus and SARS-CoV-2 virus infection MESHD with greatly enhanced efficacy. The ACE2 HGNC tetrameric protein complex promise to be important for development as decoy therapeutic proteins against COVID-19 MESHD. In contrast to monoclonal antibodies, ACE2 HGNC decoy is unlikely to be affected by mutations in SARS-CoV-2 that are beginning to appear in variant forms. In addition, ACE2 HGNC multimeric proteins will be available as therapeutic proteins should new coronaviruses appear in the future because these are likely to interact with ACE2 HGNC receptor.

    GRP78 HGNC binds SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein and ACE2 HGNC and GRP78 HGNC depleting antibody blocks viral entry and infection in vitro

    Authors: Anthony J Carlos; Dat P Ha; Da-Wei Yeh; Richard Van Krieken; Parkash Gill; Keigo Machida; Amy Lee; Faisal M Al Ahbabi; Yasser S Mohammed; Nasser M Al Falasi; Noor M Almheiri; Sumaya M Al Blooshi; Quentin Muzzin; Loic Desquilbet; Larissa Thackray; Michael D Diamond; James E. Crowe

    doi:10.1101/2021.01.20.427368 Date: 2021-01-20 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causative agent of the current COVID-19 MESHD global pandemic, utilizes the host receptor angiotensin-converting enzyme 2 ( ACE2 HGNC) for viral entry. However, other host factors may also play major roles in viral infection MESHD. Here we report that the stress-inducible molecular chaperone GRP78 HGNC can form a complex with the SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein and ACE2 HGNC intracellularly and on the cell surface, and that the substrate binding domain of GRP78 HGNC is critical for this function. Knock-down of GRP78 HGNC by siRNA dramatically reduced cell surface ACE2 HGNC expression. Treatment of lung epithelial cells with a humanized monoclonal antibody (hMAb159), selected for its ability to cause GRP78 HGNC endocytosis and its safe clinical profile in preclinical models, reduces cell surface ACE2 HGNC expression, SARS-CoV-2 Spike PROTEIN-driven viral entry, and significantly inhibits SARS-CoV-2 infection MESHD in vitro. Our data suggest that GRP78 HGNC is an important host auxiliary factor for SARS-CoV-2 entry and infection MESHD and a potential target to combat this novel pathogen and other viruses that utilize GRP78 HGNC.

    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.

    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.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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