Antivirals articles within Nature Communications

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  • Article
    | Open Access

    Huang et al. show how plant Sw-5b NLR mimics the ABA receptor to activate ABA-dependent antiviral immunity via the PP2C-SnRK2 complex. They reveal that Sw-5b NLR induces ABA accumulation, upregulates ABA response genes, and triggers defense against viral infections by releasing SnRK2 from  PP2C inhibition.

    • Shen Huang
    • , Chunli Wang
    •  & Xiaorong Tao

  • Article
    | Open Access

    Effective antibodies targeting various respiratory syncytial virus (RSV) proteins are needed to address public health burden of RSV. Here the authors shows that in addition to the currently approved F-targeting monoclonal antibodies, anti-G cross-reactive monoclonal antibodies to RSV-A and RSV-B strains can provide cross-protection and prevent from RSV disease.

    • Youri Lee
    • , Laura Klenow
    •  & Surender Khurana

  • Article
    | Open Access

    Antiviral approaches against entire genera or families of viruses need to be constantly developed and innovated. Focusing on several distantly-related orthoflaviviruses, the authors develop a cell-based multiplex antiviral assay for high-throughput screening against multiple viruses at once.

    • Li-Hsin Li
    • , Winston Chiu
    •  & Kai Dallmeier

  • Article
    | Open Access

    There is limited data on how SARS-CoV-2 antivirals compare regarding efficacy and blocking transmission. Here, treating dwarf hamsters and ferrets with either molnupiravir or paxlovid the authors find comparable efficacy against severe COVID-19-like disease and complete block of transmission by molnupiravir.

    • Robert M. Cox
    • , Carolin M. Lieber
    •  & Richard K. Plemper

  • Article
    | Open Access

    Resistance to nirmatrelvir, an oral antiviral agent that targets SARS-CoV-2 and is clinically useful against infection with Omicron variants, is currently not well understood. In this study, the authors characterize mutant viruses with reduced sensitivity to nirmatrelvir in vitro and in vivo.

    • Maki Kiso
    • , Yuri Furusawa
    •  & Yoshihiro Kawaoka

  • Article
    | Open Access

    Ragonnet-Cronin et al scanned SARS-CoV-2 genomes from >12,000 treated patients, identifying nine treatment-emergent mutations that increased in frequency after treatment with antibodies. In the laboratory, synthetic viruses harbouring those mutations escaped the antibodies, suggesting the mutations are driven by immune evasion.

    • Manon Ragonnet-Cronin
    • , Rungtiwa Nutalai
    •  & Sakib Rokadiya

  • Article
    | Open Access

    Monkeypox virus is a pathogen with pandemic potential, encoding for its own RNA capping machinery. Here, the authors present crystal structures of its 2′-O-RNA methyltransferase VP39 in complex with sub-micromolar inhibitors and reveal similarities to SARS-CoV−2 nsp14 methyltransferase.

    • Jan Silhan
    • , Martin Klima
    •  & Evzen Boura

  • Article
    | Open Access

    Immunocompromised patients are vulnerable to respiratory viral infections. Here, the authors characterize cross-neutralizing antibodies to respiratory syncytial virus, human metapneumovirus, and human parainfluenza viruses and show effective protection in male hamsters.

    • Madelyn Cabán
    • , Justas V. Rodarte
    •  & Jim Boonyaratanakornkit

  • Article
    | Open Access

    The search for antivirals against SARS-CoV-2 continue due to the emergence of variants of concerns, able to escape the vaccinal humoral response. In this work, authors pre-clinically explore the potential of kinetin against SARS-CoV-2, which could be used alone or in combination with other antivirals.

    • Thiago Moreno L. Souza
    • , Vagner D. Pinho
    •  & Jaime A. Rabi

  • Article
    | Open Access

    Molnupiravir is an antiviral that forces lethal error catastrophe in SARS-CoV-2 RNAs. Here, the authors confirm the mechanism of action of molnupiravir in humans using samples obtained from the UK’s AGILE phase IIa clinical trial investigating the antiviral efficacy of the drug against SARS-CoV-2. No treatment-associated SARS-CoV-2 mutations were identified.

    • I’ah Donovan-Banfield
    • , Rebekah Penrice-Randal
    •  & Thomas Fletcher

  • Article
    | Open Access

    Repurposed antiviral drugs present as a valuable resource in the defence during outbreaks, with rigorous evaluation in large animal models keys for translation to clinical implementation. Here, the authors explore the antiviral activity of favipiravir against Zika virus and SARS-CoV-2 in cynomolgus macaques, in order to support future clinical investigations into this RNA polymerase inhibitor.

    • Romain Marlin
    • , Delphine Desjardins
    •  & Roger Le Grand

  • Article
    | Open Access

    Molnupiravir was the first orally available SARS-CoV-2 antiviral approved for outpatient use against SARS-CoV-2, but its efficacy against variants of concern, especially delta, was questioned. Here the authors evaluate molnupiravir against variant of concern in numerous models, including human airway epithelium organoids, ferrets and Roborovski dwarf hamsters.

    • Carolin M. Lieber
    • , Robert M. Cox
    •  & Richard K. Plemper

  • Article
    | Open Access

    Five New World mammarenaviruses (NWMs) enter cells via binding to human transferrin receptor 1 (hTfR1). Here, Hickerson et al. show that hTfR1 targeting antibodies partially protect hTfR1-transgenic mice from lethal NWM challenge via competition of anti-hTfR1 antibody and viral glycoprotein for hTfR1.

    • Brady T. Hickerson
    • , Tracy R. Daniels-Wells
    •  & Brian B. Gowen

  • Article
    | Open Access

    The V3-crown of the HIV-1 envelope protein largely elicits non-neutralizing antibodies. Here, the authors show that the V3-crown can be targeted by broadly neutralizing designed ankyrin repeat proteins recognizing two conformations one of which resembles CCR5- bound V3.

    • Nikolas Friedrich
    • , Emanuel Stiegeler
    •  & Alexandra Trkola

  • Article
    | Open Access

    Remdesivir is an approved antiviral treatment for COVID-19, but it needs to be administered intravenously. Here, Cox et al. show that GS-621763, a prodrug of remdesivir parent nucleoside GS-441524 has good oral bioavailability and inhibits SARS-CoV-2 and variants of concerns in ferrets.

    • Robert M. Cox
    • , Josef D. Wolf
    •  & Richard K. Plemper

  • Article
    | Open Access

    Sofosbuvir is a common therapy in hepatitis C virus infection, which targets the NS5B polymerase. Here, Smith et al. analyze the association between whole genome HCV polymorphisms and sofosbuvir treatment failure and identify three common polymorphisms present in non-targeted NS2 and NS3 proteins associated with reduced treatment response.

    • David A. Smith
    • , Carlota Fernandez-Antunez
    •  & M. Azim Ansari

  • Article
    | Open Access

    Remdesivir is under evaluation for treatment of COVID-19 in clinical trials. Here, the authors report results of remdesivir treatment in a patient with COVID-19 and the genetic antibody deficiency XLA. They show a temporally correlated clinical and virological response, suggesting that remdesivir can reduce SARS-CoV-2 replication in patients.

    • Matthew S. Buckland
    • , James B. Galloway
    •  & James E. D. Thaventhiran

  • Article
    | Open Access

    Here Zhao et al. report a promising broad-spectrum antiviral alkaline peptide—P9R—that is active against several respiratory, pH-dependent viruses, including Influenza and SARS-CoV-2. P9R interferes with virus internalization by binding to the virus and subsequent inhibition of endosomal acidification.

    • Hanjun Zhao
    • , Kelvin K. W. To
    •  & Kwok-Yung Yuen

  • Article
    | Open Access

    Herpes simplex virus establishes lifelong latency in ganglionic neurons, which are the source for recurrent infection. Here Aubert et al. report a promising antiviral therapy based on gene editing with adeno-associated virus-delivered meganucleases, which leads to a significant reduction in ganglionic HSV loads and HSV reactivation.

    • Martine Aubert
    • , Daniel E. Strongin
    •  & Keith R. Jerome

  • Article
    | Open Access

    Here, the authors show that sequential treatment with long-acting slow-effective release ART and AAV9- based delivery of CRISPR-Cas9 results in undetectable levels of virus and integrated DNA in a subset of humanized HIV-1 infected mice. This proof-of-concept study suggests that HIV-1 elimination is possible.

    • Prasanta K. Dash
    • , Rafal Kaminski
    •  & Howard E. Gendelman

  • Article
    | Open Access

    Viruses rely on host cell metabolism for replication, making these pathways potential therapeutic targets. Here, the authors show that AM580, a retinoid derivative and RAR-α agonist, affects replication of several RNA viruses by interfering with the activity of SREBP.

    • Shuofeng Yuan
    • , Hin Chu
    •  & Kwok-Yung Yuen

  • Article
    | Open Access

    The latent HIV-1 reservoir is the key obstacle for curing HIV-1 infection, but the timepoint at which the HIV-1 reservoir is established is currently unclear. Here, Whitney et al. show in non-human primates that the SIV reservoir in CD4+ T cells is seeded within the first 2 days after infection.

    • James B. Whitney
    • , So-Yon Lim
    •  & Dan H. Barouch

  • Article
    | Open Access

    Long-acting (LA) formulations of antiretroviral (ARV) drugs are an alternative approach to improve adherence for HIV treatment and prevention. Here the authors show a removable biodegradable ultra-LA-ARV drug system that effectively delivers drug, controls viremia and prevents infection in animal models of HIV infection.

    • Martina Kovarova
    • , S. Rahima Benhabbour
    •  & J. Victor Garcia

  • Article
    | Open Access

    Safety and efficacy remain important challenges for non-antiretroviral-based microbicides. Here, Derby et al. show that a Griffithsin-Carrageenan fast dissolving vaginal insert provides on-demand protection against SHIV infections in macaques, paving the way for the development of pre-exposure prophylaxis on-demand products.

    • Nina Derby
    • , Manjari Lal
    •  & Thomas M. Zydowsky

  • Article
    | Open Access

    A limited number of therapeutics is available to treat influenza A virus (IAV) infections. Here, the authors show that defective interfering genes, delivered with a dual-functional peptide that enables intracellular accumulation and prevents endosomal acidification, inhibit IAV replication in vitro and in vivo.

    • Hanjun Zhao
    • , Kelvin K. W. To
    •  & Kwok-Yung Yuen

  • Article
    | Open Access

    Tsg101 is a component of the host cellular ESCRT machinery and is required for HIV-1 replication. Here, the authors show that disruption of ubiquitin binding of the Tsg101 UEV domain through commonly used drugs arrests virus assembly, which might facilitate the development of potent HIV inhibitors.

    • Madeleine Strickland
    • , Lorna S. Ehrlich
    •  & Carol A. Carter

  • Article
    | Open Access

    Respiratory syncytial virus causes lung infections in children, immunocompromised adults, and in the elderly. Here the authors show that a chemical inhibitor to a viral fusion protein is effective in reducing viral titre and ameliorating infection in rodents and neonatal lambs.

    • Dirk Roymans
    • , Sarhad S Alnajjar
    •  & Anil Koul

  • Article
    | Open Access

    Reactivation of human cytomegalovirus in immunosuppressed transplant patients can cause severe complications. Here, Krishnaet al. show that a fusion toxin protein that specifically binds the viral surface protein US28 can be used to kill latently infected monocytes and their progenitor cells in vitro.

    • B. A. Krishna
    • , K. Spiess
    •  & J. H. Sinclair

  • Article
    | Open Access

    Human cytomegalovirus (CMV) poses a risk for immunosuppressed patients and newborns, with limited treatment options available. Here, Gardneret al. use a high-throughput approach and identify monoclonal antibodies that bind a highly conserved domain in the viral glycoprotein gH as potent inhibitors of CMV infection.

    • Thomas J. Gardner
    • , Kathryn R. Stein
    •  & Domenico Tortorella

  • Article
    | Open Access

    Cyclophilins play a key role in the life cycle of many viruses and represent important drug targets for broad-spectrum antiviral therapies. Here, the authors use fragment-based drug discovery to develop non-peptidic inhibitors of human cyclophilins with high activity against replication of a number of viral families.

    • Abdelhakim Ahmed-Belkacem
    • , Lionel Colliandre
    •  & Jean- François Guichou

  • Article
    | Open Access

    Charged phosphorylated metabolite such as nucleoside tri-phosphates exhibit poor membrane permeability due to their high polarity, limiting their utility as drugs or cellular probes. Here the authors develop a method to render nucleoside triphosphates cell permeable and allows their release by an enzyme-triggered mechanism.

    • Tristan Gollnest
    • , Thiago Dinis de Oliveira
    •  & Chris Meier

  • Article
    | Open Access

    In some HIV-1-infected individuals, viraemia remains undetectable after antiretroviral treatment, but which of these patients will experience viral rebound is difficult to predict. Here the authors show that T cell exhaustion markers before treatment are predictive of shorter time to viral rebound.

    • Jacob Hurst
    • , Matthias Hoffmann
    •  & John Frater

  • Article |

    HIV infection causes significant bone loss, which is worsened by antiretroviral therapy (ART). Here, the authors use a mouse model to show that T cell repopulation and/or immune reactivation after ART leads to complex inflammatory effects driving bone turnover and bone loss.

    • Ighovwerha Ofotokun
    • , Kehmia Titanji
    •  & M. Neale Weitzmann

  • Article
    | Open Access

    The cellular protein RIG-I detects viral RNA and activates another protein, MAVS, which then forms filaments and stimulates an antiviral pathway. Here, the authors identify different regions within MAVS involved in activating transcription factors IRF3 and NF-κB, and in MAVS self-inhibition.

    • Yuheng Shi
    • , Bofeng Yuan
    •  & Fajian Hou

  • Article
    | Open Access

    HIV-infected patients who maintain undetectable virus levels possess elevated plasma concentrations of IL-21. Here, Adoroet al. show that IL-21 inhibits early viral infection in humanized mice and suppresses HIV-1 replication in vitroby upregulating a microRNA via the regulatory protein STAT3.

    • Stanley Adoro
    • , Juan R. Cubillos-Ruiz
    •  & Laurie H. Glimcher

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