Hylin-a1: A Pan-Inhibitor against Emerging and Re-Emerging Respiratory Viruses

Pandemic and epidemic outbreaks of respiratory viruses are a challenge for public health and social care system worldwide, leading to high mortality and morbidity among the human populations. In light of the limited efficacy of current vaccines and antiviral drugs against respiratory viral infections and the emergence and re-emergence of new viruses, novel broad-spectrum antiviral drugs are needed for the prevention and treatment of these infections. Antimicrobial peptides with an antiviral effect, also known as AVPs, have already been reported as potent inhibitors of viral infections by affecting different stages of the virus lifecycle. In the present study, we analyzed the activity of the AVP Hylin-a1, secreted by the frog Hypsiboas albopunctatus, against a wide range of respiratory viruses, including the coronaviruses HCoV-229E and SARS-CoV-2, measles virus, human parainfluenza virus type 3, and influenza virus H1N1. We report a significant inhibitory effect on infectivity in all the enveloped viruses, whereas there was a lack of activity against the naked coxsackievirus B3. Considering the enormous therapeutic potential of Hylin-a1, further experiments are required to elucidate its mechanism of action and to increase its stability by modifying the native sequence.

[1]  V. Iovane,et al.  Synthetic Frog-Derived-like Peptides: A New Weapon against Emerging and Potential Zoonotic Viruses , 2023, Viruses.

[2]  M. Galdiero,et al.  Hylin-a1: A Host Defense Peptide with Antibacterial Potential against Staphylococcus aureus Multi-Resistant Strains , 2023, Pharmaceuticals.

[3]  Po-Yu Liu,et al.  The Impact of the COVID-19 Pandemic on Respiratory Syncytial Virus Infection: A Narrative Review , 2023, Infection and drug resistance.

[4]  G. Fragneto,et al.  How do antimicrobial peptides disrupt the lipopolysaccharide membrane leaflet of Gram-negative bacteria? , 2023, Journal of colloid and interface science.

[5]  G. Balasubramani,et al.  Population‐based hospitalization burden estimates for respiratory viruses, 2015–2019 , 2022, Influenza and other respiratory viruses.

[6]  Yoonkyung Park,et al.  Bactericidal activities and Action mechanism of the Novel Antimicrobial Peptide Hylin a1 and its analog peptides against Acinetobacter baumannii infection. , 2022, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[7]  L. Sukmarini Antiviral Peptides (AVPs) of Marine Origin as Propitious Therapeutic Drug Candidates for the Treatment of Human Viruses , 2022, Molecules.

[8]  P. Grieco,et al.  Broad-Spectrum Antiviral Activity of the Amphibian Antimicrobial Peptide Temporin L and Its Analogs , 2022, International journal of molecular sciences.

[9]  M. Galdiero,et al.  The Broad-Spectrum Antiviral Potential of the Amphibian Peptide AR-23 , 2022, International journal of molecular sciences.

[10]  P. Grieco,et al.  Antimicrobial Activity of a Lipidated Temporin L Analogue against Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates , 2021, Antibiotics.

[11]  J. Coia,et al.  Herpes Simplex Virus Type 1 Pneumonia—A Review , 2021, Journal of intensive care medicine.

[12]  Jie Yang,et al.  Antiviral activity and mechanism of ESC-1GN from skin secretion of hylarana guentheri against influenza a virus. , 2021, Journal of biochemistry.

[13]  E. Novellino,et al.  Temporin G, an amphibian antimicrobial peptide against influenza and parainfluenza respiratory viruses: Insights into biological activity and mechanism of action , 2021, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  S. Henriques,et al.  Mode-of-Action of Antimicrobial Peptides: Membrane Disruption vs. Intracellular Mechanisms , 2020, Frontiers in Medical Technology.

[15]  A. Romanelli,et al.  Antibiofilm Properties of Temporin-L on Pseudomonas fluorescens in Static and In-Flow Conditions , 2020, International journal of molecular sciences.

[16]  N. Subbarao,et al.  Envelope proteins as antiviral drug target , 2020, Journal of drug targeting.

[17]  R. Dutch,et al.  Viral Membrane Fusion and the Transmembrane Domain , 2020, Viruses.

[18]  Xueqing Xu,et al.  Esc‐1GN shows therapeutic potentials for acne vulgaris and inflammatory pain , 2020, Journal of peptide science : an official publication of the European Peptide Society.

[19]  Jie Yang,et al.  Antioxidant properties and neuroprotective effects of Ecs-1GN through the regulation of MAPK and AKT signaling. , 2020, Life sciences.

[20]  G. Diamond,et al.  Antiviral Activities of Human Host Defense Peptides. , 2020, Current medicinal chemistry.

[21]  M. Loffredo,et al.  The Potential of Frog Skin Peptides for Anti-Infective Therapies: the Case of Esculentin-1a(1-21)NH2. , 2020, Current medicinal chemistry.

[22]  B. Kampmann,et al.  The burden of viral respiratory infections in young children in low-resource settings. , 2020, The Lancet. Global health.

[23]  M. Lucero,et al.  Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study , 2020, The Lancet. Global health.

[24]  N. Chiu,et al.  Increased Detection of Viruses in Children with Respiratory Tract Infection Using PCR , 2020, International journal of environmental research and public health.

[25]  J. Leprince,et al.  Peptidomic analysis in the discovery of therapeutically valuable peptides in amphibian skin secretions , 2019, Expert review of proteomics.

[26]  Yasuhiko Irie,et al.  Discovery and development of safe-in-man broad-spectrum antiviral agents , 2019, International Journal of Infectious Diseases.

[27]  Giulio Superti-Furga,et al.  Common Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis , 2019, Front. Immunol..

[28]  M. L. Campos,et al.  Antiviral peptides as promising therapeutic drugs , 2019, Cellular and Molecular Life Sciences.

[29]  Xueqing Xu,et al.  Functional Characterization of a Novel Lipopolysaccharide-Binding Antimicrobial and Anti-Inflammatory Peptide in Vitro and in Vivo. , 2018, Journal of medicinal chemistry.

[30]  W. Rodriguez-Cintron,et al.  Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  Sanil George,et al.  Identification and characterization of novel host defense peptides from the skin secretion of the fungoid frog, Hydrophylax bahuvistara (Anura: Ranidae) , 2018, Chemical biology & drug design.

[32]  F. Rey,et al.  Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines , 2018, Cell.

[33]  P. Grieco,et al.  The Amphibian Antimicrobial Peptide Temporin B Inhibits In Vitro Herpes Simplex Virus 1 Infection , 2018, Antimicrobial Agents and Chemotherapy.

[34]  C. Jallet,et al.  Dermaseptins as potential antirabies compounds. , 2018, Vaccine.

[35]  S. Duwe Influenza viruses – antiviral therapy and resistance , 2017, GMS infectious diseases.

[36]  Florian Krammer,et al.  An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin‐Bearing Influenza Viruses , 2017, Immunity.

[37]  A. Caporale,et al.  Evaluation of combined use of Oxyma and HATU in aggregating peptide sequences , 2017, Journal of peptide science : an official publication of the European Peptide Society.

[38]  P. Del Vecchio,et al.  Antimicrobial peptides at work: interaction of myxinidin and its mutant WMR with lipid bilayers mimicking the P. aeruginosa and E. coli membranes , 2017, Scientific Reports.

[39]  F. Salvatore,et al.  Design and activity of a cyclic mini-β-defensin analog: a novel antimicrobial tool , 2015, International journal of nanomedicine.

[40]  Benhur Lee,et al.  Broad-spectrum antivirals against viral fusion , 2015, Nature Reviews Microbiology.

[41]  Elena Bekerman,et al.  Combating emerging viral threats , 2015, Science.

[42]  M. Lukic,et al.  Potential therapeutic applications of multifunctional host-defense peptides from frog skin as anti-cancer, anti-viral, immunomodulatory, and anti-diabetic agents , 2014, Peptides.

[43]  M. Vignuzzi,et al.  Ribavirin: a drug active against many viruses with multiple effects on virus replication and propagation. Molecular basis of ribavirin resistance , 2014, Current Opinion in Virology.

[44]  D. Hayes,et al.  Respiratory syncytial virus: current and emerging treatment options , 2014, ClinicoEconomics and outcomes research : CEOR.

[45]  G. Morelli,et al.  Peptide inhibitors against herpes simplex virus infections , 2013, Journal of peptide science : an official publication of the European Peptide Society.

[46]  F. Tangy,et al.  In vitro antiviral activity of dermaseptin S4 and derivatives from amphibian skin against herpes simplex virus type 2 , 2013, Journal of medical virology.

[47]  R. Booy,et al.  Emergence of oseltamivir resistance: control and management of influenza before, during and after the pandemic. , 2013, Infectious disorders drug targets.

[48]  J. Englund,et al.  Emerging oseltamivir resistance in seasonal and pandemic influenza A/H1N1. , 2011, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[49]  Isaiah T Arkin,et al.  Resistance characteristics of influenza to amino-adamantyls. , 2011, Biochimica et biophysica acta.

[50]  H. Atkins,et al.  A carpet-based mechanism for direct antimicrobial peptide activity against vaccinia virus membranes , 2010, Peptides.

[51]  G. Castaldo,et al.  Novel Synthetic, Salt-Resistant Analogs of Human Beta-Defensins 1 and 3 Endowed with Enhanced Antimicrobial Activity , 2010, Antimicrobial Agents and Chemotherapy.

[52]  Robert Damoiseaux,et al.  A broad-spectrum antiviral targeting entry of enveloped viruses , 2010, Proceedings of the National Academy of Sciences.

[53]  M. Galdiero,et al.  Inhibition of viral-induced membrane fusion by peptides. , 2009, Protein and peptide letters.

[54]  C. Ricart,et al.  Hylin a1, the first cytolytic peptide isolated from the arboreal South American frog Hypsiboas albopunctatus (“spotted treefrog”) , 2009, Peptides.

[55]  Kathryn L. Schornberg,et al.  Structures and Mechanisms of Viral Membrane Fusion Proteins: Multiple Variations on a Common Theme , 2008 .

[56]  J. Feix,et al.  Peptide-membrane interactions and mechanisms of membrane destruction by amphipathic alpha-helical antimicrobial peptides. , 2006, Biochimica et biophysica acta.

[57]  D. Barra,et al.  Interaction of Antimicrobial Peptide Temporin L with Lipopolysaccharide In Vitro and in Experimental Rat Models of Septic Shock Caused by Gram-Negative Bacteria , 2006, Antimicrobial Agents and Chemotherapy.

[58]  F. Tangy,et al.  The antimicrobial peptide dermaseptin S4 inhibits HIV-1 infectivity in vitro. , 2005, Virology.

[59]  P. F. Nielsen,et al.  A family of brevinin-2 peptides with potent activity against Pseudomonas aeruginosa from the skin of the Hokkaido frog, Rana pirica , 2004, Regulatory Peptides.

[60]  Vanesa C Albiol Matanic,et al.  Antiviral activity of antimicrobial cationic peptides against Junin virus and herpes simplex virus. , 2004, International journal of antimicrobial agents.

[61]  D. Barra,et al.  Functional characterisation of the 1–18 fragment of esculentin-1b, an antimicrobial peptide from Rana esculenta , 2003, Peptides.

[62]  P. Mackie The classification of viruses infecting the respiratory tract , 2003, Paediatric Respiratory Reviews.

[63]  P. Kinnunen,et al.  Temporin L: antimicrobial, haemolytic and cytotoxic activities, and effects on membrane permeabilization in lipid vesicles. , 2002, The Biochemical journal.

[64]  M. Aouni,et al.  In vitro antiviral activity of dermaseptins against herpes simplex virus type 1 * , 2002, Journal of medical virology.

[65]  F. Bossa,et al.  Antimicrobial peptides from skin secretions of Rana esculenta. Molecular cloning of cDNAs encoding esculentin and brevinins and isolation of new active peptides. , 1994, The Journal of biological chemistry.

[66]  OUP accepted manuscript , 2021, Clinical Infectious Diseases.

[67]  W. Fontes,et al.  Influence of N‐terminus modifications on the biological activity, membrane interaction, and secondary structure of the antimicrobial peptide hylin‐a1 , 2011, Biopolymers.

[68]  H. Oshitani,et al.  Emergence of amantadine-resistant influenza A viruses: epidemiological study , 2003, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.