Special Issue "Antivirals"

Guest Editor
Prof. Dr. Ulrich Jordis
Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163, A-1060 Wien, Austria
Website: http://phoenix.tuwien.ac.at/
E-Mail:
Phone: +43 1 58801 15460
Fax: +43 1 58801 15499
Interests: antivirals; Alzheimer; quinolones; combinatorial chemistry; labelled compounds; natural products (alkaloids; triterpenes); custom synthesis; chemistry software and databases

Molecules and Pharmaceuticals, being pioneer journals of web-based publications, invites you to submit research articles and comprehensive reviews addressing the discovery and/or development of antiviral agents in animals and man as well as in plants or lower organisms. Despite the tremendous successes and hallmarks e.g. in treating AIDS, clearly there is an ongoing and increased challenge to cope with the evolutionary and constantly changing threats of viral infections that have even the potential to ultra-risks for the mankind. Natural products continue to provide important leads and structures for the development of antiviral compounds and insights into the biochemical pathways and cell live cycles provide new starting points for new antiviral mechanisms. This issue intends to delineate the efforts being made to develop new and effective broad-spectrum antiviral agents e.g. for the treatment of HSV, VZV, HIV, HBV and DNA virus infections.

Prof. Dr. Ulrich Jordis
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 CHF (Swiss Francs).

Related Special Issue

Type of Paper: Review
Title: Current Status and Future of Influenza Vaccine and Related Patents
Authors: Jae-Min Song ¹ and Baik-Lin Seong ²
Affiliations: ¹ Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA; E-Mail: jaemin@yonsei.ac.kr (J.-M.S.)
² Department of Biotechnology College of Life Science and Biotechnology, Yonsei University, Seoul, Korea; E-Mail: blseong@yonsei.ac.kr (B.-L.S.)
Abstract: The threat of a major human influenza pandemic, in particular from highly aggressive strains such as avian H5N1 or 2009 swine origin H1N1, has emphasized the need for therapeutic strategies to combat these pathogens. Although egg based influenza vaccine production has been well established for more than 20 years, developing new influenza vaccines with improved safety, efficacy and ease of administration compared with conventional influenza vaccines is ongoing public health need. This article is intended to cover some recent advances and related patents on the development influenza vaccine including live attenuated, cell based, DNA and synthetic peptide vaccines.

Type of Paper: Article
Title: Inhibition of Human Rhinovirus Replication in Mice by Highly Selective Small Interfering RNA
Authors: Romy Zieger, Julia Gebhardt, Katrin Jäger, Ivonne Robel, Kristine Hille, Christiane Petzold and Jacques Rohayem
Affiliations: ¹ Institute of Virology, University of Technology, Fielderstrasse 42, 01309 Dresden, Germany
² Riboxx GmbH, Pharmapark Radebeul, Meissner Strasse 191, D-01445 Radebeul, Germany; E-Mail: Jacques.Rohayem@riboxx.com (J.R.)
Abstract: Human rhinoviruses (HRV) are the predominant agent of the common cold and are responsible for a majority of lower and upper respiratory diseases. Despite significant efforts, no antiviral agents have been so far approved for the prevention or treatment of HRV-infection. RNA interference is an innovative approach for silencing viral gene expression in mammalian cells. In this study, we report an efficient inhibition of HRV-replication in vitro as well as in the respiratory tract of mice through administration of highly selective small interfering RNA. We designed 19 siRNAs targeting the entire genome of the HRV type 1B. The siRNA harbored the innovative riboxx® sequence motive. On HeLa monolayers infected with HRV 1B, virus specific siRNAs showed a dose-dependent antiviral effect. In comparison to conventional siRNA with 3'-overhangs (T-siRNA) which target the same genome region, the riboxx siRNA (RBX-siRNA) displayed in vitro a 5-fold increase in potency (i.e. IC50 for RBX-10: 37.5 nM vs. T-10: 249 nM). In the next step, siRNA lead candidate RBX-10 was chosen for inhibition of HRV 1B replication in BALB/c mice. Animals were infected intra-nasally with 106 TCID50 HRV 1B and the viral load measured in the lower lobe of the left lung. Intra-nasal administration of RBX-siRNA (125 µM) in a prophylaxis model reduced the viral load at 48h, with a complete suppression at 96h. The experimental data in mice is a first step towards the development of potent RNAi-therapeutic agents aiming at controlling the infection with the human rhinovirus 1B.

Type of Paper: Article
Title: Characterization and Biological Evaluation of New Aramides Nanoparticles And Their Platinum And Palladium Complexes
Authors: Hammed H. A. M. Hassan and Amel F. Elhusseiny
Affiliations: Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 2-Moharram Beck, Alexandria-21568, Egypt;
E-Mail: hassan10@safwait.com. (H.H.A.M.H.)
Abstract: The production of new nano-materials has attracted significant attention in research and applications in areas including electronics, photonics, and biomedicine. In this work, we report the preparation of six new well-separated thermally stable spherical aramides nanoparticles with an average diameter 125 nm as judged by SEM. Reactions with palladium or platinum salts produced complexes with different stoichiometries and their proposed structures are based on their elementals, EDX, IR, UV, and thermal analyses. The antimicrobial screening against different pathogenic bacterial strains showed moderate activity as compared to the standard bactericide. The cytotoxicity of the complexes tested at one concentration against three cell lines of human cancer showed high potency against HCT116 and MCF7 while moderately potent against HEPG2.

Type of Paper: Review
Title: Cationic Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Infection
Authors: Shawn Keogan ¹, Mohamed Labib ², Brian Wigdahl ¹ and Fred C. Krebs ¹
Affiliations: ¹ Department of Microbiology and Immunology, and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia (PA), USA
² Novaflux Technologies, Inc., Princeton, NJ, USA; E-Mail: Fred.Krebs@DrexelMed.edu (F.K.)
Abstract: Charge has been a long-standing consideration in the discovery, design, and development of molecules effective against the human immunodeficiency virus type 1 (HIV-1). Some of the earliest inhibitors of HIV-1, such as suramin, dextran sulfate, and heparin, possessed antiviral activities that were directly attributable to their polyanionic charges. More recent developmental efforts have been devoted to discovering and evaluating HIV-1 inhibitors that are prominently cationic. This family of molecules includes synthetic peptides, natural proteins and peptides, and organic molecules. This review provides an overview of each cationic molecule, its activity against HIV-1, and its potential as a therapeutic agent.

Type of Paper: Review
Title: Lactoferrin: An Antiviral Molecule of Natural Immunity
Authors: Francesca Berlutti ¹, Fabrizio Pantanella ¹, Tiziana Natalizi ¹, Alessandra Frioni ¹, Rosalba Paesano ^2,3 and Piera Valenti ¹
Affiliations: ¹ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy; E-Mail: piera.valenti@uniroma1.it (P.V.)
² Department of Obstetrician and Gynaecology, Sapienza University of Rome, Rome, Italy
³ Clinica ‘‘Fabia Mater’’, Rome, Italy
Abstract: Lactoferrin (Lf) is a cationic iron binding glycoprotein present in several mucosal secretions synthesized by exocrine glands and neutrophils in infection and inflammation sites. Lf is a multifunctional glycoprotein, which plays an important role in immune regulation and defence mechanisms against bacteria, fungi and viruses. Lf iron-withholding ability is related to inhibition of microbial growth as well as to modulation of motility, aggregation and biofilm formation of pathogenic bacteria. Conversely, independently on iron binding capability, this cationic protein interacts with microbial, viral and cell surfaces thus inhibiting microbial and viral adhesion and entry into host cells. Lf can be considered not only a primary defense factor against mucosal infections, but also a polyvalent regulator which interacts in viral infectious processes. The antiviral activity of Lf, demonstrated against both enveloped and naked viruses, lies in the early phase of infection, thus preventing entry of virus in the host cell. This activity is exerted by binding to heparan sulphate (HS) glycosaminoglycans (GAGs) cell receptors, or viral particles or both. Although the antiviral effect of Lf, widely demonstrated in vitro studies, is one of its major biological functions, few clinical trials have been carried out and the related mechanism of action is still under debate. Recently, it has been found the nuclear localization of Lf in different epithelial human cells thus suggesting that Lf exerts its antiviral effect not only in the early phase of surface interaction virus-cell but also intracellularly. As matter of fact, Lf blocks nuclear export of viral ribonucleoproteins so preventing viral assembly of Influenza A virus as well as it interferes with intracellular trafficking of Herpes simplex virus-1. Finally, the capability of Lf to exert a potent antiviral activity, through its binding to host cells and/or viral particles, and its nuclear localization strengthens the idea that this glycoprotein is an important brick in the mucosal wall, effective against viral attacks and it could be usefully applied as novel strategy for treatment of viral infections.

Type of Paper: Review
Title: Echinacea as a Source of Potent Antivirals for Respiratory Virus Infections
Authors: James B. Hudson and Selvarani Vimalanathan
Affiliation: Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, Canada; E-Mail: jbhudson@interchange.ubc.ca (J.B.H.)
Abstract: Extracts of Echinacea species have been used traditionally in North America for the control of symptoms of colds, influenza, and other diseases, and some of them have become very popular recently as “herbal medicines”. Our studies revealed that  preparations derived from certain species and plant parts, but not all of them, possess potent  antiviral activities, particularly against membrane containing viruses. Thus all strains of influenza virus tested (including a Tamiflu-resistant strain), and HSV-1, respiratory syncytial virus, and rhinoviruses were very susceptible to a standardized Echinacea purpurea preparation. In mechanistic studies the influenza virus-specific hemagglutinin and neuraminidase were inhibited, but interferon genes were not involved. Multiple components of the extract appeared to be responsible for the antiviral activities.

Type of Paper: Review
Title: Novel HIV Fusion Inhibitory Peptides: Design for the Next Generation
Authors: Fusako Miyamoto and Eiichi N. Kodama
Affiliation: Division of Emerging Infectious Diseases, Department of Internal Medicine, Tohoku University School of Medicine, Sendai 980-8575, Japan;
E-Mail: kodama515@med.tohoku.ac.jp (E.N.K.)
Abstract: Development of numerous compounds for HIV-1 therapy provides efficient and successful suppression of HIV-1 replication. In addition to previous targets reverse transcriptase (RT) and protease (Pro), new targets, such as Integrase, fusion, and CCR5 are well developed and effectively suppress not only drug naive but also drug experienced HIV-1 multidrug resistant to RT and pro inhibitors. In this review, fusion inhibitors are discussed. Enfvirtide (T-20) comprising 36 amino acids**derived from gp41 HIV-1 C-HR has been approved in 2003 as the first HIV-1 fusion inhibitor, which is a unique and novel class inhibitor for HIV-1 therapy. T-20 well suppress HIV-1 replication including resistant variants to RT and Pro inhibitors. However, after prolonged therapy with T-20, HIV-1 acquires resistance to T-20. To suppress these HIV-1 variants, we and other groups have been tried to fight with the resistance by development of the modified fusion inhibitors, termed the 2nd generation fusion inhibitors. In this review, we will discuss the 2nd generation inhibitors.

Type of Paper: Review
Title: Metal Nanoparticles as Antiviral Agents
Authors: Galdiero Stefania ^2,3,4, Falanga Annarita ², Vitiello Mariateresa ¹, Cantisani Marco ², Marra Veronica ¹, Galdiero Massimiliano ^1,3
Affiliations: ¹ Department of Experimental Medicine - II University of Naples, Via De Crecchio 7, 80138, Napoli, Italy
² Department of Biological Sciences, Division of Biostructures and
³ Centro Interuniversitario di Ricerca sui Peptidi Bioattivi - University of Naples "Federico II", Via Mezzocannone 16, 80134, Napoli, Italy
⁴ Istituto di Biostrutture e Bioimmagini - CNR, Via Mezzocannone 16, 80134, Napoli, Italy; E-Mail: massimilianogaldiero@unina2.it (G.M.)
Abstract: Virus infections pose significant global health challenges, expecially in view of the fact that the emergence of resistant viral strains and the adverse side effects associated with prolonged use continue to slow down the application of effective antiviral therapies. This makes imperative the need for the development of safe and potent antiviral alternatives to conventional antiviral drugs. In the present scenario, nanoscale materials have emerged up as novel antiviral agents for the possibilities offered by their unique chemical and physical properties. Metal nanoparticles have mainly been studied for their antimicrobial potential against bacteria but have also proven to be active against several types of viruses including human imunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey pox virus. The use of metal nanoparticles provide an interesting feature for novel antiviral that is the low possibility to develop resistance against the metal nanoparticle as compared to conventional antivirals as metals may attack a broad range of targets in the virus.The present review focuses on the development of methods for biosynthesis of metal nanoparticles and their use as antiviral therapeutics against pathogenic viruses.