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Pharmaceutics
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Novel Drugs, Targets and Therapies Against Infectious Diseases
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Novel Drugs, Targets and Therapies Against Infectious Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 12750

Special Issue Editors

Dr. Eva Torres-Sangiao

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Guest Editor
Clinical Microbiology Laboratory, University Hospital Marqués de Valdecilla, Researh Institute IDIVAL, 39001 Santander, Spain
Interests: system biology; immunoproteome; infectious diseases; sexual transmission diseases; mass spectrometry
Special Issues, Collections and Topics in MDPI journals
Dr. Erkko O. Ylösmäki

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Guest Editor
1. Director, Research and Development Rokote Laboratories Finland Oy, 00014 Helsinki, Finland
2. Adjunct Professor, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland
Interests: cancer vaccines; vaccines for infectious diseases; cancer immunotherapy; oncolytic viruses; phage display; adenovirus; vaccinia; therapeutic antibodies

Special Issue Information

Dear Colleagues,

Currently, the treatment of infectious diseases has become substantially complicated and is therefore a serious problem in health and disease management. The increase in drug resistance, as well as the threat of new pandemics and emerging infections is a fact. This necessitates the development of new strategies, improved conventional antimicrobials drugs, or even completely new mechanisms of action.

The discovery of new compounds as candidates and the development of new strategies are essential scientifically, socially, and economically. On the other hand, improvements in bioinformatics and computational biology have increased the efficiency of many stages of the drug discovery pipeline or strategies. In fact, bioinformatics methods such as molecular dynamics, molecular docking or QSAR (including in silico methods) are strategically used when new drugs are considered for potential use, e.g., for SARS-CoV-2 infection.

This Special Issue on “Novel Drugs, Targets, and Therapies against Infectious Diseases” focuses on the identification and further optimization of corresponding compounds and strategies, for example, i) target-, ligand-, and computer-based approaches that involve biological evaluation, ii) drug design and drug formulation/delivery, and iii) molecular docking, molecular dynamics. Interdisciplinary studies are encouraged for submission.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Phagotherapy;
  • Biological therapies, including peptides and antibodies;
  • Optimization of pipelines for personalized diagnosis;
  • Vaccines;
  • Bioinformatic approaches;
  • Drug formulation/delivery and targeted therapy;
  • New therapies and strategies to tackle resistance, infections, and oncolytic virus.

We look forward to receiving your contributions.

Dr. Eva Torres-Sangiao
Dr. Erkko O. Ylösmäki
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 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 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. Pharmaceutics 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 2900 CHF (Swiss Francs). 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

  • infectious diseases
  • immunotherapy
  • vaccines
  • nanotechnology
  • drug formulation
  • targets
  • biological therapies

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Published Papers (7 papers)

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12 pages, 1341 KiB  
Article
Multidrug Combinations against SARS-CoV-2 Using GS-441524 or Ivermectin with Molnupiravir and/or Nirmatrelvir in Reconstituted Human Nasal Airway Epithelia
by Denise Siegrist, Hulda R. Jonsdottir, Mendy Bouveret, Bernadett Boda, Samuel Constant and Olivier B. Engler
Pharmaceutics 2024, 16(10), 1262; https://doi.org/10.3390/pharmaceutics16101262 - 27 Sep 2024
Viewed by 854
Abstract
Background. The emergence, global spread, and persistence of SARS-CoV-2 resulted in an unprecedented need for effective antiviral drugs. Throughout the pandemic, various drug development and treatment strategies were adopted, including repurposing of antivirals designed for other viruses along with a multitude of other [...] Read more.
Background. The emergence, global spread, and persistence of SARS-CoV-2 resulted in an unprecedented need for effective antiviral drugs. Throughout the pandemic, various drug development and treatment strategies were adopted, including repurposing of antivirals designed for other viruses along with a multitude of other drugs with varying mechanisms of action (MoAs). Furthermore, multidrug treatment against COVID-19 is an ongoing topic and merits further investigation. Method/Objectives. We assessed the efficacy of multidrug treatment against SARS-CoV-2 in reconstituted human nasal epithelia, using combinations of molnupiravir and nirmatrelvir as a baseline, adding suboptimal concentrations of either GS-441524 or ivermectin, attempting to increase overall antiviral activity while lowering the overall therapeutic dose. Results. Nirmatrelvir combined with molnupiravir, GS-441524, or ivermectin at suboptimal concentrations show increased antiviral activity compared to single treatment. No triple combinations showed improved inhibition of SARS-CoV-2 replication beyond what was observed for double treatments. Conclusions. In general, we observed that the addition of a third compound is not beneficial for antiviral activity, while various double combinations exhibit increased antiviral activity over single treatment. Full article
(This article belongs to the Special Issue Novel Drugs, Targets and Therapies Against Infectious Diseases)
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16 pages, 4622 KiB  
Article
The Potential of Dutasteride for Treating Multidrug-Resistant Candida auris Infection
by J. Francis Borgio, Noor B. Almandil, Prathas Selvaraj, J. Sherlin John, Rahaf Alquwaie, Eman AlHasani, Norah F. Alhur, Razan Aldahhan, Reem AlJindan, Dana Almohazey, Sarah Almofty, T. Stalin Dhas and Sayed AbdulAzeez
Pharmaceutics 2024, 16(6), 810; https://doi.org/10.3390/pharmaceutics16060810 - 14 Jun 2024
Cited by 1 | Viewed by 1484
Abstract
Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen Candida auris. In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti- [...] Read more.
Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen Candida auris. In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti-C. auris activity. High-throughput virtual screening of 1,3-beta-glucanosyltransferase inhibitors was conducted, followed by an analysis of the stability of 1,3-beta-glucanosyltransferase drug complexes and 1,3-beta-glucanosyltransferase–dutasteride metabolite interactions and the confirmation of their activity in biofilm formation and planktonic growth. The analysis identified dutasteride, a drug with no prior antifungal indications, as a potential medication for anti-auris activity in seven clinical C. auris isolates from Saudi Arabian patients. Dutasteride was effective at inhibiting biofilm formation by C. auris while also causing a significant reduction in planktonic growth. Dutasteride treatment resulted in disruption of the cell membrane, the lysis of cells, and crushed surfaces on C. auris, and significant (p-value = 0.0057) shrinkage in the length of C. auris was noted at 100,000×. In conclusion, the use of repurposed dutasteride with anti-C. auris potential can enable rapid recovery in patients with difficult-to-treat candidiasis caused by C. auris and reduce the transmission of nosocomial infection. Full article
(This article belongs to the Special Issue Novel Drugs, Targets and Therapies Against Infectious Diseases)
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27 pages, 6444 KiB  
Article
Silversol® (a Colloidal Nanosilver Formulation) Inhibits Growth of Antibiotic-Resistant Staphylococcus aureus by Disrupting Its Physiology in Multiple Ways
by Nidhi Thakkar, Gemini Gajera, Dilip Mehta and Vijay Kothari
Pharmaceutics 2024, 16(6), 726; https://doi.org/10.3390/pharmaceutics16060726 - 28 May 2024
Viewed by 1214
Abstract
Antibiotic-resistant strains of Staphylococcus aureus are being viewed as a serious threat by various public health agencies. Identifying novel targets in this important pathogen is crucial to the development of new effective antibacterial formulations. We investigated the antibacterial effect of a colloidal nanosilver [...] Read more.
Antibiotic-resistant strains of Staphylococcus aureus are being viewed as a serious threat by various public health agencies. Identifying novel targets in this important pathogen is crucial to the development of new effective antibacterial formulations. We investigated the antibacterial effect of a colloidal nanosilver formulation, Silversol®, against an antibiotic-resistant strain of S. aureus using appropriate in vitro assays. Moreover, we deciphered the molecular mechanisms underlying this formulation’s anti-S. aureus activity using whole transcriptome analysis. Lower concentrations of the test formulation exerted a bacteriostatic effect against this pathogen, and higher concentrations exerted a bactericidal effect. Silversol® at sub-lethal concentration was found to disturb multiple physiological traits of S. aureus such as growth, antibiotic susceptibility, membrane permeability, efflux, protein synthesis and export, biofilm and exopolysaccharide production, etc. Transcriptome data revealed that the genes coding for transcriptional regulators, efflux machinery, transferases, β-lactam resistance, oxidoreductases, metal homeostasis, virulence factors, and arginine biosynthesis are expressed differently under the influence of the test formulation. Genes (argG and argH) involved in arginine biosynthesis emerged among the major targets of Silversol®’s antibacterial activity against S. aureus. Full article
(This article belongs to the Special Issue Novel Drugs, Targets and Therapies Against Infectious Diseases)
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20 pages, 4615 KiB  
Article
Synergistic Activity and Mechanism of Sanguinarine with Polymyxin B against Gram-Negative Bacterial Infections
by Luyao Qiao, Yu Zhang, Ying Chen, Xiangyin Chi, Jinwen Ding, Hongjuan Zhang, Yanxing Han, Bo Zhang, Jiandong Jiang and Yuan Lin
Pharmaceutics 2024, 16(1), 70; https://doi.org/10.3390/pharmaceutics16010070 - 3 Jan 2024
Cited by 1 | Viewed by 1847
Abstract
Compounds that potentiate the activity of clinically available antibiotics provide a complementary solution, except for developing novel antibiotics for the rapid emergence of multidrug-resistant Gram-negative bacteria (GNB). We sought to identify compounds potentiating polymyxin B (PMB), a traditional drug that has been revived [...] Read more.
Compounds that potentiate the activity of clinically available antibiotics provide a complementary solution, except for developing novel antibiotics for the rapid emergence of multidrug-resistant Gram-negative bacteria (GNB). We sought to identify compounds potentiating polymyxin B (PMB), a traditional drug that has been revived as the last line for treating life-threatening GNB infections, thus reducing its nephrotoxicity and heterogeneous resistance in clinical use. In this study, we found a natural product, sanguinarine (SA), which potentiated the efficacy of PMB against GNB infections. The synergistic effect of SA with PMB was evaluated using a checkerboard assay and time–kill curves in vivo and the murine peritonitis model induced by Escherichia coli in female CD-1 mice in vivo. SA assisted PMB in accelerating the reduction in bacterial loads both in vitro and in vivo, improving the inflammatory responses and survival rate of infected animals. The subsequent detection of the intracellular ATP levels, membrane potential, and membrane integrity indicated that SA enhanced the bacterial-membrane-breaking capacity of PMB. A metabolomic analysis showed that the inhibition of energy metabolism, interference with nucleic acid biosynthesis, and the blocking of L-Ara4N-related PMB resistance may also contribute to the synergistic effect. This study is the first to reveal the synergistic activity and mechanism of SA with PMB, which highlights further insights into anti-GNB drug development. Full article
(This article belongs to the Special Issue Novel Drugs, Targets and Therapies Against Infectious Diseases)
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20 pages, 1445 KiB  
Article
Preclinical Study in Mouse Thymus and Thymocytes: Effects of Treatment with a Combination of Sodium Dichloroacetate and Sodium Valproate on Infectious Inflammation Pathways
by Donatas Stakišaitis, Linas Kapočius, Evelina Kilimaitė, Dovydas Gečys, Lina Šlekienė, Ingrida Balnytė, Jolita Palubinskienė and Vaiva Lesauskaitė
Pharmaceutics 2023, 15(12), 2715; https://doi.org/10.3390/pharmaceutics15122715 - 30 Nov 2023
Cited by 3 | Viewed by 1624
Abstract
The research presents data from a preclinical study on the anti-inflammatory effects of a sodium dichloroacetate and sodium valproate combination (DCA–VPA). The 2-week treatment with a DCA 100 mg/kg/day and VPA 150 mg/kg/day combination solution in drinking water’s effects on the thymus weight, [...] Read more.
The research presents data from a preclinical study on the anti-inflammatory effects of a sodium dichloroacetate and sodium valproate combination (DCA–VPA). The 2-week treatment with a DCA 100 mg/kg/day and VPA 150 mg/kg/day combination solution in drinking water’s effects on the thymus weight, its cortex/medulla ratio, Hassall’s corpuscles (HCs) number in the thymus medulla, and the expression of inflammatory and immune-response-related genes in thymocytes of male Balb/c mice were studied. Two groups of mice aged 6–7 weeks were investigated: a control (n = 12) and a DCA–VPA-treated group (n = 12). The treatment did not affect the body weight gain (p > 0.05), the thymus weight (p > 0.05), the cortical/medulla ratio (p > 0.05), or the number of HCs (p > 0.05). Treatment significantly increased the Slc5a8 gene expression by 2.1-fold (p < 0.05). Gene sequence analysis revealed a significant effect on the expression of inflammation-related genes in thymocytes by significantly altering the expression of several genes related to the cytokine activity pathway, the inflammatory response pathway, and the Il17 signaling pathway in thymocytes. Data suggest that DCA–VPA exerts an anti-inflammatory effect by inhibiting the inflammatory mechanisms in the mouse thymocytes. Full article
(This article belongs to the Special Issue Novel Drugs, Targets and Therapies Against Infectious Diseases)
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14 pages, 302 KiB  
Article
Stability Studies of Antipseudomonal Beta Lactam Agents for Outpatient Therapy
by Beatriz Fernández-Rubio, Laura Herrera-Hidalgo, Arístides de Alarcón, Rafael Luque-Márquez, Luis E. López-Cortés, Sònia Luque, José María Gutiérrez-Urbón, Aurora Fernández-Polo, Alicia Gutiérrez-Valencia and María V. Gil-Navarro
Pharmaceutics 2023, 15(12), 2705; https://doi.org/10.3390/pharmaceutics15122705 - 30 Nov 2023
Cited by 2 | Viewed by 2077
Abstract
Outpatient parenteral antimicrobial therapy (OPAT) is a useful treatment strategy against Pseudomonas aeruginosa and other multidrug-resistant bacteria. However, it is hindered by the lack of stability data for the administration of antibiotics under OPAT conditions. Our objective was to investigate the stability of [...] Read more.
Outpatient parenteral antimicrobial therapy (OPAT) is a useful treatment strategy against Pseudomonas aeruginosa and other multidrug-resistant bacteria. However, it is hindered by the lack of stability data for the administration of antibiotics under OPAT conditions. Our objective was to investigate the stability of nine antipseudomonal and broad-spectrum beta lactam antibiotics (aztreonam, cefepime, cefiderocol, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, meropenem/vaborbactam, and piperacillin/tazobactam) to allow the spread of OPAT programs. All the antibiotics were diluted in 500 mL 0.9% sodium chloride and stored at 4, 25, 32, and 37 °C for 72 h in two different devices (infusion bags and elastomeric pumps). The solutions were considered stable if the color, clearness, and pH remained unchanged and if the percentage of intact drug was ≥90%. All the antimicrobials remained stable 72 h under refrigerated conditions and at least 30 h at 25 °C. At 32 °C, all the antibiotics except for meropenem and meropenem/vaborbactam remained stable for 24 h or more. At 37 °C, only aztreonam, piperacillin/tazobactam, cefepime, cefiderocol, and ceftolozane/tazobactam were stable for at least 24 h. The stability results were the same in the two devices tested. All the antibiotics studied are actual alternatives for the treatment of antipseudomonal or multidrug-resistant infections in OPAT programs, although the temperature of the devices is crucial to ensure antibiotic stability. Full article
(This article belongs to the Special Issue Novel Drugs, Targets and Therapies Against Infectious Diseases)
14 pages, 1519 KiB  
Article
Ampicillin Stability in a Portable Elastomeric Infusion Pump: A Step Forward in Outpatient Parenteral Antimicrobial Therapy
by Lorena Rodríguez-Martínez, Ana Castro-Balado, Gonzalo Hermelo-Vidal, Enrique Bandín-Vilar, Iria Varela-Rey, Francisco José Toja-Camba, Teresa Rodríguez-Jato, Ignacio Novo-Veleiro, Pablo Manuel Varela-García, Irene Zarra-Ferro, Miguel González-Barcia, Cristina Mondelo-García, Jesús Mateos and Anxo Fernández-Ferreiro
Pharmaceutics 2023, 15(8), 2099; https://doi.org/10.3390/pharmaceutics15082099 - 8 Aug 2023
Cited by 1 | Viewed by 2745
Abstract
Outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion pumps is postulated as a very promising solution to treat complicated infections, such as endocarditis or osteomyelitis, that require patients to stay in hospital during extended periods of time, thus reducing their quality of life [...] Read more.
Outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion pumps is postulated as a very promising solution to treat complicated infections, such as endocarditis or osteomyelitis, that require patients to stay in hospital during extended periods of time, thus reducing their quality of life and increasing the risk of complications. However, stability studies of drugs in elastomeric devices are scarce, which limits their use in OPAT. Therefore, we evaluated the stability of ampicillin in sodium chloride 0.9% at two different concentrations, 50 and 15 mg/mL, in an elastomeric infusion pump when stored in the refrigerator and subsequently in real-life conditions at two different temperatures, 25 and 32 °C, with and without the use of a cooling device. The 15 mg/mL ampicillin is stable for up to 72 h under refrigeration, allowing subsequent dosing at 25 °C for 24 h with and without a cooling device, but at 32 °C its concentration drops below 90% after 8 h. In contrast, 50 mg/mL ampicillin only remains stable for the first 24 h under refrigeration, and subsequent administration at room temperature is not possible, even with the use of a cooling system. Our data support that 15 mg/mL AMP is suitable for use in OPAT if the volume and rate of infusion are tailored to the dosage needs of antimicrobial treatments. Full article
(This article belongs to the Special Issue Novel Drugs, Targets and Therapies Against Infectious Diseases)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Ampicillin Stability in a Portable Elastomeric Infusion Pump, a Step Forward in Outpatient Parenteral Antimicrobial Therapy
Author: Mateos
Highlights: -The results show a stability of up to 72 h under refrigeration of 15 mg/mL AMP, ensuring a subsequent administration at room temperature for 24 hours. -50 mg/mL AMP can only be cold-storaged for 24 h and administered in the subsequent 8 hours. -The present study clearly positions OPAT as a new feasible option for patients.

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