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Antioxidant Potential of Antiviral Drug Umifenovir
molecules Article Antioxidant Potential of Antiviral Drug Umifenovir Elena V. Proskurnina 1,*, Dmitry Yu. Izmailov 2, Madina M. Sozarukova 3, Tatiana A. Zhuravleva 2, Irina A. Leneva 4 and Artem A. Poromov 4 1 Research Centre for Medical Genetics, ul. Moskvorechye 1, Moscow 115522, Russia 2 Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky prospekt 27-1, Moscow 119234, Russia; [email protected] (D.Y.I.); [email protected] (T.A.Z.) 3 Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninsky prospekt 31, Moscow 119991, Russia; [email protected] 4 Department of Experimental Virology, Mechnikov Research Institute for Vaccines and Sera, Malyi Kazennyi pereulok 5a, Moscow 105064, Russia; [email protected] (I.A.L.); [email protected] (A.A.P.) * Correspondence: [email protected]; Tel.: +7-(499)-612-8193 Received: 21 February 2020; Accepted: 28 March 2020; Published: 30 March 2020 Abstract: Free radical reactions play an important role in biological functions of living systems. The balance between oxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Experimental works demonstrate the role of oxidative stress that is caused by influenza virus as well as the toxic effects of some antiviral drugs. Therefore, antiviral drugs should be characterized by its pro- and antioxidant activity, because it can affect its therapeutic efficiency. The aim of the study was to quantify the antioxidant capacity and propose the mechanism of the antioxidant effect of the antiviral drug Umifenovir (Arbidol®). The kinetic chemiluminescence with the 2,2’-azobis (2-amidinopropane) dihydrochloride + luminol system was used to quantify the antioxidant capacity of Umifenovir relative to the standard compound Trolox. -
Microorganisms-07-00521-V2.Pdf
microorganisms Review Are Community Acquired Respiratory Viral Infections an Underestimated Burden in Hematology Patients? Cristian-Marian Popescu 1,* , Aurora Livia Ursache 2, Gavriela Feketea 1 , Corina Bocsan 3, Laura Jimbu 1, Oana Mesaros 1, Michael Edwards 4,5, Hongwei Wang 6, Iulia Berceanu 7, Alexandra Neaga 1 and Mihnea Zdrenghea 1,7,* 1 Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes str., 400012 Cluj-Napoca, Romania; [email protected] (G.F.); [email protected] (L.J.); [email protected] (O.M.); [email protected] (A.N.) 2 The Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăs, tur 3-5, 400372 Cluj-Napoca, Romania; [email protected] 3 Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Ha¸tieganuUniversity of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; [email protected] 4 National Heart and Lung Institute, St Mary’s Campus, Imperial College London, London W2 1PG, UK; [email protected] 5 Medical Research Council (MRC) and Asthma UK Centre in Allergic Mechanisms of Asthma, London W2 1PG, UK 6 School of Medicine, Nanjing University, 22 Hankou Road, Nanjing 210093, China; [email protected] 7 Department of Hematology, Ion Chiricuta Oncology Institute, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania; [email protected] * Correspondence: [email protected] (C.-M.P.); [email protected] (M.Z.) Received: 8 October 2019; Accepted: 31 October 2019; Published: 2 November 2019 Abstract: Despite a plethora of studies demonstrating significant morbidity and mortality due to community-acquired respiratory viral (CRV) infections in intensively treated hematology patients, and despite the availability of evidence-based guidelines for the diagnosis and management of respiratory viral infections in this setting, there is no uniform inclusion of respiratory viral infection management in the clinical hematology routine. -
Emerging Role of Mucosal Vaccine in Preventing Infection with Avian Influenza a Viruses
viruses Review Emerging Role of Mucosal Vaccine in Preventing Infection with Avian Influenza A Viruses Tong Wang 1, Fanhua Wei 2 and Jinhua Liu 1,* 1 Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; [email protected] 2 College of Agriculture, Ningxia University, Yinchuan 750021, China; [email protected] * Correspondence: [email protected] Received: 22 July 2020; Accepted: 5 August 2020; Published: 7 August 2020 Abstract: Avian influenza A viruses (AIVs), as a zoonotic agent, dramatically impacts public health and the poultry industry. Although low pathogenic avian influenza virus (LPAIV) incidence and mortality are relatively low, the infected hosts can act as a virus carrier and provide a resource pool for reassortant influenza viruses. At present, vaccination is the most effective way to eradicate AIVs from commercial poultry. The inactivated vaccines can only stimulate humoral immunity, rather than cellular and mucosal immune responses, while failing to effectively inhibit the replication and spread of AIVs in the flock. In recent years, significant progresses have been made in the understanding of the mechanisms underlying the vaccine antigen activities at the mucosal surfaces and the development of safe and efficacious mucosal vaccines that mimic the natural infection route and cut off the AIVs infection route. Here, we discussed the current status and advancement on mucosal immunity, the means of establishing mucosal immunity, and finally a perspective for design of AIVs mucosal vaccines. Hopefully, this review will help to not only understand and predict AIVs infection characteristics in birds but also extrapolate them for distinction or applicability in mammals, including humans. -
Immunomodulators Under Evaluation for the Treatment of COVID-19
Immunomodulators Under Evaluation for the Treatment of COVID-19 Last Updated: August 4, 2021 Summary Recommendations See Therapeutic Management of Hospitalized Adults with COVID-19 for the COVID-19 Treatment Guidelines Panel’s (the Panel) recommendations on the use of the following immunomodulators for patients according to their disease severity: • Baricitinib with dexamethasone • Dexamethasone • Tocilizumab with dexamethasone Additional Recommendations There is insufficient evidence for the Panel to recommend either for or against the use of the following immunomodulators for the treatment of COVID-19: • Colchicine for nonhospitalized patients • Fluvoxamine • Granulocyte-macrophage colony-stimulating factor inhibitors for hospitalized patients • Inhaled budesonide • Interleukin (IL)-1 inhibitors (e.g., anakinra) • Interferon beta for the treatment of early (i.e., <7 days from symptom onset) mild to moderate COVID-19 • Sarilumab for patients who are within 24 hours of admission to the intensive care unit (ICU) and who require invasive mechanical ventilation, noninvasive ventilation, or high-flow oxygen (>0.4 FiO2/30 L/min of oxygen flow) The Panel recommends against the use of the following immunomodulators for the treatment of COVID-19, except in a clinical trial: • Baricitinib with tocilizumab (AIII) • Interferons (alfa or beta) for the treatment of severely or critically ill patients with COVID-19 (AIII) • Kinase inhibitors: • Bruton’s tyrosine kinase inhibitors (e.g., acalabrutinib, ibrutinib, zanubrutinib) (AIII) • Janus kinase inhibitors other than baricitinib (e.g., ruxolitinib, tofacitinib) (AIII) • Non-SARS-CoV-2-specific intravenous immunoglobulin (IVIG) (AIII). This recommendation should not preclude the use of IVIG when it is otherwise indicated for the treatment of complications that arise during the course of COVID-19. -
Current and Novel Approaches in Influenza Management
Review Current and Novel Approaches in Influenza Management Erasmus Kotey 1,2,3 , Deimante Lukosaityte 4,5, Osbourne Quaye 1,2 , William Ampofo 3 , Gordon Awandare 1,2 and Munir Iqbal 4,* 1 West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana; [email protected] (E.K.); [email protected] (O.Q.); [email protected] (G.A.) 2 Department of Biochemistry, Cell & Molecular Biology, University of Ghana, Legon, Accra P.O. Box LG 54, Ghana 3 Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra P.O. Box LG 581, Ghana; [email protected] 4 The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK; [email protected] 5 The University of Edinburgh, Edinburgh, Scotland EH25 9RG, UK * Correspondence: [email protected] Received: 20 May 2019; Accepted: 17 June 2019; Published: 18 June 2019 Abstract: Influenza is a disease that poses a significant health burden worldwide. Vaccination is the best way to prevent influenza virus infections. However, conventional vaccines are only effective for a short period of time due to the propensity of influenza viruses to undergo antigenic drift and antigenic shift. The efficacy of these vaccines is uncertain from year-to-year due to potential mismatch between the circulating viruses and vaccine strains, and mutations arising due to egg adaptation. Subsequently, the inability to store these vaccines long-term and vaccine shortages are challenges that need to be overcome. Conventional vaccines also have variable efficacies for certain populations, including the young, old, and immunocompromised. -
TITLE PAGE COVID-19 Treatment
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 26 March 2020 doi:10.20944/preprints202003.0378.v1 Peer-reviewed version available at International Journal of Antimicrobial Agents 2020; doi:10.1016/j.ijantimicag.2020.106080 TITLE PAGE COVID-19 Treatment: Close to a Cure? – A Rapid Review of Pharmacotherapies for the Novel Coronavirus 1. Yang Song, PharmD, BCPS Department of Pharmacy Services CHI Franciscan Health-St. Joseph Medical Center Tacoma, WA 98405 [email protected] 2. Min Zhang, PharmD, BCPS Department of Pharmacy Services Boston Medical Center Boston, MA 02118 3. Ling Yin, PharmD, PhD, BCPS, BCOP Department of Pharmacy Services AdventHealth Celebration Cancer Institute Celebration, FL 34747 4. Kunkun Wang, PharmD Department of Pharmacy Services Fairbanks Memorial Hospital Fairbanks, AK 99701 5. Yiyi Zhou, PharmD Department of Pharmacy Services Beijing United Family Hospital Beijing, China 100016 6. Mi Zhou, MM Department of Pharmacy Services Children’s Hospital of Soochow University Suzhou, China 215000 7. Yun Lu, PharmD, MS Associate Clinical Professor, University of Minnesota Department of Pharmacy Services Hennepin County Medical Center Minneapolis, MN 55415 1 © 2020 by the author(s). Distributed under a Creative Commons CC BY license. Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 26 March 2020 doi:10.20944/preprints202003.0378.v1 Peer-reviewed version available at International Journal of Antimicrobial Agents 2020; doi:10.1016/j.ijantimicag.2020.106080 Abstract Currently, there is no specific treatment for COVID-19 proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus- based and host-based therapeutics in order to combat SARS-CoV-2. -
Development and Effects of Influenza Antiviral Drugs
molecules Review Development and Effects of Influenza Antiviral Drugs Hang Yin, Ning Jiang, Wenhao Shi, Xiaojuan Chi, Sairu Liu, Ji-Long Chen and Song Wang * Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China; [email protected] (H.Y.); [email protected] (N.J.); [email protected] (W.S.); [email protected] (X.C.); [email protected] (S.L.); [email protected] (J.-L.C.) * Correspondence: [email protected] Abstract: Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal out- breaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treat- ment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some refer- ences for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development. -
High-Throughput Human Primary Cell-Based Airway Model for Evaluating Infuenza, Coronavirus, Or Other Respira- Tory Viruses in Vitro
www.nature.com/scientificreports OPEN High‑throughput human primary cell‑based airway model for evaluating infuenza, coronavirus, or other respiratory viruses in vitro A. L. Gard1, R. J. Luu1, C. R. Miller1, R. Maloney1, B. P. Cain1, E. E. Marr1, D. M. Burns1, R. Gaibler1, T. J. Mulhern1, C. A. Wong1, J. Alladina3, J. R. Coppeta1, P. Liu2, J. P. Wang2, H. Azizgolshani1, R. Fennell Fezzie1, J. L. Balestrini1, B. C. Isenberg1, B. D. Medof3, R. W. Finberg2 & J. T. Borenstein1* Infuenza and other respiratory viruses present a signifcant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as from COVID‑ 19. A barrier to the development of efective therapeutics is the absence of a robust and predictive preclinical model, with most studies relying on a combination of in vitro screening with immortalized cell lines and low‑throughput animal models. Here, we integrate human primary airway epithelial cells into a custom‑engineered 96‑device platform (PREDICT96‑ALI) in which tissues are cultured in an array of microchannel‑based culture chambers at an air–liquid interface, in a confguration compatible with high resolution in‑situ imaging and real‑time sensing. We apply this platform to infuenza A virus and coronavirus infections, evaluating viral infection kinetics and antiviral agent dosing across multiple strains and donor populations of human primary cells. Human coronaviruses HCoV‑NL63 and SARS‑CoV‑2 enter host cells via ACE2 and utilize the protease TMPRSS2 for spike protein priming, and we confrm their expression, demonstrate infection across a range of multiplicities of infection, and evaluate the efcacy of camostat mesylate, a known inhibitor of HCoV‑NL63 infection. -
Study Protocol
NCT03376321 Janssen Research & Development * Clinical Protocol A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pimodivir in Combination With the Standard-of-care Treatment in Adolescent, Adult, and Elderly Hospitalized Patients With Influenza A Infection Protocol 63623872FLZ3001; Phase 3 AMENDMENT 2 JNJ-63623872-ZCD Pimodivir *Janssen Research & Development is a global organization that operates through different legal entities in various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen Biologics, BV; Janssen-Cilag International NV; Janssen Pharmaceutica NV; Janssen, Inc; Janssen Sciences Ireland UC; or Janssen Research & Development, LLC. The term “sponsor” is used throughout the protocol to represent these various legal entities; the sponsor is identified on the Contact Information page that accompanies the protocol. This study will be conducted under US Food & Drug Administration IND regulations (21 CFR Part 312). EudraCT NUMBER: 2017-002156-84 Status: Approved Date: 11 June 2019 Prepared by: Janssen Research & Development, a division of Janssen Pharmaceutica NV EDMS number: EDMS-ERI-121941709, 10.0 GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory requirements. Confidentiality Statement The information in this document contains trade secrets and commercial information that are privileged or confidential and may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by them. -
Virus-Host Interactomics: New Insights and Opportunities for Antiviral Drug Discovery
de Chassey et al. Genome Medicine 2014, 6:115 http://genomemedicine.com/content/6/11/115 REVIEW Virus-host interactomics: new insights and opportunities for antiviral drug discovery Benoît de Chassey1, Laurène Meyniel-Schicklin1, Jacky Vonderscher1, Patrice André2,3,4 and Vincent Lotteau3,4* Abstract The current therapeutic arsenal against viral infections remains limited, with often poor efficacy and incomplete coverage, and appears inadequate to face the emergence of drug resistance. Our understanding of viral biology and pathophysiology and our ability to develop a more effective antiviral arsenal would greatly benefit from a more comprehensive picture of the events that lead to viral replication and associated symptoms. Towards this goal, the construction of virus-host interactomes is instrumental, mainly relying on the assumption that a viral infection at the cellular level can be viewed as a number of perturbations introduced into the host protein network when viral proteins make new connections and disrupt existing ones. Here, we review advances in interactomic approaches for viral infections, focusing on high-throughput screening (HTS) technologies and on the generation of high-quality datasets. We show how these are already beginning to offer intriguing perspectives in terms of virus-host cell biology and the control of cellular functions, and we conclude by offering a summary of the current situation regarding the potential development of host-oriented antiviral therapeutics. Introduction the virus life-cycle. These proteins -
Journal Pre-Proof
Journal Pre-proof Ongoing Clinical Trials for the Management of the COVID-19 Pandemic M.P. Lythgoe, P. Middleton PII: S0165-6147(20)30070-5 DOI: https://doi.org/10.1016/j.tips.2020.03.006 Reference: TIPS 1706 To appear in: Trends in Pharmacological Sciences Please cite this article as: M.P. Lythgoe and P. Middleton, Ongoing Clinical Trials for the Management of the COVID-19 Pandemic, Trends in Pharmacological Sciences (2020), https://doi.org/10.1016/j.tips.2020.03.006 This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier. Journal Pre-proof Ongoing Clinical Trials for the Management of the COVID-19 Pandemic *MP Lythgoe1 & *P Middleton2 1Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS, London, UK 2 Department of Metabolism, Digestion & Reproduction, Imperial College London, St Marys Hospital, Praed Street, W21NY, London UK *Equal contribution Corresponding Email: [email protected] Key words: Coronavirus, SARS-CoV-2, COVID-19, 2019-nCoV, pandemic ABSTRACT COVID-19 has rapidly developed into a worldwide pandemic causing a significant health and economic burden. -
SARS-Cov-2: Current Therapeutics Human and Veterinary Medicine
Iowa State University Capstones, Theses and Creative Components Dissertations Fall 2020 SARS-CoV-2: Current Therapeutics Human and Veterinary Medicine Andrea Garcia Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/creativecomponents Part of the Animal Diseases Commons, Other Veterinary Medicine Commons, Pharmacology Commons, Respiratory Tract Diseases Commons, and the Virus Diseases Commons Recommended Citation Garcia, Andrea, "SARS-CoV-2: Current Therapeutics Human and Veterinary Medicine" (2020). Creative Components. 643. https://lib.dr.iastate.edu/creativecomponents/643 This Creative Component is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Creative Components by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. SARS-CoV-2: Current Therapeutics Human and Veterinary Medicine Abstract The Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, was first reported in Wuhan City, China, in December 2019. Health and environmental risk factors are crucial in this current pandemic, yet it is essential to note that even though individuals of all ages are susceptive to this virus, there are risk factors associated with developing the severe disease. It is also eminent to establish the human-animal interaction by tackling important past pathogenic viruses such as SARS-CoV and MERS-CoV and its zoonotic links. In need of a clinically established management for this outbreak, approved drugs' therapeutic interventions could help treat this disease, targeting its replication. The need to resolve the current pandemic of COVID-19 epitomizes the need for a different approach, drug repurposing.