DOCSLIB.ORG

Uses and Administration Adverse Effects Profile Profile Profile Uses

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Uses and Administration Adverse Effects Profile Profile Profile Uses Penciclovir/Raltegravir 1009 disorders. Peptide T has also been tried in the treatment of clinical studies to date the FDA considers that it may rarely References. psoriasis. cause anaphylaxis or serious skin reactions. As with other 1. Hirayama C, et al. Propagermairlum: a nonsped.fic immune modulator for chronic hepatitis B. J Gastroenterol 2003; 38: 525-32. neuraminidase inhibitors, neurologic and behavioral symptoms have been infrequently reported. For further Peramivir (USAN, r/NN} information on neurological and other adverse effects �r.��.��!�<?.�� .......................................................................... .. associated with neuraminidase inhibitors, see under ProprielaryPreparations (details are given in Volume B) Oseltamivir, p. I 007 .2. Patients with known or suspected renal insufficiency Single-ingredient Preparations.Jp n: Serocion. should have a baseline creatinine clearance measurement before taking peramivir. Dosage adjustments may be necessary in patients with renal impairment. �.��P.�.��.!�<>.��... ........................................................................ (details are given in Volume B) Uses and Administration ProprielaryPreparations Single-ingredient Preparations.Jp n: Rapiacta. Peramivir is a neuraminidase inhibitor that is given intravenously; it is being evaluated in phase 3 clinical studies for the treatment of influenza (see p. 960.2). Although it has not yet been approved for marketing, the FDA has authorised the emergency use of peramivir in the USA to treat certain adult and paediatric patients with suspected or laboratory-confirmed pandemic (HINI) 2009 influenza, or infection due to nonsubtypable influenza A virus suspected to be 2009 HINI based on community epidemiology. The recommended dose for patients from 18 years of age is 600 mg given intravenously over 30 minutes once daily for s to 10 days. Dose adjustments are needed in patients with renal impairment, see below. For details of doses in children, see below. Profile Administration in children. Peramivir may be given to Pleconaril is an antiviral with activity against a range of children in the treatment of pandemic (HINI) 2009 influ­ picomaviruses. It has been investigated for the oral enza, similarly to adults (see above). Doses may be given treatment of viral meningitis and encephalitis, upper intravenously over 60 minutes once daily for S to 10 days Uses and Administration respiratory-tract viral infections, and other enteroviral according to age as follows: Raltegravir is an inhibitor of HIV integrase, an enzyme infections. However, there have been concerns over birth to 30 days old: 6 mg/kg essential for insertion of viral DNA into the host genome, • efficacy, viral resistance, and interactions with oral 31 to 90 days old: 8 mg/kg and thus for replication. It is used with other antiretrovirals • contraceptives. Development of an intranasal formulation 91 to 180 days old: I 0 mg/kg for treatment of HIV infection and AIDS (p. 957.2) and is • for the common cold has also been investigated. • 18I days old to S years of age: 12 mg/kg licensed for use in both treatment-naive and treatment­ 6 to 17 years of age: I 0 mg/kg References. experienced patients. • l. The maximum daily dose is 600 mg. For details of dose Nowak·Wegrzyn A. et al. Successful treatment of enterovirus infection It is given orally as the potassium salt but doses are with the use of pleconaril in 2 infants with severe combined adjustments in children with renal impairment, see below. immunodefidency. Clin Infect Dis 2001; 32: El3-E l4. expressed in terms of the base; 434 mg of raltegravir 2. Rotbart HA, Webster Treatment of potentially life-threatening AD. potassium is equivalent to about 400 mg of raltegravir. The Administration in renol impairment. Intravenous doses of enterovirus infections with pleconaril. Clin Infect Dis 2001; 32: 228-35. usual dose is the equivalent of 400 mg of raltegravir twice 3. Aradottir E, et al. Severe neonatal enteroviral hepatitis treated with peramivir should be reduced in patients with renal impair­ daily, with or without food. For details of doses in children pleconaril. Pediatr Infect Dis J 2001; 20: 457-9. ment, according to creatinine clearance (CC): 4. Starlin R, et al. Acute flaccid paralysis syndrome associated with and adolescents, see below. Adultsfrom years of age. echovirus 19, managed with pleconaril and intravenous immunoglobu­ Doses of raltegravir may need to be amended when given lin. Clin Infect 2001; 33: 730-2. • CC 31 to18 49 mL/minute: ISO mg daily Dis with rifampicin: a dose of 800 mg twice daily has been CC 10 to 30mL/minute: IOOmg daily 5. Hayden FG, et al. Oral pleconaril treatment of picornavirus-associated suggested. • viral respiratory illness in adults: efficacy and tolerability in phase II CC less than IOmL/minute: IOOmg on day I, then ISmg • clinical trials. Antivir Ther 2002; 7: 53--65. References. daily thereafter 6. Abzug MJ, et al. Double blind placebo-controlled trial of pleconaril in 1. Iwamoto M, et al. Safety, tolerability, and pharmacokinetics of infants with enterovirus meningitis. Pediatr Infect Dis J 2003; 22: 335-41. • Intermittent haemodialysis: IOOmg on day I, and 2 raltegravir after single and multiple doses in healthy subjects. Clin hours after the end of each dialysis session 7. Hayden FG, et al. Efficacy and safety of oral pleconaril for treatment of Pharmacol Ther 2008; 83: 293-9. colds due to picornaviruses in adults: results of 2 double-blind, 2. Croxtall JD, et al. Raltegravir. Druos 2008; 68: 131-8. Infantsand children. 36: randomized, placebo-controlled trials. Clin Infect Dis 200?; 1523-32. 3. Croxtall JD, Kearn SJ. Raltegravir: a review of its use in the management • CC 31 to 49 mL/minute per !.73m2: 8. Webster AD. Pleconaril-an advance in the treatment of enteroviral of infection in treatment-experienced patients. Drugs 2009; 69: infection in immuno-compromised patients. J Clin Virol 2005; 32: 1-6. mv • l.S mg/kg daily in those from birth to 30 days old 1059-75. 2 mg/kg daily in those from 31 to 90 days old 9. Desmond RA, et al. Enteroviral meningitis: natural history and outcome 4. Hicks C, Gulick RM. Raltegravir: the first HIV type 1 integrase inhibitor. • of pleconaril therapy. Antimicrob Agents Chemother 2006; 50: 2409-14. 48: 2.5 mg/kg daily in those from 91 to 180 days old Clin Infect Dis 2009; 931-9. • 5. Lennox JL, et al. Safety and efficacy of raltegravir-based versus • 3 mg/kg daily in those from 181 days old to S years of efavirenz-based combination therapy in treatment-naive piltients with age HIV-1 infection: a multicentre, double-blind randomised controlled trial. C12U Lancet 2009; 374: 796-806. Correction. ibid.; 786. • 2.S mg/kg daily in those from 6 to I7 years of age 6. Croxtall JD, Scott Raltegravir: in treatment-naive patients with HIV- CC 10 to 30mL/minute per !.73m2: IJ. • 1 infection. Druos 2010; 70: 631-42. ' • I mg/kg daily in those from birth to 30 days old 7. Steigbigel RT, et al. BENCHMRK Study Teams. Long-term efficacy and • 1.3mg/kg daily in those from 31 to 90 days old safety of raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant mv infection: week • 1.6mg/kg dally in those from 91 to 180 days old Profile 96 results of the BENCHMRK 1 and 2 phase trials. Clin Infect Dis 2010; I.9 mg/kg daily in those from 181 days old to S years m • Poly I.poly CI2U is a synthetic mismatched polymer of 50: 605-12. of age double-stranded RNA with antiviral and immunomodula­ 8. Ramkumar K, Neamati N. Raltegravir: the evidence of its therapeutic 1.6 mg/kg daily in those from 6 to 17 years of age value in HIV-1 infection. Core Evid2010 ; 4: 131-47. • tory activity (see also Poly I. Poly C, p. 2S94. 1). It is under 2 9. Ski est DJ, et al. Similar efficacy of raltegravir when used with or without • CC less than IOmL/minute per !.73m : investigation in the treatment of HIV infection, and also in I mg/kg on day I, then O.IS mg/kg daily in those from a protease inhibitor in treatment-experienced patients. HN Clin Trials • renal cell carcinoma, chronic fatigue syndrome, invasive 2011; 12: 131-40. birth to 30 days old melanoma, and hepatitis B and C. 10. Brainard DM, et al. Clinical pharmacology profile of raltegravir, an IDV-1 51: • 1.3 mg/kg on day I, then 0.2 mg/kg dally in those integrase strand transfer inhibitor. J Clin Pharmaco/ 2011; 1376-1402. from 31 to 90 days old 11. Rokas KEE, et al. Role of raltegravir in HIV-1 management. Ann Pharmacother 2012; 46: 578-89. • 1.6 mg/kg on day I, then 0.2S mg/kg daily in those �r.��.�?.!�<?.�� ............................................................................ from 91 to 180 days old ProprielaryPreparations (details are given in Volume B) 1.9mg/kg on day I, then 0.3mg/kg daily in those Administration in children. For the treatment of HIV • USA: from I81 days to S years of age Single-ingredient Preparations. Ampligen. infection in children from 2 years of age and adolescents raltegravir is given with other antiretroviral drugs. In the • 1.6 mg/kg on day I, then 0.2S mg/kg daily in those from 6 to 17 years of age USA, oral film-coated or chewable tablets are available; the two formulations are not interchangeable as the chewable • For children on intermittent haemodialysis, the following doses, based on age and weight, are given on tablet has a higher bioavailability compared with the rum­ day I, and then 2 hours after each dialysis session: coated tablets. Doses are based on body-weight. In children from 2 years (and weighing at least 10 kg) to • I mg/kg for those from birth to 30 days old less than 12 years of age, the following dose recommenda­ • I.3 mg/kg for those from 31 to 90 days old lions are made for chewable tablets: • 1.6mg/kg for those from 91 to 180 days old I 0 to less than 14 kg: 7 S mg twice daily • I.9 mg/kg for those from 181 days to S years of age • 14 to less than 20 kg: 100 mg twice daily • 1.6 mg/kg for those from 6 to 17 years of age • Profile • 20 to less than 28 kg: ISO mg twice daily AdverseEffects • 28 to less than 40 kg: 200 mg twice daily Propagermanium is an immunomodulator that has been • at least 40 kg: 300 mg twice daily (maximum dose) Safety and efficacy data for peramivir are limited.
Load more

Recommended publications
  • Development of Antiviral Agents for Enteroviruses
    Journal of Antimicrobial Chemotherapy (2008) 62, 1169–1173 doi:10.1093/jac/dkn424 Advance Access publication 18 October 2008 Development of antiviral agents for enteroviruses Tzu-Chun Chen1–3, Kuo-Feng Weng1,2, Shih-Cheng Chang1,2, Jing-Yi Lin1,2, Peng-Nien Huang1,2 and Shin-Ru Shih1,2,4,5* 1Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan; 2Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan; 3Institute Downloaded from https://academic.oup.com/jac/article/62/6/1169/774341 by guest on 26 September 2021 of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan; 4Clinical Virology Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Chunan, Taiwan Enteroviruses (EVs) are common human pathogens that are associated with numerous disease symptoms in many organ systems of the body. Although EV infections commonly cause mild or non- symptomatic illness, some of them are associated with severe diseases such as CNS complications. The current absence of effective vaccines for most viral infection and no available antiviral drugs for the treatment of EVs highlight the urgency and significance of developing antiviral agents. Several key steps in the viral life cycle are potential targets for blocking viral replication. This article reviews recent studies of antiviral developments for EVs based on various molecular targets that interrupt viral attach- ment, viral translation, polyprotein processing and RNA replication. Keywords: capsid proteins, viral proteases, viral RNA replication, 50 untranslated region Introduction EVs such as echovirus 6, 9 and 30 and CVB5 were the most common causes of aseptic meningitis in children.4 EV70 and Enteroviruses (EVs) are a common cause of infections in CVA24 were associated with acute haemorrhagic conjunctivitis.4 humans, especially children.
    [Show full text]
  • The Evolution of Pleconaril: Modified O-Alkyl Linker Analogs Have
    molecules Communication The Evolution of Pleconaril: Modified O-Alkyl Linker Analogs Have Biological Activity towards Coxsackievirus B3 Nancy 1, 2, 1 3 Alexandrina Volobueva y, Anna Egorova y, Anastasia Galochkina , Sean Ekins , Vladimir Zarubaev 1 and Vadim Makarov 2,* 1 Saint-Petersburg Pasteur Institute, Mira str., 14, 197101 Saint Petersburg, Russia; [email protected] (A.V.); [email protected] (A.G.); [email protected] (V.Z.) 2 Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky prospect, 33, build. 2, 119071 Moscow, Russia; [email protected] 3 Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, NC 27606, USA; [email protected] * Correspondence: [email protected] These authors contributed equally to this work. y Received: 10 February 2020; Accepted: 13 March 2020; Published: 16 March 2020 Abstract: Coxsackieviruses type B are one of the most common causes of mild upper respiratory and gastrointestinal illnesses. At the time of writing, there are no approved drugs for effective antiviral treatment for Coxsackieviruses type B. We used the core-structure of pleconaril, a well-known antienteroviral drug candidate, for the synthesis of novel compounds with O-propyl linker modifications. Some original compounds with 4 different linker patterns, such as sulfur atom, ester, amide, and piperazine, were synthesized according to five synthetic schemes. The cytotoxicity and bioactivity of 14 target compounds towards Coxsackievirus B3 Nancy were examined. Based on the results, the values of 50% cytotoxic dose (CC50), 50% virus-inhibiting dose (IC50), and selectivity index (SI) were calculated for each compound. Several of the novel synthesized derivatives exhibited a strong anti-CVB3 activity (SI > 20 to > 200).
    [Show full text]
  • Update on Viral Infections Involving the Central Nervous System in Pediatric Patients
    children Review Update on Viral Infections Involving the Central Nervous System in Pediatric Patients Giovanni Autore 1, Luca Bernardi 1, Serafina Perrone 2 and Susanna Esposito 1,* 1 Pediatric Clinic, Pietro Barilla Children’s Hospital, Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy; [email protected] (G.A.); [email protected] (L.B.) 2 Neonatology Unit, Pietro Barilla Children’s Hospital, Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy; serafi[email protected] * Correspondence: [email protected]; Tel.: +39-0521-704790 Abstract: Infections of the central nervous system (CNS) are mainly caused by viruses, and these infections can be life-threatening in pediatric patients. Although the prognosis of CNS infections is often favorable, mortality and long-term sequelae can occur. The aims of this narrative review were to describe the specific microbiological and clinical features of the most frequent pathogens and to provide an update on the diagnostic approaches and treatment strategies for viral CNS infections in children. A literature analysis showed that the most common pathogens worldwide are enteroviruses, arboviruses, parechoviruses, and herpesviruses, with variable prevalence rates in different countries. Lumbar puncture (LP) should be performed as soon as possible when CNS infection is suspected, and cerebrospinal fluid (CSF) samples should always be sent for polymerase chain reaction (PCR) analysis. Due to the lack of specific therapies, the management of viral CNS infections is mainly based on supportive care, and empiric treatment against herpes simplex virus (HSV) infection should be started as soon as possible.
    [Show full text]
  • Review Antivirals Against Enteroviruses: a Critical Review from a Public-Health Perspective
    Antiviral Therapy 2015; 20:121–130 (doi: 10.3851/IMP2939) Review Antivirals against enteroviruses: a critical review from a public-health perspective Kimberley SM Benschop1*, Harrie GAM van der Avoort1, Erwin Duizer1, Marion PG Koopmans1,2 1Centre for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment, Bilthoven, the Netherlands 2Department of Viroscience, Erasmus Medical Centre, Rotterdam, the Netherlands *Corresponding author e-mail: [email protected] The enteroviruses (EVs) of the Picornaviridae family are potential emergence of drug-resistant strains and their the most common viral pathogens known. Most EV infec- impact on EV transmission and endemic circulation. We tions are mild and self-limiting but manifestations can include non-picornavirus antivirals that inhibit EV rep- be severe in children and immunodeficient individuals. lication, for example, ribavirin, a treatment for infection Antiviral development is actively pursued to benefit these with HCV, and amantadine, a treatment for influenza A. high-risk patients and, given the alarming problem of They may have spurred resistance emergence in HCV or antimicrobial drug resistance, antiviral drug resistance influenza A patients who are unknowingly coinfected is a public-health concern. Picornavirus antivirals can be with EV. The public-health challenge is always to find a used off-label or as part of outbreak control measures. balance between individual benefit and the long-term They may be used in the final stages of poliovirus eradi- health of the larger population. cation and to mitigate EV-A71 outbreaks. We review the Introduction Enteroviruses (EVs) are among the most common of the PV eradication process and as part of outbreak circulating viruses known.
    [Show full text]
  • Appendices: V Ervolgonderzoek Medicatieveiligheid
    APPENDICES: V ERVOLGONDERZOEK MEDICATIEVEILIGHEID Dit is een bijlage bij het rapport Vervolgonderzoek Medicatieveiligheid en is opgesteld voor het Ministerie van VWS vanuit een samenwerkingsverband tussen het Erasmus MC (Rotterdam), NIVEL (Utrecht), Radboud UMC (Nijmegen) en PHARMO (Utrecht) Januari 2017 Versie 1.0 1 Appendices Hoofstuk 2: Onderzoek naar de mate van opvolging van HARM-Wrestling aanbevelingen (2009-2014) 2 Appendix 1 Appendix 1: Technische omzetting van HARM-Wrestling aanbevelingen naar indicatoren Algemene specificaties Tabel A1a. Bepaling van medicatiegebruik. Geneesmiddel of ATC-code geneesmiddelen groep Antidepressiva N06A Laag gedoseerd ASA B01AC06, B01AC08, B01AC30, N02BA15 (dosering 100mg) of N02BA01 (dosering 80mg) Benzodiazepinen N05CF, N05CD, N05BA of N05CC Beta-blokkers C07 Bisfosfonaten M05BA, M05BB, of M05XX Calcineurine remmers L04AA05 of L04AD01 Carbamazepine N03AF01 Corticosteroiden H02AB Co-trimoxazol J01EE01 Coxibs M01AH Diabetesmedicatie A10 Digoxine C01AA05 Glibenclamide A10BB01 of A10BD02 of A10BD04 H2RA A02BA Itraconazol J02AC02 Kaliumsparende diuretica C03DA, C03DB, of C03EA Kaliumverliezende diuretica C03A, C03B, C03E, C07B, C07CB03, C09BA, C09DA, C09XA52, C03C of C09DX01 Ketoconazol J02AB02 Niet-selectieve NSAID’s N02BA01, N02BA15, N02BA11, N02BA51, N02BA65 of M01A met uitzondering van M01AH, M01AX05, M01AX12, M01AX21, M01AX24, M01AX25 en M01AX26 Laxantia A06A, A02AA02, A02AA03, A02AA04, A06AC, A06AA, of A06AG Lisdiuretica C03C Macroliden J01FA of A02BD04 VKA B01AA Opioïden N02AA met uitzondering van N02AA55, N02AA59 en N02AA79, N02AB, N02AC, N02AD, N02AG, N02AE of N07BC01 Pentamidine P01CX01 PPI’s A02BC of M01AE52 RAS-remmers C09 Sotalol C07AA07 Spironolacton C03DA01 SSRI's N06AB, N06AX21 of N06AX16 Sulonylureumderivaten A10BB, A10BD02 of A10BD04 Thiazidediuretica C03A, C03B, C03EA, C07B, C09BA, C09DA, C09XA52, C09DX01 of C07CB03 TAR B01AC04, B01AC06, B01AC08, B01AC22, B01AC30, N02BA15 (dosering 100mg) of N02BA01 (dosering 80mg) Thienopyridine derivaten B01AC04, B01AC22 of B01AC30 3 Appendix 1 Tabel A1b.
    [Show full text]
  • Surveillance of Antimicrobial Consumption in Europe 2013-2014 SURVEILLANCE REPORT
    SURVEILLANCE REPORT SURVEILLANCE REPORT Surveillance of antimicrobial consumption in Europe in Europe consumption of antimicrobial Surveillance Surveillance of antimicrobial consumption in Europe 2013-2014 2012 www.ecdc.europa.eu ECDC SURVEILLANCE REPORT Surveillance of antimicrobial consumption in Europe 2013–2014 This report of the European Centre for Disease Prevention and Control (ECDC) was coordinated by Klaus Weist. Contributing authors Klaus Weist, Arno Muller, Ana Hoxha, Vera Vlahović-Palčevski, Christelle Elias, Dominique Monnet and Ole Heuer. Data analysis: Klaus Weist, Arno Muller and Ana Hoxha. Acknowledgements The authors would like to thank the ESAC-Net Disease Network Coordination Committee members (Marcel Bruch, Philippe Cavalié, Herman Goossens, Jenny Hellman, Susan Hopkins, Stephanie Natsch, Anna Olczak-Pienkowska, Ajay Oza, Arjana Tambić Andrasevic, Peter Zarb) and observers (Jane Robertson, Arno Muller, Mike Sharland, Theo Verheij) for providing valuable comments and scientific advice during the production of the report. All ESAC-Net participants and National Coordinators are acknowledged for providing data and valuable comments on this report. The authors also acknowledge Gaetan Guyodo, Catalin Albu and Anna Renau-Rosell for managing the data and providing technical support to the participating countries. Suggested citation: European Centre for Disease Prevention and Control. Surveillance of antimicrobial consumption in Europe, 2013‒2014. Stockholm: ECDC; 2018. Stockholm, May 2018 ISBN 978-92-9498-187-5 ISSN 2315-0955
    [Show full text]
  • Emerging Drug List PLECONARIL
    Emerging Drug List PLECONARIL NO. 15 SEPTEMBER 2001 Generic (Trade Name): Pleconaril (PicovirTM) Manufacturer: ViroPharma Indication: For the treatment of viral respiratory infections (common cold) in adults. Current Regulatory ViroPharma announced on July 31, 2001 that they had submitted a new drug application Status: with the U.S. FDA for the clearance of pleconaril for the treatment of viral respiratory infection (common cold) in adults. ViroPharma has not filed a submission with Health Canada but will be discussing that possibility with Aventis in the near future. Globally, pleconaril has not been approved by any regulatory body. Pleconaril is currently in Phase II clinical trials for treatment of the common cold in children, as well as treatment of otitis media and asthma. Pleconaril has also been studied for the treatment of viral meningitis and other potentially life-threatening enteovirus infections. Description: Pleconaril is an antipicornavirus agent. Picornaviruses include enteroviruses and rhinoviruses (the two types of viruses that account for the majority of human viral infections). Pleconaril integrates within a hydrophobic pocket inside the virion. This results in the viral capsid becoming compressed and rigid. This effect interrupts the viral infection cycle by preventing the virus from attaching to cells and/or releasing viral RNA from the capsid. For the treatment of the common cold in adults, the dose of pleconaril has ranged from 300 to 400 mg (orally) three times daily for five to seven days. Pleconaril should be given with a fat containing meal to enhance absorption. Current Existing No products are indicated for the treatment of the common cold.
    [Show full text]
  • Antiviral Activity Exerted by Natural Products Against Human Viruses
    viruses Review Antiviral Activity Exerted by Natural Products against Human Viruses Maria Musarra-Pizzo 1, Rosamaria Pennisi 1,2 , Ichrak Ben-Amor 1,3, Giuseppina Mandalari 1,* and Maria Teresa Sciortino 1,* 1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale SS. Annunziata, 98168 Messina, Italy; [email protected] (M.M.-P.); [email protected] (R.P.); [email protected] (I.B.-A.) 2 Shenzhen International Institute for Biomedical Research, 1301 Guanguang Rd. 3F Building 1-B, Silver Star Hi-Tech Park Longhua District, Shenzhen 518116, China 3 Unit of Biotechnology and Pathologies, Higher Institute of Biotechnology of Sfax, University of Sfax, Sfax 3029, Tunisia * Correspondence: [email protected] (G.M.); [email protected] (M.T.S.); Tel.: +39-090-6767-5217 (G.M. & M.T.S.) Abstract: Viral infections are responsible for several chronic and acute diseases in both humans and animals. Despite the incredible progress in human medicine, several viral diseases, such as acquired immunodeficiency syndrome, respiratory syndromes, and hepatitis, are still associated with high morbidity and mortality rates in humans. Natural products from plants or other organisms are a rich source of structurally novel chemical compounds including antivirals. Indeed, in traditional medicine, many pathological conditions have been treated using plant-derived medicines. Thus, the identification of novel alternative antiviral agents is of critical importance. In this review, we summarize novel phytochemicals with antiviral activity against human viruses and their potential application in treating or preventing viral disease. Citation: Musarra-Pizzo, M.; Pennisi, R.; Ben-Amor, I.; Mandalari, G.; Keywords: viral infections; natural bioactive compounds; novel antiviral drugs; drug resistance Sciortino, M.T.
    [Show full text]
  • In Vitro Characterisation of a Pleconaril/Pirodavir-Like Compound with Potent Activity Against Rhinoviruses
    Lacroix et al. Virology Journal (2015) 12:106 DOI 10.1186/s12985-015-0330-4 SHORT REPORT Open Access In vitro characterisation of a pleconaril/ pirodavir-like compound with potent activity against rhinoviruses Céline Lacroix1, Samuela Laconi2, Fabrizio Angius2, Antonio Coluccia3, Romano Silvestri3, Raffaello Pompei2, Johan Neyts1* and Pieter Leyssen1 Abstract Background: Rhinovirus infections do not only cause common colds, but may also trigger severe exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Even though rhinoviruses have been the focus of extensive drug development efforts in the past, an anti-rhinoviral drug still has to make it to the market. In the past, the viral capsid protein VP1 has been shown to be an important target for the development of antiviral molecules. Furthermore, many different chemical scaffolds appear to possess the properties that are required to inhibit virus replication by this mechanism of action. I-6602, an analogue of the rhinovirus inhibitor pirodavir, was previously identified as a potent inhibitor of rhinovirus infection. Here, we describe the antiviral activity of its analogue ca603, a molecule with a modified linker structure, and corroborate its mechanism of action as a capsid binder. Findings: The molecule ca603 shows antiviral activity against a panel of rhino-and enteroviruses. Cross-resistance is observed against viruses with mutations that render them resistant to the inhibitory effect of the capsid binder pleconaril and thermostability assays demonstrate that the compound binds and stabilizes the viral capsid. Binding of the molecule to the VP1 protein is corroborated by in silico modeling. Conclusions: It is confirmed that ca603 inhibits rhinovirus replication by interaction with the VP1 protein and, by this, allows to further expand the chemical diversity of capsid-binding molecules.
    [Show full text]
  • A Computational Approach to Aid Clinicians in Selecting Anti-Viral
    www.nature.com/scientificreports OPEN A computational approach to aid clinicians in selecting anti‑viral drugs for COVID‑19 trials Aanchal Mongia1, Sanjay Kr. Saha2, Emilie Chouzenoux3* & Angshul Majumdar1* The year 2020 witnessed a heavy death toll due to COVID‑19, calling for a global emergency. The continuous ongoing research and clinical trials paved the way for vaccines. But, the vaccine efcacy in the long run is still questionable due to the mutating coronavirus, which makes drug re‑positioning a reasonable alternative. COVID‑19 has hence fast‑paced drug re‑positioning for the treatment of COVID‑19 and its symptoms. This work builds computational models using matrix completion techniques to predict drug‑virus association for drug re‑positioning. The aim is to assist clinicians with a tool for selecting prospective antiviral treatments. Since the virus is known to mutate fast, the tool is likely to help clinicians in selecting the right set of antivirals for the mutated isolate. The main contribution of this work is a manually curated database publicly shared, comprising of existing associations between viruses and their corresponding antivirals. The database gathers similarity information using the chemical structure of drugs and the genomic structure of viruses. Along with this database, we make available a set of state‑of‑the‑art computational drug re‑positioning tools based on matrix completion. The tools are frst analysed on a standard set of experimental protocols for drug target interactions. The best performing ones are applied for the task of re‑positioning antivirals for COVID‑19. These tools select six drugs out of which four are currently under various stages of trial, namely Remdesivir (as a cure), Ribavarin (in combination with others for cure), Umifenovir (as a prophylactic and cure) and Sofosbuvir (as a cure).
    [Show full text]
  • Anti-Rhinovirus and Anti-Influenza Virus Activities Of
    Anti-rhinovirus and anti-inuenza virus activities of mucoactive secretolytic agents and plant extracts – a comparative in vitro study Christin Walther Jena University Hospital Michaela Schmidtke ( [email protected] ) Jena University Hospital https://orcid.org/0000-0001-9163-5682 Research Keywords: Acute respiratory infection, virus, rhinovirus, inuenza virus, natural products, over-the-counter medication, cytotoxicity, antiviral activity Posted Date: February 13th, 2020 DOI: https://doi.org/10.21203/rs.2.23461/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/10 Abstract Background: Rhinoviruses and inuenza viruses cause the majority of acute respiratory infections (ARIs). Symptoms of ARIs are commonly treated with over-the-counter products like ambroxol, bromhexine, and N-acetylcysteine, as well as thyme and pelargonium extracts. Because the antiviral activity of these over-the-counter products has not been studied in a systematic way, the current study aimed to compare their antiviral effect against two rhinovirus and two inuenza virus strains in an in vitro setting. Methods: The cytotoxicity of ambroxol, bromhexine, and N-acetylcysteine, as well as of thyme and pelargonium extracts was analyzed in Madin- Darby canine kidney (MDCK) and HeLa cells. The antiviral effect of these over-the-counter products was compared by analyzing the dose- dependent inhibition (i) of rhinovirus A2- and B14-induced cytopathic effect in HeLa cells and (ii) of inuenza virus A/Hong Kong/68 (subtype H3N2)- and A/Jena/8178/09 (subtype H1N1, pandemic)-induced cytopathic effect in MDCK cells at non-cytotoxic concentrations. Results: The results revealed a good compatibility (no or only marginal cytotoxicity in MDCK and HeLa cells) of the agents that were tested.
    [Show full text]
  • Zanamivir for Influenza in Adults and Children: Systematic Review of Clinical Study Reports and Summary of Regulatory Comments OPEN ACCESS
    BMJ 2014;348:g2547 doi: 10.1136/bmj.g2547 (Published 9 April 2014) Page 1 of 16 Research BMJ: first published as 10.1136/bmj.g2547 on 9 April 2014. Downloaded from RESEARCH Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments OPEN ACCESS 1 Carl J Heneghan professor of evidence based medicine , Igho Onakpoya research fellow in evidence 1 based practice and pharmacovigilance , Matthew Thompson Helen D Cohen endowed professorship 2 1 in family medicine , Elizabeth A Spencer nutritional epidemiologist , Mark Jones senior research 3 4 fellow (biostatistics) , Tom Jefferson reviewer 1Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK; 2Department of Family Medicine, University of Washington, Seattle, USA; 3School of Population Health, University of Queensland, Brisbane, Australia; 4Cochrane Acute Respiratory Infections Group, Via Puglie 23, 00187 Rome, Italy http://www.bmj.com/ Abstract (risk difference 0.17%, −0.73% to 0.70%) or radiologically confirmed Objectives To describe the potential benefits and harms of zanamivir. pneumonia (−0.06%, −6.56% to 2.11%) in adults. The effect on pneumonia in children was also not significant (0.56%, −1.64% to 1.04%). Design Systematic review of clinical study reports of randomised placebo There was no significant effect on otitis media or sinusitis in both adults controlled trials and regulatory information and children, with only a small effect noted for bronchitis in adults (1.80%, Data sources Clinical study reports, trial registries, electronic databases, 0.65% to 2.80%), but not in children. There were no data to assess regulatory archives, and correspondence with manufacturers.
    [Show full text]