The COVID-19 pandemic has evidenced the urgent need for the discovery of broad- spectrum antiviral therapies that could be deployed in the case of future emergence of novel viral threats, as well as to back up current therapeutic options in the case of drug resistance development. Most current antivirals are directed to inhibit specific viruses since these therapeutic molecules are designed to act on a specific viral target with the objective of interfering with a precise step in the replication cycle. Therefore, antimicrobial peptides (AMPs) have been identified as promising antiviral agents that could help to overcome this limitation and provide compounds able to act on more than a single viral family. We evaluated the antiviral activity of an amphibian peptide known for its strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, namely Temporin L (TL). Previous studies have revealed that TL is endowed with widespread antimicrobial activity and possesses marked haemolytic activity. Therefore, we analyzed TL and a previously identified TL derivative (Pro3, DLeu9 TL, where glutamine at position 3 is replaced with proline, and the D-Leucine enantiomer is present at position 9) as well as its analogs, for their activity against a wide panel of viruses comprising enveloped, naked, DNA and RNA viruses. We report significant inhibition activity against herpesviruses, paramyxoviruses, influenza virus and coronaviruses, including SARS-CoV-2. Moreover, we further modified our best candidate by lipidation and demonstrated a highly reduced cytotoxicity with improved antiviral effect. Our results show a potent and selective antiviral activity of TL peptides, indicating that the novel lipidated temporin-based antiviral agents could prove to be useful additions to current drugs in combatting rising drug resistance and epidemic/pandemic emergencies.

Broad-spectrum antiviral activity of the amphibian antimicrobial peptide temporin L and its analogs / Zannella, Carla; Chianese, Annalisa; Palomba, Luciana; Marcocci, Maria Elena; Bellavita, Rosa; Merlino, Francesco; Grieco, Paolo; Folliero, Veronica; De Filippis, Anna; Mangoni, Maria Luisa; Nencioni, Lucia; Franci, Gianluigi; Galdiero, Massimiliano. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:4(2022), pp. 1-23. [10.3390/ijms23042060]

Broad-spectrum antiviral activity of the amphibian antimicrobial peptide temporin L and its analogs

Maria Elena Marcocci;Maria Luisa Mangoni;Lucia Nencioni;
2022

Abstract

The COVID-19 pandemic has evidenced the urgent need for the discovery of broad- spectrum antiviral therapies that could be deployed in the case of future emergence of novel viral threats, as well as to back up current therapeutic options in the case of drug resistance development. Most current antivirals are directed to inhibit specific viruses since these therapeutic molecules are designed to act on a specific viral target with the objective of interfering with a precise step in the replication cycle. Therefore, antimicrobial peptides (AMPs) have been identified as promising antiviral agents that could help to overcome this limitation and provide compounds able to act on more than a single viral family. We evaluated the antiviral activity of an amphibian peptide known for its strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, namely Temporin L (TL). Previous studies have revealed that TL is endowed with widespread antimicrobial activity and possesses marked haemolytic activity. Therefore, we analyzed TL and a previously identified TL derivative (Pro3, DLeu9 TL, where glutamine at position 3 is replaced with proline, and the D-Leucine enantiomer is present at position 9) as well as its analogs, for their activity against a wide panel of viruses comprising enveloped, naked, DNA and RNA viruses. We report significant inhibition activity against herpesviruses, paramyxoviruses, influenza virus and coronaviruses, including SARS-CoV-2. Moreover, we further modified our best candidate by lipidation and demonstrated a highly reduced cytotoxicity with improved antiviral effect. Our results show a potent and selective antiviral activity of TL peptides, indicating that the novel lipidated temporin-based antiviral agents could prove to be useful additions to current drugs in combatting rising drug resistance and epidemic/pandemic emergencies.
2022
antimicrobial peptides; amps; temporins; antiviral activity; virus-host interaction; hsv-1; sars-cov-2; frog peptides
01 Pubblicazione su rivista::01a Articolo in rivista
Broad-spectrum antiviral activity of the amphibian antimicrobial peptide temporin L and its analogs / Zannella, Carla; Chianese, Annalisa; Palomba, Luciana; Marcocci, Maria Elena; Bellavita, Rosa; Merlino, Francesco; Grieco, Paolo; Folliero, Veronica; De Filippis, Anna; Mangoni, Maria Luisa; Nencioni, Lucia; Franci, Gianluigi; Galdiero, Massimiliano. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:4(2022), pp. 1-23. [10.3390/ijms23042060]
File allegati a questo prodotto
File Dimensione Formato  
Zannella_Broad-spectrum_2022.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.94 MB
Formato Adobe PDF
1.94 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1612017
Citazioni
  • ???jsp.display-item.citation.pmc??? 25
  • Scopus 37
  • ???jsp.display-item.citation.isi??? 34
social impact