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New Horizons in Antiviral and Antibacterial Agent Discovery
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New Horizons in Antiviral and Antibacterial Agent Discovery

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 November 2025) | Viewed by 3631

Special Issue Editors

Dr. Federica Dell’Annunziata

E-Mail Website
Guest Editor
Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
Interests: antibiotic resistance mechanisms; host–pathogen interactions; multidrug-resistant bacterial infections; novel antibacterial compounds; antiviral mechanisms and therapeutics; antimi-crobial compound–membrane interactions; nanomaterials in microbial pathogenesis; target identification for antimicrobial drug development
Special Issues, Collections and Topics in MDPI journals
Dr. Veronica Folliero

E-Mail Website
Guest Editor
Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
Interests: antibiotic resistance mechanisms; host–pathogen interactions; multidrug-resistant bacterial infections; novel antibacterial compounds; antiviral mechanisms and therapeutics; antimi-crobial compound–membrane interactions; nanomaterials in microbial pathogenesis; target identification for antimicrobial drug development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The prevalence of antimicrobial-resistant bacteria and viruses poses a major threat to global public health and constitutes a silent pandemic. Multidrug-resistant (MDR) strains compromise the effectiveness of conventional therapies, making infections difficult to treat and leading to a risk of complications and mortality.The World Health Organization emphasizes the urgent need to invest in the development of new drugs and alternative therapeutic strategies. Given this scenario, the Special Issue “New Horizons in Antiviral and Antibacterial Agent Discovery” aims to collect scientific contributions to explore new frontiers in the fight against MDR minfections. The Special Issue focuses on innovative approaches for the identification and development of antiviral and antibacterial agents, with particular attention to the following:

  • Natural compounds, derived from sustainable extraction methods or green synthesis techniques, which represent a valuable and underutilized resource;
  • Synthetic molecules, rationally designed to overcome resistance mechanisms or to target novel biological pathways;
  • Repurposed drugs, already approved by the Food and Drug Administration for other therapeutic indications, but with potential antimicrobial activity to be rediscovered;
  • Innovative pharmacological strategies, including combination therapies, aimed at counteracting the spread of increasingly difficult-to-treat pathogens.

We invite the scientific community to contribute original research articles and reviews to this multidisciplinary Special Issue.

We would like to acknowledge Dr. Flora Salzano (Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy) for her participation as Guest Editor Assistant in the development of this Special Issue.

Dr. Federica Dell’Annunziata
Dr. Veronica Folliero
Guest Editors

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antimicrobial resistance
  • multidrug-resistant infections
  • new antimicrobial drug development
  • natural and synthetic an-timicrobial agents
  • drug repurposing

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

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Research

13 pages, 1462 KB  
Article
Hyaluronic Acid-Palmitate Nanoparticle Delivery of Carbonic Anhydrase Inhibitors Impairs Growth and Early Metabolism in Escherichia coli Through β- and γ-Carbonic Anhydrase-Associated Processes
by Viviana De Luca, Valentina Verdoliva, Claudiu T. Supuran, Stefania De Luca and Clemente Capasso
Int. J. Mol. Sci. 2026, 27(2), 621; https://doi.org/10.3390/ijms27020621 - 7 Jan 2026
Viewed by 742
Abstract
Bacterial carbonic anhydrases (CAs) are essential for intracellular pH regulation, bicarbonate homeostasis, and energy metabolism, making them attractive antimicrobial targets. Here, building on evidence that acetazolamide (AZA) delivered via hyaluronic acid–palmitate (HA-PA) nanocarriers impairs Escherichia coli growth and its glucose uptake, we investigated [...] Read more.
Bacterial carbonic anhydrases (CAs) are essential for intracellular pH regulation, bicarbonate homeostasis, and energy metabolism, making them attractive antimicrobial targets. Here, building on evidence that acetazolamide (AZA) delivered via hyaluronic acid–palmitate (HA-PA) nanocarriers impairs Escherichia coli growth and its glucose uptake, we investigated the physiological roles of β- and γ-class CAs using sulphonamide inhibitors with distinct selectivity encapsulated in HA-PA nanomicelles to ensure intracellular delivery. AZA, a potent dual β/γ-CA inhibitor, ethoxzolamide (EZA), a selective β-CA inhibitor, and hydrochlorothiazide (HCT), a weaker inhibitor of both classes, were tested for effects on bacterial physiology. The nanoparticles reduced growth in a dose- and class-dependent manner, with AZA exerting the strongest activity, EZA intermediate inhibition, and HCT only modest effects at higher concentrations. Early metabolic responses assessed via intracellular ATP after three hours of exposure revealed an unexpected and reproducible ATP increase for all inhibitors relative to untreated cells, suggesting reduced ATP consumption in bicarbonate-dependent pathways. These findings provide indirect yet compelling evidence that β- and γ-class CAs influence bacterial energy homeostasis and support the rationale for CA inhibition as an antimicrobial strategy, while highlighting HA-PA carriers as effective systems for delivering CA inhibitors intracellularly and enhancing their functional activity in bacterial cells. Full article
(This article belongs to the Special Issue New Horizons in Antiviral and Antibacterial Agent Discovery)
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21 pages, 4174 KB  
Article
Identification of Novel TAT-I24-Related Peptides with Antiviral Activities
by Hanna Harant, Siegfried Höfinger, Reingard Grabherr, Zsolt Ruzsics and Hartmut Hengel
Int. J. Mol. Sci. 2025, 26(23), 11433; https://doi.org/10.3390/ijms262311433 - 26 Nov 2025
Viewed by 2576
Abstract
To identify novel peptides with potential antiviral activities, a database search was performed based on the primary sequence of the peptide I24 (CLAFYACFC), the effective part of the antiviral peptide TAT-I24 consisting of peptide I24 and the cell penetrating TAT-peptide (amino-acids 48–60; GRKKRRQRRRPPQ). [...] Read more.
To identify novel peptides with potential antiviral activities, a database search was performed based on the primary sequence of the peptide I24 (CLAFYACFC), the effective part of the antiviral peptide TAT-I24 consisting of peptide I24 and the cell penetrating TAT-peptide (amino-acids 48–60; GRKKRRQRRRPPQ). A Protein BLAST search identified several sequences with high similarity to I24 in diverse proteins, some of which are known to be involved in the interaction with nucleic acids. Selected sequences and newly designed variants of I24 were synthesized as TAT fusion peptides and tested for antiviral activity in two well-established models: baculovirus transduction of HEK293 cells and mouse cytomegalovirus (MCMV) infection of NIH/3T3 cells. Several of the TAT-fusion peptides exhibited antiviral activities with a potency comparable to TAT-I24. The ability of these peptides to bind double-stranded DNA suggested the same mode of action. Several peptides caused swelling of red blood cells (RBC) but with only one peptide clearly inducing haemolysis. With two exceptions, RBC swelling was observed with antivirally active peptides but not with less active peptides, indicating that antiviral activities are linked to an effect on membrane integrity of target cells. Structural prediction of the TAT-fusion peptides indicated formation of two α-helical elements, with several of these peptides showing remarkable similarity when subjected to structural alignment. Full article
(This article belongs to the Special Issue New Horizons in Antiviral and Antibacterial Agent Discovery)
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