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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (17)

NSP5 (2)

ProteinN (1)


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    Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants

    Authors: Christy L. Lavine; Shaun Rawson; Haisun Zhu; Krishna Anand; Pei Tong; Avneesh Gautam; Shen Lu; Sarah Sterling; Richard M Walsh Jr.; Jianming Lu; Wei Yang; Michael S Seaman

    doi:10.1101/2021.04.13.439709 Date: 2021-04-14 Source: bioRxiv

    Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) have become the dominant circulating strains that continue to fuel the COVID-19 pandemic MESHD despite intensive vaccination efforts throughout the world. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Mutations in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). The enhanced receptor engagement can account for the increased transmissibility and risk of mortality as the variant may begin to infect efficiently infect MESHD additional cell types expressing low levels of ACE2 HGNC. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein PROTEIN, rendering complete resistance to some potent neutralizing antibodies. These findings provide structural details on how the wide spread of SARS-CoV-2 enables rapid evolution to enhance viral fitness MESHD and immune evasion. They may guide intervention strategies to control the pandemic.

    mRNA vaccination compared to infection elicits an IgG-predominant response with greater SARS-CoV-2 specificity and similar decrease in variant spike recognition

    Authors: Katharina Roeltgen; Sandra C.A. Nielsen; Prabhu S Arunachalam; Fan Yang; Ramona A. Hoh; Oliver F. Wirz; Alexandra S Lee; Fei Gao; Vamsee Mallajosyula; Chunfeng Li; Emily Haraguchi; Massa J Shoura; James L Wilbur; Jacob N. Wohlstadter; Mark M. Davis; Benjamin A. Pinsky; George B. Sigal; Bali Pulendran; Kari C. Nadeau; Scott D. Boyd

    doi:10.1101/2021.04.05.21254952 Date: 2021-04-07 Source: medRxiv

    During the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike PROTEIN protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected MESHD patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 MESHD patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected MESHD patients exposed to Wuhan-Hu-1 antigens.

    Multiplex Antibody Analysis of IgM, IgA HGNC and IgG to SARS-CoV-2 in Saliva and Serum from Infected Children and their Close Contacts

    Authors: Carlota Dobano; Selena Alonso; Marta Vidal; Alfons Jimenez; Rocio Rubio; Rebeca Santano; Diana Barrios; Gemma Pons Tomas; Maria Mele Casas; Maria Hernandez Garcia; Monica Girona-Alarcon; Laura Puyol; Natalia Rodrigo Melero; Carlo Carolis; Aleix Garcia-Miquel; Elisenda Bonet-Carne; Joana Claverol; Marta Cubells; Claudia Fortuny; Victoria Fumado; Anna Codina; Quique Bassat; Carmen Munoz-Almagro; Mariona Fernandez de Sevilla; Eduard Gratacos; Luis Izquierdo; Juan Jose Garcia-Garcia; Ruth Aguilar; Iolanda Jordan; Gemma Moncunill

    doi:10.1101/2021.03.22.21254120 Date: 2021-03-26 Source: medRxiv

    COVID-19 MESHD affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of the coronavirus in pediatric populations and guide public health interventions. We evaluated the utility of high-throughput Luminex-based assays applied to saliva samples to quantify IgM, IgA HGNC and IgG antibodies against five SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S) and nucleocapsid (N PROTEIN) antigens in the context of a contacts and infectivity longitudinal MESHD study. We compared the antibody levels obtained in saliva versus serum/plasma samples from a group of children and adults tested weekly by RT-PCR over 35 days and diagnosed as positive (n=58), and a group of children and adults who consistently tested negative over the follow up period (n=61), in the Summer of 2020 in Barcelona, Spain. Antibody levels in saliva samples from individuals with confirmed RT-PCR diagnosis of SARS-CoV-2 infection MESHD were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Higher levels of anti-S IgG were found in asymptomatic individuals that could indicate protection against disease in infected MESHD individuals. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa, and therefore that both measurements are complementary. In addition to serum/plasma, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to better estimate the percentage of individuals who have experienced coronavirus infection MESHD. Saliva antibody detection could allow determining COVID-19 MESHD prevalence in pediatric populations, alternative to bleeding MESHD or nasal swab, and serological diagnosis following vaccination.

    Preliminary Efficacy of the NVX-CoV2373 Covid-19 MESHD Vaccine Against the B.1.351 Variant

    Authors: Vivek Shinde; Sutika Bhikha; Zaheer Hossain; Moherndran Archary; Qasim Bhorat; Lee Fairlie; Umesh Lalloo; Mduduzi Lawrance Sandile Masilela; Dhayendre Moodley; Sherika Hanley; Leon Fouche; Cheryl Louw; Michele Tameris; Nishanta Singh; Ameena Goga; Keertan Dheda; Coert Grobbelaar; Gertruida Kruger; Nazira Carrim-Ganey; Vicky Baillie; Tulio de Oliveira; Anthonet Lombard Koen; Jonah J Lombaard; Rosie Mngqibisa; As'ad Ebrahim Bhorat; Gabriella Benade; Natasha Lalloo; Annah Pitsi; Pieter-Louis Vollgraaff; Angelique Luabeya; Aliasgar Esmail; Friedrich G. Petrick; Aylin Oommen Jose; Sharne Foulkes; Khatija Ahmed; Asha Thombrayil; Lou Fries; Shane Cloney-Clark; Mingzhu Zhu; Chijioke Bennett; Gary Albert; Emmanuel Faust; Joyce Plested; Andreana Robertson; Susan Neal; Iksung Cho; Gregory M. Glenn; Filip Dubovsky; Shabir Madhi

    doi:10.1101/2021.02.25.21252477 Date: 2021-03-03 Source: medRxiv

    Background The emergence of severe acute respiratory syndrome coronavirus 2 MESHD (SARS CoV-2) variants threatens progress toward control of the Covid-19 pandemic MESHD. Evaluation of Covid-19 MESHD vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform vaccine development and use. Methods In this phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa, healthy human immunodeficiency MESHD virus (HIV)-negative adults (18 to 84 years) or medically stable people living with HIV MESHD (PLWH) (18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21 days apart, of either NVX-CoV2373 nanoparticle vaccine (5 micrograms recombinant spike protein PROTEIN with 50 micrograms Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy greater than or equal to 7 days following the second dose against laboratory-confirmed symptomatic Covid-19 MESHD in previously SARS-CoV-2 uninfected participants. Results A total of 4387 participants were randomized and dosed at least once, 2199 with NVX CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive at baseline. Among 2684 baseline seronegative participants (94% HIV negative; 6% PLWH), there were 15 and 29 predominantly mild to moderate Covid-19 MESHD cases in NVX CoV2373 and placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval [CI]: 6.1 to 72.8). Efficacy in HIV negative participants was 60.1% (95% CI: 19.9 to 80.1), and did not differ by baseline serostatus. Of the primary endpoint cases with available whole genome sequencing, 38 (92.7%) of 41 were the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI: -0.6 to 76.2) in HIV-negative participants. Among placebo recipients, the incidence of symptomatic Covid-19 MESHD was similar in baseline seronegative vs baseline seropositive participants during the first 2 months of follow-up (5.3% vs 5.2%). Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX CoV2373; serious adverse events were rare in both groups. Conclusions The NVX-CoV2373 vaccine was efficacious in preventing Covid-19 MESHD, which was predominantly mild to moderate and due to the B.1.351 variant, while evidence of prior infection MESHD with the presumptive original SARS CoV-2 did not confer protection against probable B.1.351 disease. (Funded by Novavax, The Bill and Melinda Gates Foundation, and the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04533399)

    Discovery of SARS-CoV-2 strain of P.1 lineage harboring K417T/ E484K / N501Y by whole genome sequencing in the city, Japan

    Authors: Yosuke Hirotsu; Masao Omata

    doi:10.1101/2021.02.24.21251892 Date: 2021-02-26 Source: medRxiv

    On the February 2020, the very first case was an American female from Diamond Princess cruise ship HGNC. Since, we have confirmed 136 patients infected with coronavirus disease 2019 MESHD ( COVID-19 MESHD) until February 2021. Here, we conducted the whole genome sequencing analysis of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) on samples from 70 of 136 patients (51.5%). These patients were infected MESHD in Diamond Princess cruise ship HGNC (n=1), Africa (n=2), Japan (n=66) and Brazil (n=1). The viral genome sequence of a patient on the Diamond Princess cruise ship HGNC in February 2020 was similar to that of original strain found in Wuhan, China (19A clade). Four patients, including two returnees from Africa and two lived in Japan, confirmed at the end of March 2020 had sequences similar to those of lineage with D614G mutation, which was endemic in Europe (20A [n=3] and 20B [n=1] clade). The 64 Japanese patients confirmed from September 2020 to January 2021 had sequences similar to those of the currently prevalent lineage (20B [n=58] and 20C clade [n=6]). Subsequent analysis revealed three mutations (K417T/ E484K / N501Y) in the receptor binding domain of the spike protein PROTEIN in a man in his 40s. The sequence was identical to the P.1 lineage (also known as 20J/501Y.V3) reported in Brazil. This is the first report of SARS-CoV-2 P. MESHD1 lineage identified in the city, Japan.

    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/v4 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 µM) and v iral infection MESHD([EC50] = 4.4 µM), 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.

    SARS-CoV-2 infection MESHD induces long-lived bone marrow plasma cells in humans

    Authors: Ali Ellebedy; Jackson Turner; Wooseob Kim; Elizaveta Kalaidina; Charles Goss; Adriana Rauseo; Aaron Schmitz; Lena Hansen; Alem Haile; Michael Klebert; Iskra Pusic; Jane O’Halloran; Rachel Presti

    doi:10.21203/rs.3.rs-132821/v1 Date: 2020-12-20 Source: ResearchSquare

    Infection or vaccination induces a population of long-lived bone marrow plasma cells (BMPCs) that are a persistent and essential source of protective antibodies1–5. Whether this population is induced in patients infected MESHD with the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is unknown. Recent reports have suggested that SARS-CoV-2 convalescent patients experience a rapid decay in their antigen-specific serum antibodies, raising concerns that humoral immunity against this virus may be short-lived6–8. Here we show that in patients who experienced mild infections (n=73), serum anti- SARS-CoV-2 spike PROTEIN (S) antibodies indeed decline rapidly in the first 3 to 4 months after infection. However, this is followed by a more stable phase between 4- and 8-months after infection with a slower serum anti-S antibody decay rate. The level of serum antibodies correlated with the frequency of S-specific long-lived BMPCs obtained from 18 SARS-CoV-2 convalescent patients 7 to 8 months after infection. S-specific BMPCs were not detected in aspirates from 11 healthy subjects with no history of SARS-CoV-2 infection MESHD. Comparable frequencies of BMPCs specific to contemporary influenza virus antigens or tetanus MESHD and diphtheria vaccine antigens were present in aspirates in both groups. Circulating memory B cells ( MBCs MESHD) directed against the S protein PROTEIN were detected in the SARS-CoV-2 convalescent patients but not in uninfected controls, whereas both groups had MBCs MESHD against influenza virus hemagglutinin. Overall, we show that robust antigen specific long-lived BMPCs and MBCs MESHD are induced after mild SARS-CoV-2 infection MESHD of humans.

    Molecular basis of the logical evolution of the novel coronavirus SARS-CoV-2: A comparative analysis

    Authors: Abhisek Dwivedy; Krushnachandra Murmu; Mohammed Ahmad; Punit Prasad; Bichitra Biswal; Palok Aich; Ya-Nan Dai; Haiyan Zhao; Lucas Adams; Michael Holtzman; Adam Bailey; James Brett Case; Daved Fremont; Robyn S Klein; Michael Diamond; Adrianus Boon

    doi:10.1101/2020.12.03.409458 Date: 2020-12-03 Source: bioRxiv

    A novel disease, COVID-19 MESHD, is sweeping the world since end of 2019. While in many countries, the first wave is over, but the pandemic is going through its next phase with a significantly higher infectability MESHD. COVID-19 MESHD is caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) that seems to be more infectious than any other previous human coronaviruses. To understand any unique traits of the virus that facilitate its entry into the host, we compared the published structures of the viral spike protein PROTEIN of SARS-CoV-2 with other known coronaviruses to determine the possible evolutionary pathway leading to the higher infectivity. The current report presents unique information regarding the amino acid residues that were a) conserved to maintain the binding with ACE2 HGNC ( Angiotensin-converting enzyme 2 HGNC), and b) substituted to confer an enhanced binding affinity and conformational flexibility to the SARS-CoV-2 spike PROTEIN protein. The present study provides novel insights into the evolutionary nature and molecular basis of higher infectability MESHD and perhaps the virulence of SARS-CoV-2.

    Computational Modeling Indicates A Decreased Affinity of SARS-CoV-2 to ACE2 HGNC by Steroids

    Authors: Alireza Mansouri; Rasoul Kowsar; Khaled Sadeghi; Akio Miyamoto

    doi:10.21203/rs.3.rs-86139/v1 Date: 2020-09-30 Source: ResearchSquare

    The novel coronavirus disease MESHD ( COVID-19 MESHD) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 MESHD infected MESHD patients may vary from gender to gender with a very high risk of death MESHD for seniors. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), testosterone (T), and dexamethasone (DEX) may change the interaction of coronavirus spike protein PROTEIN (CSP) with angiotensin converting enzyme-2 ( ACE2 HGNC). Data showed that E2 was more strongly to interact with the main protease PROTEIN of the coronavirus, while T had the lowest affinity for CSP. The binding energy of the CSP to ACE2 HGNC was increased in the presence of steroids; the greatest increase was observed by DEX and E2. The binding free energy of the CSP to ACE2 HGNC was the highest in the presence of E2 and DEX. Together, the interaction between CSP and ACE2 HGNC can be disrupted by E2 and to a greater extent by DEX, in part explaining the lower incidence of COVID-19 MESHD infection in women than men. The potential use of E2 and DEX to reduce coronavirus attachment MESHD to ACE2 HGNC in the early phase of the coronavirus invasion needs to be clinically investigated.

    Structural insights into decreased affinity of SARS-CoV-2 to ACE2 HGNC by steroids

    Authors: Alireza Mansouri; Rasoul Kowsar; Khaled Sadeghi; Akio Miyamoto

    doi:10.21203/rs.3.rs-83198/v1 Date: 2020-09-24 Source: ResearchSquare

    The novel coronavirus disease MESHD ( COVID-19 MESHD) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 MESHD infected MESHD patients may vary from gender to gender with a very high risk of death MESHD for seniors. Clearly, different levels of sex steroid hormones are found in both men and women. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), and testosterone (T) may change the interaction of coronavirus spike protein PROTEIN with angiotensin converting enzyme-2 ( ACE2 HGNC, which is the major SARS-CoV-2 cell entry receptor.) in the presence or absence of dexamethasone (DEX, the potential anti-inflammatory agents). Data showed that E2 was more strongly to interact with the main protease PROTEIN of the coronavirus, while T had the lowest affinity for coronavirus spike protein PROTEIN than E2 and P4. The binding energy of the spike protein PROTEIN to ACE2 HGNC was increased in the presence of five molecules of each steroid; the greatest increase was observed by DEX and E2. The binding free energy of the spike protein PROTEIN to ACE2 HGNC was the highest in the presence of both E2 and DEX HGNC molecules. Together, the interaction between spike protein PROTEIN and ACE2 HGNC can be disrupted by female sex steroid hormone E2 and to a greater extent by E2 and anti-inflammatory DEX, in part explaining the lower incidence of COVID-19 MESHD infection in women than men. The potential use of E2 and DEX HGNC to reduce coronavirus attachment MESHD to ACE2 HGNC in the early phase of the coronavirus invasion needs to be clinically investigated.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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