Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

NSP3 (1)

NSP1 (1)

NSP5 (1)


SARS-CoV-2 Proteins
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    A genome-wide CRISPR/Cas9 knock-out screen identifies the DEAD box RNA helicase DDX42 HGNC as a broad antiviral inhibitor

    Authors: Boris Bonaventure; Antoine Rebendenne; Francisco Garcia de Gracia; Marine Tauziet; Joe McKellar; Ana Luiza Chaves Valadão; Valérie Courgnaud; Eric Bernard; Laurence Briant; Nathalie Gros; Wassila Djilli; Mary Arnaud-Arnould; Hugues Parrinello; Stéphanie Rialle; Olivier Moncorgé; Caroline Goujon; Ronit Rosenfeld; Ron Alcalay; Eran Zahavy; Haim Levy; Itai Glinert; Amir Ben-Shmuel; Tomer Israely; Sharon Melamed; Boaz Politi; Hagit Achdout; Shmuel Yitzhaky; Chanoch Kronman; Tamar Sabo; Alina Renz; Muhammad Naveez; Zsolt Bocskei; Daniela Bornigen; Liam Fergusson; Marta Conti; Marius Rameil; Vanessa Nakonecnij; Jakob Vanhoefer; Leonard Schmiester; Muying Wang; Emily E Ackerman; Jason E Shoemaker; Jeremy Zucker; Kristie L Oxford; Jeremy Teuton; Ebru Kocakaya; Gokce Yagmur Summak; Kristina Hanspers; Martina Kutmon; Susan Coort; Lars Eijssen; Friederike Ehrhart; Rex D. A. B.; Denise Slenter; Marvin Martens; Robin Haw; Bijay Jassal; Lisa Matthews; Marija Orlic-Milacic; Andrea Senff-Ribeiro; Karen Rothfels; Veronica Shamovsky; Ralf Stephan; Cristoffer Sevilla; Thawfeek Mohamed Varusai; Jean-Marie Ravel; Vera Ortseifen; Silvia Marchesi; Piotr Gawron; Ewa Smula; Laurent Heirendt; Venkata Satagopam; Guanming Wu; Anders Riutta; Martin Golebiewski; Stuart Owen; Carole Goble; Xiaoming Hu; Rupert Overall; Dieter Maier; Angela Bauch; John A Bachman; Benjamin M Gyori; Carlos Vega; Valentin Groues; Miguel Vazquez; Pablo Porras; Luana Licata; Marta Iannuccelli; Francesca Sacco; Denes Turei; Augustin Luna; Ozgun Babur; Sylvain Soliman; Alberto Valdeolivas; Marina Esteban-Medina; Maria Pena-Chilet; Tomas Helikar; Bhanwar Lal Puniya; Anastasia Nesterova; Anton Yuryev; Anita de Waard; Dezso Modos; Agatha Treveil; Marton Laszlo Olbei; Bertrand De Meulder; Aurelien Naldi; Aurelien Dugourd; Laurence Calzone; Chris Sander; Emek Demir; Tamas Korcsmaros; Tom C Freeman; Franck Auge; Jacques S Beckmann; Jan Hasenauer; Olaf Wolkenhauer; Egon Willighagen; Alexander R Pico; Chris Evelo; Lincoln D Stein; Henning Hermjakob; Julio Saez-Rodriguez; Joaquin Dopazo; Alfonso Valencia; Hiroaki Kitano; Emmanuel Barillot; Charles Auffray; Rudi Balling; Reinhard Schneider; - the COVID-19 Disease Map Community

    doi:10.1101/2020.10.28.359356 Date: 2020-10-28 Source: bioRxiv

    Genome-wide CRISPR/Cas9 knock-out genetic screens are powerful approaches to unravel new regulators of viral infections MESHD. With the aim of identifying new cellular inhibitors of HIV-1, we have developed a strategy in which we took advantage of the ability of type 1 interferon (IFN) to potently inhibit HIV-1 infection MESHD, in order to create a cellular environment hostile to viral replication. This approach led to the identification of the DEAD-box RNA helicase DDX42 HGNC as an intrinsic inhibitor of HIV-1. Depletion of endogenous DDX42 HGNC using siRNA or CRISPR/Cas9 knock-out increased HIV-1 infection MESHD, both in model cell lines and in physiological targets of HIV-1, primary CD4+ T cells and monocyte-derived macrophages (MDMs), and irrespectively of the IFN treatment. Similarly, the overexpression of a dominant-negative mutant of DDX42 HGNC positively impacted HIV-1 infection MESHD, whereas wild-type DDX42 HGNC overexpression potently inhibited HIV-1 infection MESHD. The positive impact of endogenous DDX42 HGNC depletion on HIV-1 infection MESHD was directly correlated to an increase in viral DNA accumulation. Interestingly, proximity ligation assays showed that DDX42 HGNC, which can be mainly found in the nucleus but is also present in the cytoplasm, was in the close vicinity of HIV-1 Capsid during infection of primary monocyte-derived macrophages. Moreover, we show that DDX42 HGNC is also able to substantially decrease infection with other retroviruses and retrotransposition of long interspersed elements-1 (LINE-1). Finally, we reveal that DDX42 HGNC potently inhibits other pathogenic viruses, including Chikungunya virus MESHD and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

    Isolation and characterization of high affinity and highly stable anti-Chikungunya virus antibodies using ALTHEA Gold Libraries™

    Authors: Martha Pedraza-Escalona; Omar Guzmán-Bringas; Ivan Arrieta-Oliva; Keyla Gómez-Castellano; Juana Salinas-Trujano; Jesus Torres-Flores; Juan Muñoz-Herrera; Rosa Camacho-Sandoval; Paola Contreras-Pineda; Rommel Chacón-Salinas; Sonia Mayra Pérez-Tapia; Juan Carlos Almagro

    doi:10.21203/ Date: 2020-06-12 Source: ResearchSquare

    Background: More than three million infections were attributed to Chikungunya virus (CHIKV) in the 2014-2016 outbreak in Mexico, Central and South America, with over 500 deaths directly or indirectly related to this viral disease. CHIKV MESHD outbreaks are recurrent and no vaccine nor approved therapeutics exist to prevent or treat CHIKV infection MESHD. Reliable and robust diagnostic methods are thus critical to control future CHIKV outbreaks. Direct CHIKV detection in serum samples via highly specific and high affinity anti-CHIKV antibodies has shown to be an early and effective clinical diagnosis. Methods:  To isolate highly specific and high affinity anti-CHIKV, Chikungunya virions were isolated from serum of a patient in Veracruz, México. After purification and characterization via electron microscopy, SDS-PAGE and binding to well-characterized anti-CHIKV antibodies, UV-inactivated particles were utilized as selector in a solid-phase panning in combination with ALTHEA Gold Libraries™, as source of antibodies. The screening was based on ELISA and Next-Generation Sequencing. Results: The CHIKV isolate showed the typical morphology of the virus. Protein bands in the SDS-PAGE were consistent with the size of CHIKV capsid proteins. UV-inactivated CHIKV particles bound tightly the control antibodies. The lead antibodies here obtained, on the other hand, showed high expression yield, > 95% monomeric content after a single-step Protein A purification, and importantly, had a thermal stability above 75oC. Most of the antibodies recognized linear epitopes on E2, including the highest affinity antibody called C7. A sandwich ELISA implemented with C7 and a potent neutralizing antibody isolated elsewhere, also specific for E2 but recognizing a discontinuous epitope, showed a dynamic range of 0.2 – 40.0 mg/mL of UV-inactivated CHIKV purified preparation. The number of CHIKV particles estimated based on the concentration of E2 in the extract suggested that the assay could detect clinically meaningful amounts of CHIKV in serum.Conclusions: The newly discovered antibodies offer valuable tools for characterization of CHIKV isolates and development of robust diagnostic tools for CHIKV infection MESHD surveillance. Therefore, the strategy here followed using whole viral particles and ALTHEA Gold Libraries™ as universal source of antibodies could expedite the discovery and development of antibodies for detection and control of emergent and quickly spreading viral outbreaks.

    A Proposed Randomized, Double Blind, Placebo Controlled Study Evaluating Doxycycline for the Prevention of COVID-19 MESHD Infection and Disease In Healthcare Workers with Ongoing High Risk Exposure to COVID-19 MESHD

    Authors: Paul A Yates; Ashton M Leone; Elias Reichel

    doi:10.1101/2020.05.11.20098525 Date: 2020-05-18 Source: medRxiv

    This paper proposes both a rationale and potential study design for evaluation of low dose doxycycline (20mg BID HGNC) for the prevention of COVID-19 MESHD infection in exposed health care workers. More generally, it provides a potential study design blueprint to other investigators for any interventional COVID-19 MESHD study looking to evaluate interventions for prevention or treatment of COVID-19 MESHD infection. This specific study described is a randomized, double blind, placebo controlled study to evaluate the efficacy and safety of doxycycline for the prevention of COVID-19 MESHD infection and disease in healthcare workers with ongoing high risk exposure to COVID-19 MESHD. This study would consist of a 50-day Treatment Period (Day 0-Day 50), followed by an End of Study Visit, approximately 30 days after completion of study drug dosing. Initially, for approximately the first 4 to 6 weeks, an initial open-label arm would be enrolled with up to 1938 subjects who will be assigned to take 20mg doxycycline BID HGNC. In the double blind, placebo controlled arms approximately 3,692 participants would be randomized to either doxycycline or placebo for 50 days. Doxycycline is a rational candidate drug to be evaluated for repurposing against SARS-CoV-2. Doxycycline is a generally safe tetracycline derivative that has been available for decades, most commonly dosed at 100mg BID HGNC to treat bacterial infections MESHD. However, in addition to its anti-microbial properties, doxycycline (and more generally tetracycline derivatives) may have a role as an effective anti-viral agent and as an anti-inflammatory drug. Early studies indicate potential efficacy of minocycline against respiratory syncytial virus (RSV) [12], and doxycycline against Dengue and Chikungunya infection MESHD[9, 10]. In addition, doxycycline is known or proposed to target several pathways that regulate viral replication. [13, 14, 15]. Doxycycline is a particularly attractive candidate as a COVID-19 MESHD prophylactic given it has been used in clinical practice for decades and maintains an excellent safety profile as demonstrated in multiple clinical studies. Any effective prophylaxis for COVID-19 MESHD should be able to demonstrate high efficacy at preventing infection and/or lowering severity of disease. Equally important, it should demonstrate this efficacy at dosing levels that are highly unlikely to precipitate any untoward severe side effects. Doxycycline has been selected based on its ability to: 1) inhibit metalloproteinases (MMPs), implicated in initial viral entry into the cell as well as in acute respiratory distress syndrome MESHD ( ARDS MESHD) associated with severe COVID-19 MESHD infection [13, 16]; 2) potential to inhibit Papain-like proteinase ( PLpro PROTEIN) responsible for proteolytic cleavage of the replicase polyprotein to release non-structural proteins 1 PROTEIN, 2 & 3 (Nsp1, Nsp2 and Nsp3) all essential for viral replication. [19]; 3) potential to inhibit 3C-like main protease PROTEIN ( 3CLpro PROTEIN) or Nsp5 which is cleaved from the polyproteins causes further cleavage of Nsp4-16 and mediates maturation of Nsps which is essential in the virus lifecycle. [19]; 4) act as an ionophore help transport Zinc intracellularly, increasing cellular concentrations of Zinc to inhibit viral replication. [6, 15]; 5) inhibit Nf-kB which may lower inflammatory response to COVID-19 MESHD infection, and lower risk of viral entry due to decreasing DPP4 cell surface receptor. [20, 21]; 6) inhibits (specifically low-dose doxycycline) expression of CD147/EMMPRIN that may be necessary for SARS-CoV-2 entry into T lymphocytes [22, 23].

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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