Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (1492)

ProteinN (428)

NSP5 (315)

ComplexRdRp (187)

ProteinE (102)


Filter

Genes
Diseases
SARS-CoV-2 Proteins
    displaying 41 - 50 records in total 23501
    records per page




    TMPRSS2 HGNC and RNA-dependent RNA polymerase PROTEIN are effective targets of therapeutic intervention for treatment of COVID-19 MESHD caused by SARS-CoV-2 variants (B.1.1.7 and B.1.351)

    Authors: Jihye Lee; JinAh Lee; Hyeon Ju Kim; Meehyun Ko; Youngmee Jee; Seungtaek Kim

    doi:10.1101/2021.04.06.438540 Date: 2021-04-08 Source: bioRxiv

    SARS-CoV-2 is a causative agent of COVID-19 pandemic MESHD and the development of therapeutic interventions is urgently needed. So far, monoclonal antibodies and drug repositioning are the main methods for drug development and this effort was partially successful. Since the beginning of COVID-19 pandemic MESHD, the emergence of SARS-CoV-2 variants has been reported in many parts of the world and the main concern is whether the current vaccines and therapeutics are still effective against these variant viruses. The viral entry and viral RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) are the main targets of current drug development, thus the inhibitory effects of TMPRSS2 HGNC and RdRp PROTEIN inhibitors were compared among the early SARS-CoV-2 isolate (lineage A) and the two recent variants (lineage B.1.1.7 and lineage B.1.351) identified in the UK and South Africa, respectively. Our in vitro analysis of viral replication showed that the drugs targeting TMPRSS2 HGNC and RdRp PROTEIN are equally effective against the two variants of concern.

    Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp13 Helicase

    Authors: Rupert Beale; Agustina P Bertolin; Annabel Borg; Berta Canal; John FX Diffley; Lucy S Drury; Ruth Harvey; Michael Howell; Saira Hussain; Svend Kjaer; John McCauley; Laura McCoy; Jennifer Milligan; Viktor Posse; Rachel Ulferts; Florian Weissmann; Mary Wu; Jingkun Zeng

    doi:10.1101/2021.04.07.438808 Date: 2021-04-08 Source: bioRxiv

    The coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there is a need for therapeutics. Repurposing existing drugs represents a promising and potentially rapid opportunity to find novel antivirals against SARS-CoV-2. The virus encodes at least nine enzymatic activities that are potential drug targets. Here we have expressed, purified and developed enzymatic assays for SARS-CoV-2 nsp13 helicase, a viral replication protein that is essential for the coronavirus life cycle. We screened a custom chemical library of over 5000 previously characterised pharmaceuticals for nsp13 inhibitors using a FRET-based high-throughput screening (HTS) approach. From this, we have identified FPA-124 and several suramin-related compounds as novel inhibitors of nsp13 helicase activity in vitro. We describe the efficacy of these drugs using assays we developed to monitor SARS-CoV-2 growth in Vero E6 cells.

    Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp3 HGNC Papain-like Protease PROTEIN

    Authors: Lee A Armstrong; Rupert Beale; Ganka Bineva-Todd; Berta Canal; John FX Diffley; Lucy S Drury; Michael Howell; Yogesh Kulathu; Karim Labib; Chew Theng Lim; Jennifer Milligan; Eiko Ozono; Kang Wei Tan; Florian Weissmann; Mary Wu; Theresa U Zeisner; Jingkun Zeng

    doi:10.1101/2021.04.07.438804 Date: 2021-04-08 Source: bioRxiv

    The COVID-19 pandemic MESHD has emerged as the biggest life-threatening disease of this century. Whilst vaccination should provide a long-term solution, this is pitted against the constant threat of mutations in the virus rendering the current vaccines less effective. Consequently, small molecule antiviral agents would be extremely useful to complement the vaccination program. The causative agent of COVID-19 MESHD is a novel coronavirus, SARS-CoV-2, which encodes at least nine enzymatic activities that all have drug targeting potential. The papain-like protease PROTEIN ( PLpro PROTEIN) contained in the nsp3 HGNC protein generates viral non-structural proteins from a polyprotein precursor, and cleaves ubiquitin and ISG protein conjugates. Here we describe the expression and purification of PLpro PROTEIN. We developed a protease assay that was used to screen a custom chemical library from which we identified Dihydrotanshinone I and Ro 08-2750 as compounds that inhibit PLpro PROTEIN in protease and isopeptidase assays and also inhibit viral replication in cell culture-based assays.

    Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp14/nsp10 Exoribonuclease PROTEIN

    Authors: Clovis Basier; Souradeep Basu; Rupert Beale; Agustina P Bertolin; Berta Canal; Joseph F Curran; Tom D Deegan; John FX Diffley; Lucy S Drury; Ryo Fujisawa; Michael Howell; Karim Labib; Allison W McClure; Jennifer Milligan; Rachel Ulferts; Florian Weissmann; Mary Wu; Jingkun Zeng

    doi:10.1101/2021.04.07.438812 Date: 2021-04-08 Source: bioRxiv

    SARS-CoV-2 is a coronavirus that emerged in 2019 and rapidly spread across the world causing a deadly pandemic with tremendous social and economic costs. Healthcare systems worldwide are under great pressure, and there is urgent need for effective antiviral treatments. The only currently approved antiviral treatment for COVID-19 MESHD is remdesivir, an inhibitor of viral genome replication. SARS-CoV-2 proliferation relies on the enzymatic activities of the non-structural proteins (nsp), which makes them interesting targets for the development of new antiviral treatments. With the aim to identify novel SARS-CoV-2 antivirals, we have purified the exoribonuclease PROTEIN/methyltransferase (nsp14) and its cofactor (nsp10) and developed biochemical assays compatible with high-throughput approaches to screen for exoribonuclease PROTEIN inhibitors. We have screened a library of over 5000 commercial compounds and identified patulin and aurintricarboxylic acid (ATA) as inhibitors of nsp14 exoribonuclease PROTEIN in vitro. We found that patulin and ATA inhibit replication of SARS-CoV-2 in a VERO E6 cell-culture model. These two new antiviral compounds will be valuable tools for further coronavirus research as well as potentially contributing to new therapeutic opportunities for COVID-19 MESHD.

    Synthetic repertoires derived from convalescent COVID-19 MESHD patients enable discovery of SARS-CoV-2 neutralizing antibodies and a novel quaternary binding modality

    Authors: Jimmy D Gollihar; Jason S McLellan; Daniel R Boutz; Jule Goike; Andrew Horton; Elizabeth C Gardner; Foteini Bartzoka; Niahshuang Wang; Kamyab Javanmardi; Andrew Herbert; Shawn Abbasi; Rebecca Renberg; Michael J Johanson; Jose A Cardona; Thomas Segall-Shapiro; Ling Zhou; Ruth H Nissly; Abhinay Gontu; Michelle Byrom; Andre C Maranhao; Anna M Battenhouse; Varun Gejji; Laura Soto-Sierra; Emma R Foster; Susan L Woodard; Zivko L Nikolov; Jason Lavinder; Will N Voss; Ankur Annapareddy; Gregory C Ippolito; Andrew D Ellington; Edward M Marcotte; Ilya J Finkelstein; Randall A Hughes; James M Musser; Suresh V Kuchipudi; Vivek Kapur; George Georgiou; John M Dye

    doi:10.1101/2021.04.07.438849 Date: 2021-04-08 Source: bioRxiv

    The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 MESHD patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (Kd,app = 68 pM) to the receptor binding domain (RBD) of the spike protein PROTEIN and robustly neutralizes the virus in vitro. This antibody likely binds all three RBDs of the trimeric spike protein PROTEIN with a single IgG. Importantly, N3-1 equivalently binds spike proteins PROTEIN from emerging SARS-CoV-2 variants of concern, neutralizes UK variant B.1.1.7, and binds SARS-CoV spike MESHD with nanomolar affinity. Taken together, the strategies described herein will prove broadly applicable in interrogating adaptive immunity and developing rapid response biological countermeasures to emerging pathogens.

    Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine (KCONVAC) in Healthy Adults: Two Randomized, Double-blind, and Placebo-controlled Phase 1/2 Clinical Trials

    Authors: Hong-Xing Pan; Jian-Kai Liu; Bao-Ying Huang; Gui-Fan Li; Xian-Yun Chang; Ya-Fei Liu; Wen-Ling Wang; Kai Chu; Jia-Lei Hu; Jing-Xin Li; Dan-Dan Zhu; Jing-Liang Wu; Xiao-Yu Xu; Li Zhang; Meng Wang; Wen-Jie Tan; Wei-Jin Huang; Feng-Cai Zhu

    doi:10.1101/2021.04.07.21253850 Date: 2021-04-08 Source: medRxiv

    Background The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine, KCONVAC, in healthy adults. Methods Two phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in Chinese healthy adults aged 18 through 59 years. The phase 1 trial was conducted in a manner of dosage escalation. The first 30 participants were randomized in a ratio of 4:1 to receive two doses of either KCONVAC at 5 g per dose or placebo on Day 0 and Day 14, and the second 30 participants were randomized to receive either KCONVAC at 10 g per dose or placebo following the same procedures. The participants in the phase 2 trial were randomized in a ratio of 2:2:1 to receive either KCONVAC at 5 g or 10 g per dose, or placebo on Day 0 and Day 14, or Day 0 and Day 28. In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following each vaccination. Antibody response and cellular response were assayed in the phase 1 trial. In the phase 2 trial, the primary immunogenicity endpoint was the seroconversion and titre of neutralization antibody, and the seroconversion of receptor binding domain (RBD)-IgG 28 days after the second dose. Findings In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-g vaccine (N=24), 10-g vaccine (N=24), or placebo (N=12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-g vaccine (N=100 for 0/14 or 0/28 regimens), 10-g vaccine (N=100 for each regimen), or placebo (N=50 for each regimen). In the phase 1 trial, 13 (54%), 11(46%), and 7 (58%) participants reported at least one adverse event (AE), of whom 10 (42%), 6 (25%), and 6 (50%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) participants reported at least one AE, of whom 13 (13%), 17 (17%), and 6 (12%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo at the regimen of Day 0/14, respectively. Similar results were observed in the three treatment groups of Day 0/28 regimen. All the AEs were grade 1 or 2 in intensity. No AE of grade 3 or more was reported. One SAE (foot fracture MESHD) was reported in the phase 1 trial. KCONVAC induced significant antibody response. 87.5% (21/24) to 100% (24/24) of participants in the phase 1 trial and 83.0% (83/100) to 100% (99/99) of participants in the phase 2 trial seroconverted for neutralising antibody to live virus, neutralising antibody to pseudovirus, and RBD-IgG after receiving two doses. Across the treatment groups in the two trials, the geometric mean titres (GMTs) of neutralising antibody to live virus ranged from 29.3 to 49.1 at Day 0/14 regimen and from 100.2 to 131.7 at Day 0/28 regimen, neutralising antibody to pseudovirus ranged from 69.4 to 118.7 at Day 0/14 regimen and from 153.6 to 276.6 at Day 0/28 regimen, and RBD-IgG ranged from 605.3 to 1169.8 at Day 0/14 regimen and from 1496.8 to 2485.5 at Day 0/28 regimen. RBD-IgG subtyping assay showed that a significant part of RBD-IgG was IgG1. The vaccine induced obvious T-cell response with 56.5% (13/23) and 62.5% (15/24) of participants in 5-g and 10-g vaccine groups showed positive interferon-{gamma HGNC} enzyme-linked immunospot responses 14 days after the second dose in the phase 1 trial, respectively. Interpretation KCONVAC is well tolerated and able to induce robust antibody response and cellular response in adults aged 18 to 59 years, which warrants further evaluation with this vaccine in the upcoming phase 3 efficacy trial. Funding Guandong Emergency Program for Prevention and Control of COVID-19 MESHD (2020A1111340002) and Shenzhen Key Research Project for Prevention and Control of COVID-19 MESHD.

    A repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 MESHD spike protein PROTEIN to ACE2

    Authors: Kaleb B Tsegay; Christiana M Adeyemi; Edward P Gniffke; John K Walker; Stephen E.P. Smith

    doi:10.1101/2021.04.08.439071 Date: 2021-04-08 Source: bioRxiv

    Repurposed drugs that block the interaction between the SARS-CoV-2 spike PROTEIN protein and its receptor ACE2 HGNC could offer a rapid route to novel COVID-19 MESHD treatments or prophylactics. Here, we screened 2701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike PROTEIN protein to recombinant human ACE2 HGNC. We identified 56 compounds that inhibited binding by <90%, measured the EC50 of binding inhibition, and computationally modeled the docking of the best inhibitors to both Spike and ACE2 HGNC. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike- ACE2 HGNC interaction as well as identifying several potential inhibitors that could serve as templates for future drug discovery efforts.

    Functional evaluation of proteolytic activation for the SARS-CoV-2 variant B.1.1.7: role of the P681H mutation

    Authors: Bailey Lubinski; Tiffany Tang; Susan Daniel; Javier A. Jaimes; Gary Whittaker

    doi:10.1101/2021.04.06.438731 Date: 2021-04-08 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the agent behind the current COVID-19 pandemic MESHD having emerged in Wuhan China in late 2019 from a yet to be determined animal reservoir. SARS-CoV-2 B.1.1.7, a variant identified in the UK in late 2020, contains a higher than typical level of point mutants across its genome, including P681H in the spike S1/S2 cleavage site. Here, we performed assays using fluorogenic peptides mimicking the S1/S2 sequence from Wuhan-Hu1 and B.1.1.7 and observed no definitive difference in furin cleavage between Wuhan-Hu1 and B.1.1.7 in vitro. We performed functional assays using pseudo-typed particles harboring SARS-CoV-2 spike PROTEIN proteins and observed no significant differences between Wuhan-Hu1, Wuhan-Hu1 P681H or B.1.1.7 spike-carrying pseudo-typed particles in VeroE6 or Vero-TMPRSS2 cells, despite the spikes containing P681H being more efficiently cleaved. Likewise, we or show no differences in cell-cell fusion assays using the spike P681H-expressing cells. Our findings suggest that while the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC).

    Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of nsp5 Main Protease PROTEIN

    Authors: Clovis Basier; Rupert Beale; Ganka Bineva-Todd; Berta Canal; Joseph F Curran; Tom D Deegan; John FX Diffley; Ryo Fujisawa; Michael Howell; Dhira Joshi; Karim Labib; Chew Theng Lim; Jennifer Milligan; Hema Nagaraj; George Papageorgiou; Christelle Soudy; Kang Wei Tan; Rachel Ulferts; Florian Weissmann; Mary Wu; Theresa U Zeisner

    doi:10.1101/2021.04.07.438806 Date: 2021-04-08 Source: bioRxiv

    The coronavirus 2019 ( COVID-19 MESHD) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), spread around the world with unprecedented health and socio-economic effects for the global population. While different vaccines are now being made available, very few antiviral drugs have been approved. The main viral protease (nsp5) of SARS-CoV-2 provides an excellent target for antivirals, due to its essential and conserved function in the viral replication cycle. We have expressed, purified and developed assays for nsp5 protease activity. We screened the nsp5 protease against a custom chemical library of over 5,000 characterised pharmaceuticals. We identified calpain inhibitor I and three different peptidyl fluoromethylketones (FMK) as inhibitors of nsp5 activity in vitro, with IC50 values in the low micromolar range. By altering the sequence of our peptidomimetic FMK inhibitors to better mimic the substrate sequence of nsp5, we generated an inhibitor with a subnanomolar IC50. Calpain inhibitor I inhibited viral infection in monkey-derived Vero E6 cells, with an EC50 in the low micromolar range. The most potent and commercially available peptidyl-FMK compound inhibited viral growth in Vero E6 cells to some extent, while our custom peptidyl FMK inhibitor offered a marked antiviral improvement.

    Polymersomes decorated with SARS-CoV-2 spike PROTEIN protein receptor binding domain elicit robust humoral and cellular immunity

    Authors: Lisa R Volpatti; Rachel P Wallace; Shijie Cao; Michal Raczy; Ruyi Wang; Laura T Gray; Aaron T Alpar; Priscilla S Briquez; Nikolaos Mitrousis; Tiffany M Marchell; Maria Stella Sasso; Mindy Nguyen; Aslan Mansurov; Erica Budina; Ani Solanki; Elyse A Watkins; Mathew R Schnorenberg; Andrew C Tremain; Joseph W Reda; Vlad Nicolaescu; Kevin Furlong; Steve Dvorkin; Shann S Yu; Balaji Manicassamy; James L LaBelle; Matthew V Tirrell; Glenn Randall; Marcin Kwissa; Melody Swartz; Jeffrey Hubbell

    doi:10.1101/2021.04.08.438884 Date: 2021-04-08 Source: bioRxiv

    A diverse portfolio of SARS-CoV-2 vaccine candidates is needed to combat the evolving COVID-19 pandemic MESHD. Here, we developed a subunit nanovaccine by conjugating SARS-CoV-2 Spike PROTEIN protein receptor binding domain (RBD) to the surface of oxidation-sensitive polymersomes. We evaluated the humoral and cellular responses of mice immunized with these surface-decorated polymersomes (RBDsurf) compared to RBD-encapsulated polymersomes (RBDencap) and unformulated RBD (RBDfree), using monophosphoryl lipid A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBDsurf elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBDsurf was the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBDsurf and RBDencap drove similarly robust CD4+ and CD8+ T cell responses that produced multiple Th1-type cytokines. We conclude that multivalent surface display of Spike RBD on polymersomes promotes a potent neutralizing antibody response to SARS-CoV-2, while both antigen formulations promote robust T cell immunity.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).
The web page can also be accessed via API.

Sources


Annotations

All
None
MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


Export subcorpus as...

This service is developed in the project nfdi4health task force covid-19 which is a part of nfdi4health.

nfdi4health is one of the funded consortia of the National Research Data Infrastructure programme of the DFG.