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Antiviral and Antimicrobial Peptides

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 22549

Special Issue Editors

Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Interests: peptides; anti-viral peptide; anti-bacterial peptide
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The current outbreak of the new coronavirus (SARS-CoV-2) responsible for the COVID-19 pandemic has emphasized how infectious diseases continue to be a serious global health problem with meaningful epidemiological, financial, and strategic implications. Emerging infections are a major concern for any healthcare system around the world, and we must face the drastic reality of the increasing resistance to antibiotics of multidrug-resistant bacterial strains. For various reasons, antibacterial and antiviral weapons to fight back are, nowadays, in short supply. In fact, apart from HIV, some hepatitis viruses, and a few other viruses, our therapeutic arsenal to combat viral infections remains very limited as do the options available against multi-resistant bacteria (only a handful of novel antibiotics have been licensed in the last two decades). Therefore, the identification of new molecules and therapies to combat emerging multi-resistant bacteria and viruses is urgently required. A very promising therapeutic strategy against various microbial species is represented by antimicrobial peptides (AMPs), which generally play a key role in the innate immune system of higher organisms. AMPs represent the first line of protection and response against opportunistic and pathogenic microorganisms in nature.

In recent decades, AMPs have earned extensive consideration as potential new therapeutic molecules. In fact, it has been shown that they are active against both Gram-positive and Gram-negative pathogens and, also, against fungi at low micromolar concentrations, demonstrating rapid killing action mainly targeting the bacterial membrane though, recently, a large amount of data is also accumulating on their antiviral activity. Nevertheless, the use of AMPs in the clinical setting has been thwarted by their low bioavailability and great metabolic instability. However, recent technical advances (mainly peptidomimetics) have shown the way to improve activity profiles and stability, opening up the possibility for these new molecules to reach the market.

We welcome you to submit manuscripts that describe new antibacterial and/or antiviral peptides with special attention to the determination of their structure, their rational design, modification, and peptidomimetics, and the study of their interaction mechanisms with target microbes (mainly bacteria and viruses but also yeasts, fungi, and parasites) at cellular and molecular levels. For this Special Issue entitled “Antiviral and Antimicrobial Peptides”, we invite authors to submit original or review articles covering all aspects of this topic.

Prof. Massimiliano Galdiero
Prof. Gianluigi Franci
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Peptides
  • AMPs
  • Antimicrobial
  • Antiviral
  • Emerging infections
  • Peptidomimetics

Published Papers (8 papers)

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Research

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16 pages, 3138 KiB  
Article
Selective Inhibition of Murine Cytomegalovirus Viral Gene Expression by the Antiviral Peptide TAT-I24
by Hanna Harant
Int. J. Mol. Sci. 2022, 23(13), 7246; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137246 - 29 Jun 2022
Viewed by 1634
Abstract
The effect of the antiviral peptide TAT-I24 on viral gene expression in cells infected with murine cytomegalovirus (MCMV) was investigated. The expression of immediate-early, early and late genes was highly induced upon infection with MCMV. In the presence of the peptide, the expression [...] Read more.
The effect of the antiviral peptide TAT-I24 on viral gene expression in cells infected with murine cytomegalovirus (MCMV) was investigated. The expression of immediate-early, early and late genes was highly induced upon infection with MCMV. In the presence of the peptide, the expression of all tested genes was sustainably reduced to a similar extent, independent of whether they were immediate-early, early or late genes. In contrast, the expression of host genes, such as NF-κB inhibitor alpha (Nfkbia), interferon-induced protein with tetratricopeptide repeats 1 (Ifit1), chemokine (C-X-C motif) ligand 10 (Cxcl10), chemokine (C-C motif) ligand 7 (Ccl7) and chemokine (C-C motif) ligand 5 (Ccl5), which are induced early upon virus infection, was only transiently suppressed in peptide-treated cells. The expression of other host genes which are affected by MCMV infection and play a role in endoplasmic reticulum stress or DNA-damage repair was not inhibited by the peptide. A combination of TAT-I24 with the nucleoside analogue cidofovir showed enhancement of the antiviral effect, demonstrating that viral replication can be more efficiently inhibited with a combination of drugs acting at different stages of the viral life-cycle. Full article
(This article belongs to the Special Issue Antiviral and Antimicrobial Peptides)
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23 pages, 1921 KiB  
Article
Broad-Spectrum Antiviral Activity of the Amphibian Antimicrobial Peptide Temporin L and Its Analogs
by Carla Zannella, Annalisa Chianese, Luciana Palomba, Maria Elena Marcocci, Rosa Bellavita, Francesco Merlino, Paolo Grieco, Veronica Folliero, Anna De Filippis, Marialuisa Mangoni, Lucia Nencioni, Gianluigi Franci and Massimiliano Galdiero
Int. J. Mol. Sci. 2022, 23(4), 2060; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042060 - 13 Feb 2022
Cited by 32 | Viewed by 3002
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Antiviral and Antimicrobial Peptides)
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15 pages, 2994 KiB  
Article
The Peptide A-3302-B Isolated from a Marine Bacterium Micromonospora sp. Inhibits HSV-2 Infection by Preventing the Viral Egress from Host Cells
by Sanya Sureram, Irene Arduino, Reiko Ueoka, Massimo Rittà, Rachele Francese, Rattanaporn Srivibool, Dhanushka Darshana, Jörn Piel, Somsak Ruchirawat, Luisa Muratori, David Lembo, Prasat Kittakoop and Manuela Donalisio
Int. J. Mol. Sci. 2022, 23(2), 947; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020947 - 15 Jan 2022
Cited by 10 | Viewed by 3106
Abstract
Herpesviruses are highly prevalent in the human population, and frequent reactivations occur throughout life. Despite antiviral drugs against herpetic infections, the increasing appearance of drug-resistant viral strains and their adverse effects prompt the research of novel antiherpetic drugs for treating lesions. Peptides obtained [...] Read more.
Herpesviruses are highly prevalent in the human population, and frequent reactivations occur throughout life. Despite antiviral drugs against herpetic infections, the increasing appearance of drug-resistant viral strains and their adverse effects prompt the research of novel antiherpetic drugs for treating lesions. Peptides obtained from natural sources have recently become of particular interest for antiviral therapy applications. In this work, we investigated the antiviral activity of the peptide A-3302-B, isolated from a marine bacterium, Micromonospora sp., strain MAG 9-7, against herpes simplex virus type 1, type 2, and human cytomegalovirus. Results showed that the peptide exerted a specific inhibitory activity against HSV-2 with an EC50 value of 14 μM. Specific antiviral assays were performed to investigate the mechanism of action of A-3302-B. We demonstrated that the peptide did not affect the expression of viral proteins, but it inhibited the late events of the HSV-2 replicative cycle. In detail, it reduced the cell-to-cell virus spread and the transmission of the extracellular free virus by preventing the egress of HSV-2 progeny from the infected cells. The dual antiviral and previously reported anti-inflammatory activities of A-3302-B, and its effect against an acyclovir-resistant HSV-2 strain are attractive features for developing a therapeutic to reduce the transmission of HSV-2 infections. Full article
(This article belongs to the Special Issue Antiviral and Antimicrobial Peptides)
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18 pages, 5238 KiB  
Article
The Broad-Spectrum Antiviral Potential of the Amphibian Peptide AR-23
by Annalisa Chianese, Carla Zannella, Alessandra Monti, Anna De Filippis, Nunzianna Doti, Gianluigi Franci and Massimiliano Galdiero
Int. J. Mol. Sci. 2022, 23(2), 883; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020883 - 14 Jan 2022
Cited by 26 | Viewed by 2414
Abstract
Viral infections represent a serious threat to the world population and are becoming more frequent. The search and identification of broad-spectrum antiviral molecules is necessary to ensure new therapeutic options, since there is a limited availability of effective antiviral drugs able to eradicate [...] Read more.
Viral infections represent a serious threat to the world population and are becoming more frequent. The search and identification of broad-spectrum antiviral molecules is necessary to ensure new therapeutic options, since there is a limited availability of effective antiviral drugs able to eradicate viral infections, and consequently due to the increase of strains that are resistant to the most used drugs. Recently, several studies on antimicrobial peptides identified them as promising antiviral agents. In detail, amphibian skin secretions serve as a rich source of natural antimicrobial peptides. Their antibacterial and antifungal activities have been widely reported, but their exploitation as potential antiviral agents have yet to be fully investigated. In the present study, the antiviral activity of the peptide derived from the secretion of Rana tagoi, named AR-23, was evaluated against both DNA and RNA viruses, with or without envelope. Different assays were performed to identify in which step of the infectious cycle the peptide could act. AR-23 exhibited a greater inhibitory activity in the early stages of infection against both DNA (HSV-1) and RNA (MeV, HPIV-2, HCoV-229E, and SARS-CoV-2) enveloped viruses and, on the contrary, it was inactive against naked viruses (PV-1). Altogether, the results indicated AR-23 as a peptide with potential therapeutic effects against a wide variety of human viruses. Full article
(This article belongs to the Special Issue Antiviral and Antimicrobial Peptides)
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10 pages, 3037 KiB  
Article
25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses
by Qiaoshuai Lan, Chao Wang, Jie Zhou, Lijue Wang, Fanke Jiao, Yanbo Zhang, Yanxing Cai, Lu Lu, Shuai Xia and Shibo Jiang
Int. J. Mol. Sci. 2021, 22(21), 11869; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111869 - 01 Nov 2021
Cited by 14 | Viewed by 2625
Abstract
The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with [...] Read more.
The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity. Full article
(This article belongs to the Special Issue Antiviral and Antimicrobial Peptides)
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11 pages, 2714 KiB  
Article
Therapeutic Effect of an Antibody-Derived Peptide in a Galleria mellonella Model of Systemic Candidiasis
by Emerenziana Ottaviano, Elisa Borghi, Laura Giovati, Monica Falleni, Delfina Tosi, Walter Magliani, Giulia Morace, Stefania Conti and Tecla Ciociola
Int. J. Mol. Sci. 2021, 22(20), 10904; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222010904 - 09 Oct 2021
Cited by 6 | Viewed by 1443
Abstract
The synthetic peptide T11F (TCRVDHRGLTF), with sequence identical to a fragment of the constant region of human IgM, and most of its alanine-substituted derivatives proved to possess a significant candidacidal activity in vitro. In this study, the therapeutic efficacy of T11F, D5A, the [...] Read more.
The synthetic peptide T11F (TCRVDHRGLTF), with sequence identical to a fragment of the constant region of human IgM, and most of its alanine-substituted derivatives proved to possess a significant candidacidal activity in vitro. In this study, the therapeutic efficacy of T11F, D5A, the derivative most active in vitro, and F11A, characterized by a different conformation, was investigated in Galleria mellonella larvae infected with Candida albicans. A single injection of F11A and D5A derivatives, in contrast with T11F, led to a significant increase in survival of larvae injected with a lethal inoculum of C. albicans cells, in comparison with infected animals treated with saline. Peptide modulation of host immunity upon C. albicans infection was determined by hemocyte analysis and larval histology, highlighting a different immune stimulation by the studied peptides. F11A, particularly, was the most active in eliciting nodule formation, melanization and fat body activation, leading to a better control of yeast infection. Overall, the obtained data suggest a double role for F11A, able to simultaneously target the fungus and the host immune system, resulting in a more efficient pathogen clearance. Full article
(This article belongs to the Special Issue Antiviral and Antimicrobial Peptides)
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22 pages, 17418 KiB  
Article
Membrane Interactions of Latarcins: Antimicrobial Peptides from Spider Venom
by Parvesh Wadhwani, Saiguru Sekaran, Erik Strandberg, Jochen Bürck, Archana Chugh and Anne S. Ulrich
Int. J. Mol. Sci. 2021, 22(18), 10156; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810156 - 21 Sep 2021
Cited by 8 | Viewed by 2646
Abstract
A group of seven peptides from spider venom with diverse sequences constitute the latarcin family. They have been described as membrane-active antibiotics, but their lipid interactions have not yet been addressed. Using circular dichroism and solid-state 15N-NMR, we systematically characterized and compared [...] Read more.
A group of seven peptides from spider venom with diverse sequences constitute the latarcin family. They have been described as membrane-active antibiotics, but their lipid interactions have not yet been addressed. Using circular dichroism and solid-state 15N-NMR, we systematically characterized and compared the conformation and helix alignment of all seven peptides in their membrane-bound state. These structural results could be correlated with activity assays (antimicrobial, hemolysis, fluorescence vesicle leakage). Functional synergy was not observed amongst any of the latarcins. In the presence of lipids, all peptides fold into amphiphilic α-helices as expected, the helices being either surface-bound or tilted in the bilayer. The most tilted peptide, Ltc2a, possesses a novel kind of amphiphilic profile with a coiled-coil-like hydrophobic strip and is the most aggressive of all. It indiscriminately permeabilizes natural membranes (antimicrobial, hemolysis) as well as artificial lipid bilayers through the segregation of anionic lipids and possibly enhanced motional averaging. Ltc1, Ltc3a, Ltc4a, and Ltc5a are efficient and selective in killing bacteria but without causing significant bilayer disturbance. They act rather slowly or may even translocate towards intracellular targets, suggesting more subtle lipid interactions. Ltc6a and Ltc7, finally, do not show much antimicrobial action but can nonetheless perturb model bilayers. Full article
(This article belongs to the Special Issue Antiviral and Antimicrobial Peptides)
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Review

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33 pages, 20322 KiB  
Review
Antimicrobial Peptides with Antibacterial Activity against Vancomycin-Resistant Staphylococcus aureus Strains: Classification, Structures, and Mechanisms of Action
by Isabella Hernández-Aristizábal and Iván Darío Ocampo-Ibáñez
Int. J. Mol. Sci. 2021, 22(15), 7927; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157927 - 25 Jul 2021
Cited by 11 | Viewed by 3896
Abstract
The emergence of bacteria resistant to conventional antibiotics is of great concern in modern medicine because it renders ineffectiveness of the current empirical antibiotic therapies. Infections caused by vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-intermediate S. aureus (VISA) strains represent a serious threat to [...] Read more.
The emergence of bacteria resistant to conventional antibiotics is of great concern in modern medicine because it renders ineffectiveness of the current empirical antibiotic therapies. Infections caused by vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-intermediate S. aureus (VISA) strains represent a serious threat to global health due to their considerable morbidity and mortality rates. Therefore, there is an urgent need of research and development of new antimicrobial alternatives against these bacteria. In this context, the use of antimicrobial peptides (AMPs) is considered a promising alternative therapeutic strategy to control resistant strains. Therefore, a wide number of natural, artificial, and synthetic AMPs have been evaluated against VRSA and VISA strains, with great potential for clinical application. In this regard, we aimed to present a comprehensive and systematic review of research findings on AMPs that have shown antibacterial activity against vancomycin-resistant and vancomycin-intermediate resistant strains and clinical isolates of S. aureus, discussing their classification and origin, physicochemical and structural characteristics, and possible action mechanisms. This is the first review that includes all peptides that have shown antibacterial activity against VRSA and VISA strains exclusively. Full article
(This article belongs to the Special Issue Antiviral and Antimicrobial Peptides)
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