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antiviral agents

  • Open Access
    Off-Target <em>In Vitro</em> Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent
    Antiviral Agents
    Off-Target In Vitro Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent

    Remdesivir (RDV, GS-5734), the first FDA-approved antiviral for the treatment of COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. It is intracellularly metabolized into the active triphosphate form, which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases.

    Yili Xu, Ona Barauskas, Cynthia Kim, Darius Babusis, Eisuke Murakami, Dmytro Kornyeyev, Gary Lee, George Stepan, Michel Perron, Roy Bannister, Brian E. Schultz, Roman Sakowicz, Danielle Porter, Tomas Cihlar, Joy Y. Feng
  • Pharmacological Characterization of TP0591816, a Novel Macrocyclic Respiratory Syncytial Virus Fusion Inhibitor with Antiviral Activity against F Protein Mutants
    Antiviral Agents
    Pharmacological Characterization of TP0591816, a Novel Macrocyclic Respiratory Syncytial Virus Fusion Inhibitor with Antiviral Activity against F Protein Mutants

    Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in early childhood. However, no vaccines have yet been approved for prevention of RSV infection, and the treatment options are limited. Therefore, development of effective and safe anti-RSV drugs is needed. In this study, we evaluated the antiviral activity and mechanism of action of a novel macrocyclic anti-RSV compound, TP0591816. TP0591816...

    Ippei Yoshida, Kaho Arikawa, Yusuke Honma, Shoko Inatani, Mitsukane Yoshinaga, Hiroyuki Sugiyama
  • Free
    Repurposing Nucleoside Analogs for Human Coronaviruses
    Antiviral Agents
    Repurposing Nucleoside Analogs for Human Coronaviruses

    Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or CoV-2). Some reports claimed certain nucleoside analogs to be active against CoV-2 and thus needed confirmation. Here, we evaluated a panel of compounds and identified novel nucleoside analogs with antiviral activity against CoV-2 and HCoV-OC43 while ruling out others. Of significance, sofosbuvir demonstrated...

    Keivan Zandi, Franck Amblard, Katie Musall, Jessica Downs-Bowen, Ruby Kleinbard, Adrian Oo, Dongdong Cao, Bo Liang, Olivia O. Russell, Tamara McBrayer, Leda Bassit, Baek Kim, Raymond F. Schinazi
  • Sulfonated Nanomaterials with Broad-Spectrum Antiviral Activity Extending beyond Heparan Sulfate-Dependent Viruses
    Antiviral Agents
    Sulfonated Nanomaterials with Broad-Spectrum Antiviral Activity Extending beyond Heparan Sulfate-Dependent Viruses

    Viral infections are among the main causes of death worldwide, and we lack antivirals for the majority of viruses. Heparin-like sulfated or sulfonated compounds have been known for decades for their ability to prevent infection by heparan sulfate proteoglycan (HSPG)-dependent viruses but only in a reversible way. We have previously shown that gold nanoparticles and β-cyclodextrins coated with mercapto-undecane sulfonic acid (MUS)...

    Valeria Cagno, Matteo Gasbarri, Chiara Medaglia, Diana Gomes, Sophie Clement, Francesco Stellacci, Caroline Tapparel
  • Free
    Favipiravir and the Need for Early Ambulatory Treatment of SARS-CoV-2 Infection (COVID-19)
    Commentary
    Favipiravir and the Need for Early Ambulatory Treatment of SARS-CoV-2 Infection (COVID-19)

    It is becoming increasingly clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like most human viral infections, will require multiple drugs in combination to treat COVID-19 illness. In this issue of the Journal, Doi and colleagues describe successful treatment of patients with early COVID-19 with favipiravir, an oral polymerase inhibitor, to rapidly and substantially clear SARS-CoV-2 from nasal secretions...

    Peter A. McCullough
  • Population Pharmacokinetics of Intravenous and Oral Acyclovir and Oral Valacyclovir in Pediatric Population To Optimize Dosing Regimens
    Pharmacology
    Population Pharmacokinetics of Intravenous and Oral Acyclovir and Oral Valacyclovir in Pediatric Population To Optimize Dosing Regimens

    Acyclovir is an antiviral currently used for the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. This study aimed to characterize the pharmacokinetics (PK) of acyclovir and its oral prodrug valacyclovir to optimize dosing in children. Children receiving acyclovir or valacyclovir were included in this study. PK were described using nonlinear mixed-effect modeling. Dosing simulations...

    S. Abdalla, C. Briand, M. Oualha, M. Bendavid, A. Béranger, S. Benaboud, J.-M. Tréluyer, Y. Zheng, C. Capito, Z. Demir, F. Foissac, S. Winter, I. Gana, S. Boujaafar, N. Bouazza, D. Hirt
  • Open Access
    Preclinical Profile and Characterization of the Hepatitis B Virus Core Protein Inhibitor ABI-H0731
    Antiviral Agents
    Preclinical Profile and Characterization of the Hepatitis B Virus Core Protein Inhibitor ABI-H0731

    ABI-H0731, a first-generation hepatitis B virus (HBV) core protein inhibitor, has demonstrated effective antiviral activity in chronic hepatitis B (CHB) patients in a phase 1b clinical trial and is currently being further evaluated in phase 2 clinical trials. Here, we report the preclinical profile of ABI-H0731. In in vitro cell culture systems (HepG2-derived cell lines HepAD38 and HepG2-NTCP and primary human hepatocytes [PHHs...

    Qi Huang, Dawei Cai, Ran Yan, Lichun Li, Yuhua Zong, Lida Guo, Alexandre Mercier, Yi Zhou, Ariel Tang, Kirk Henne, Richard Colonno
  • The Clinically Approved Antifungal Drug Posaconazole Inhibits Human Cytomegalovirus Replication
    Antiviral Agents
    The Clinically Approved Antifungal Drug Posaconazole Inhibits Human Cytomegalovirus Replication

    Posaconazole (PCZ) is a clinically approved drug used predominantly for prophylaxis and salvage therapy of fungal infections. Here, we report its previously undescribed anti-human cytomegalovirus (HCMV) activity. By using antiviral assays, we demonstrated that PCZ, along with other azolic antifungals, has a broad anti-HCMV activity, being active against different strains, including low-passage-number clinical isolates and strains...

    Beatrice Mercorelli, Anna Luganini, Marta Celegato, Giorgio Palù, Giorgio Gribaudo, Galina I. Lepesheva, Arianna Loregian
  • Open Access
    Targeting the Respiratory Syncytial Virus N<sup>0</sup>-P Complex with Constrained α-Helical Peptides in Cells and Mice
    Antiviral Agents
    Targeting the Respiratory Syncytial Virus N0-P Complex with Constrained α-Helical Peptides in Cells and Mice

    Respiratory syncytial virus (RSV) is the main cause of severe respiratory infection in young children worldwide, and no therapies have been approved for the treatment of RSV infection. Data from recent clinical trials of fusion or L polymerase inhibitors for the treatment of RSV-infected patients revealed the emergence of escape mutants, highlighting the need for the discovery of inhibitors with novel mechanisms of action. Here we...

    Marie Galloux, Nadège Gsponer, Vanessa Gaillard, Brice Fenner, Thibaut Larcher, Marthe Vilotte, Julie Rivière, Charles-Adrien Richard, Jean-François Eléouët, Ronan Le Goffic, Joelle Mettier, Origène Nyanguile
  • <em>In Vitro</em> and <em>In Vivo</em> Activity, Tolerability, and Mechanism of Action of BX795 as an Antiviral against Herpes Simplex Virus 2 Genital Infection
    Antiviral Agents
    In Vitro and In Vivo Activity, Tolerability, and Mechanism of Action of BX795 as an Antiviral against Herpes Simplex Virus 2 Genital Infection

    Herpes simplex virus type 2 (HSV-2) causes recurrent lesions in the anogenital area that may be transmitted through sexual encounters. Nucleoside analogs, such as acyclovir (ACV), are currently prescribed clinically to curb this infection. However, in some cases, reduced efficacy has been observed due to the emergence of resistance against these drugs. In our previous study, we reported the discovery of a novel anti-HSV-1 small molecule...

    James Hopkins, Tejabhiram Yadavalli, Rahul Suryawanshi, Farreh Qatanani, Ipsita Volety, Ram Koganti, Aqsa Iqbal, Deepak Shukla

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