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antiviral agents

  • Open Access
    Antiviral Drug Discovery To Address the COVID-19 Pandemic
    Commentary | Therapeutics and Prevention
    Antiviral Drug Discovery To Address the COVID-19 Pandemic

    The magnitude of the morbidity and mortality inflicted upon the global population in less than 1 year has driven the inescapable conclusion that the discovery and development of effective antiviral drugs for COVID-19 are urgent and should be prioritized. The antiviral drug discovery programs that emerged for HIV and hepatitis C virus have enabled technology and expertise to accelerate this process for SARS-CoV-2. The description of...

    Douglas D. Richman
  • Open Access
    GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection
    Research Article | Molecular Biology and Physiology
    GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection

    Targeting the main protease (Mpro) of SARS-CoV-2, we identified two indole-chloropyridinyl-ester derivatives, GRL-0820 and GRL-0920, active against SARS-CoV-2, employing RNA-qPCR and immunocytochemistry and show that the two compounds exerted potent activity against SARS-CoV-2. While GRL-0820 and remdesivir blocked SARS-CoV-2 infection, viral breakthrough occurred as examined with immunocytochemistry. In contrast, GRL-0920...

    Shin-ichiro Hattori, Nobuyo Higshi-Kuwata, Jakka Raghavaiah, Debananda Das, Haydar Bulut, David A. Davis, Yuki Takamatsu, Kouki Matsuda, Nobutoki Takamune, Naoki Kishimoto, Tadashi Okamura, Shogo Misumi, Robert Yarchoan, Kenji Maeda, Arun K. Ghosh, Hiroaki Mitsuya
  • Open Access
    Hijacking the Fusion Complex of Human Parainfluenza Virus as an Antiviral Strategy
    Research Article | Therapeutics and Prevention
    Hijacking the Fusion Complex of Human Parainfluenza Virus as an Antiviral Strategy

    Paramyxoviruses, including human parainfluenza virus type 3, are internalized into host cells by fusion between viral and target cell membranes. The receptor binding protein, hemagglutinin-neuraminidase (HN), upon binding to its cell receptor, triggers conformational changes in the fusion protein (F). This action of HN activates F to reach its fusion-competent state. Using small molecules that interact with HN, we can induce the...

    T. C. Marcink, E. Yariv, K. Rybkina, V. Más, F. T. Bovier, A. des Georges, A. L. Greninger, C. A. Alabi, M. Porotto, N. Ben-Tal, A. Moscona
  • Open Access
    Strong <em>In Vivo</em> Inhibition of HIV-1 Replication by Nullbasic, a Tat Mutant
    Research Article | Therapeutics and Prevention
    Strong In Vivo Inhibition of HIV-1 Replication by Nullbasic, a Tat Mutant

    HIV-1 infection is effectively controlled by antiviral therapy that inhibits virus replication and reduces viral loads below detectable levels in patients. However, therapy interruption leads to viral rebound due to latently infected cells, which serve as a source of continued viral infection. Interest in strategies leading to a functional cure for HIV-1 infection by long-term or permanent viral suppression is growing. Here, we show...

    Hongping Jin, Yifan Sun, Dongsheng Li, Min-Hsuan Lin, Mary Lor, Lina Rustanti, David Harrich
  • Open Access
    Stable Occupancy of the Crimean-Congo Hemorrhagic Fever Virus-Encoded Deubiquitinase Blocks Viral Infection
    Editor's Pick Research Article | Host-Microbe Biology
    Stable Occupancy of the Crimean-Congo Hemorrhagic Fever Virus-Encoded Deubiquitinase Blocks Viral Infection

    Crimean-Congo hemorrhagic fever virus is an important human pathogen with a wide global distribution for which no therapeutic interventions are available. CCHFV encodes a cysteine protease belonging to the ovarian tumor (OTU) family which is involved in host immune suppression. Here we demonstrate that artificially prolonged binding of the OTU to a substrate inhibits virus infection. This provides novel insights into CCHFV OTU function...

    Florine E. M. Scholte, Brian L. Hua, Jessica R. Spengler, John V. Dzimianski, JoAnn D. Coleman-McCray, Stephen R. Welch, Laura K. McMullan, Stuart T. Nichol, Scott D. Pegan, Christina F. Spiropoulou, Éric Bergeron
  • Open Access
    Early Steps in Herpes Simplex Virus Infection Blocked by a Proteasome Inhibitor
    Research Article | Therapeutics and Prevention
    Early Steps in Herpes Simplex Virus Infection Blocked by a Proteasome Inhibitor

    Viruses usurp host cell functions to advance their replicative agenda. HSV relies on cellular proteasome activity for successful infection. Proteasome inhibitors, such as MG132, block HSV infection at multiple stages of the infectious cycle. Targeting host cell processes for antiviral intervention is an unconventional approach that might limit antiviral resistance. Here we demonstrated that the proteasome inhibitor bortezomib, which is...

    Seth M. Schneider, Suzanne M. Pritchard, George A. Wudiri, Chasity E. Trammell, Anthony V. Nicola
  • Open Access
    Research Article
    Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease

    Coronaviruses (CoVs) cause severe human infections, but there are no approved antivirals to treat these infections. Development of nucleoside-based therapeutics for CoV infections has been hampered by the presence of a proofreading exoribonuclease. Here, we expand the known efficacy of the nucleotide prodrug remdesivir (GS-5734) to include a group β-2a CoV. Further, GS-5734 potently inhibits CoVs with intact proofreading. Following...

    Maria L. Agostini, Erica L. Andres, Amy C. Sims, Rachel L. Graham, Timothy P. Sheahan, Xiaotao Lu, Everett Clinton Smith, James Brett Case, Joy Y. Feng, Robert Jordan, Adrian S. Ray, Tomas Cihlar, Dustin Siegel, Richard L. Mackman, Michael O. Clarke, Ralph S. Baric, Mark R. Denison
  • Open Access
    Research Article
    Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral Pathogens

    A significant proportion of the world’s population is infected with herpes simplex virus. Primary infection and subsequent recurrent reactivation can result in diseases ranging from mild lesions to severe ocular or neurological damage. Herpesviruses are subject to epigenetic regulation that modulates viral gene expression, lytic replication, and latency-reactivation cycles. Thus, epigenetic pharmaceuticals have the potential to alter...

    Jesse H. Arbuckle, Paul J. Gardina, David N. Gordon, Heather D. Hickman, Jonathan W. Yewdell, Theodore C. Pierson, Timothy G. Myers, Thomas M. Kristie
  • Open Access
    Commentary
    Can an FDA-Approved Alzheimer’s Drug Be Repurposed for Alleviating Neuronal Symptoms of Zika Virus?
    Devika Sirohi, Richard J. Kuhn
  • Open Access
    Research Article
    A Novel Agonist of the TRIF Pathway Induces a Cellular State Refractory to Replication of Zika, Chikungunya, and Dengue Viruses
    Kara M. Pryke, Jinu Abraham, Tina M. Sali, Bryan J. Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason Baird, Michael Gough, Marita Chakhtoura, Elias K. Haddad, Ilsa T. Kirby, Aaron Nilsen, Daniel N. Streblow, Alec J. Hirsch, Jessica L. Smith, Victor R. DeFilippis

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