Recent Advances in Prevention and Treatment of 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: closed (31 December 2023) | Viewed by 17746

Special Issue Editors


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Guest Editor
Department of Biomedicine and Biotechnology, Faculty of Pharmacy, University of Alcalá, 28871 Alcalá de Henares, Spain
Interests: biofilms; antimicrobial agents; protozoa; fungi; Candida; pathogenicity; drug resistance; combination therapy; mechanism of action; cytotoxicity; in vitro treatments; drug synergism

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Guest Editor
Department of Biomedicine and Biotechnology, Faculty of Pharmacy, University of Alcalá, 28871 Alcalá de Henares, Spain
Interests: fungi; Candida; protozoa; Acanthamoeba; Toxoplasma; pathogenicity; microbicidal agents; biofilms; drug resistance; combination therapy; in vitro susceptibility testing; cytotoxicity; Fractional Inhibitory Concentration (FIC) index; drug synergism

E-Mail Website
Guest Editor
Department of Biomedicine and Biotechnology, Faculty of Pharmacy, University of Alcalá, 28871 Alcalá de Henares, Spain
Interests: fungi; Candida; antifungal agents; biofilms; drug resistance; combination therapy; in vitro susceptibility testing; cytotoxicity; Fractional Inhibitory Concentration (FIC) index; drug synergism

Special Issue Information

Dear Colleagues,

Diseases caused by eukaryotic and prokaryotic microorganisms have a high prevalence and a worldwide distribution, causing millions of deaths every year. However, the antimicrobial agents of choice against some of these infections are limited (e.g., bacteriemia, malaria, candidiasis, leishmaniasis, toxoplasmosis, biofilm-related infections, amebiasis, keratitis, and bloodstream infections). In addition, the majority of therapeutic treatments are associated with microorganism resistance, severe side effects due to toxicity, or limited activity against the causative agent of the  disease.

This Special Issue aims to assemble original research and review articles related to strategies to address the problems associated with these widely distributed infections; new advances in the development of effective strategies to control and treat microbial infections, including new therapeutic treatments, new targets and new diagnosis systems; mechanisms of action; new delivery systems or combined therapy to enhance election treatment efficacy; new formulations to improve tolerability, among others.

Dr. Irene Heredero-Bermejo
Prof. Dr. José Luis Copa Patiño
Dr. Natalia Gómez Casanova
Guest Editors

Manuscript Submission Information

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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
  • opportunistic infections
  • novel treatment
  • diagnosis systems
  • delivery systems
  • resistance
  • tolerability
  • antibacterial
  • biofilm-related infections
  • bacteria
  • antiparasitic
  • protozoa
  • fungi
  • malaria
  • leishmaniasis
  • toxoplasmosis
  • keratitis
  • candidiasis

Published Papers (10 papers)

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Research

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17 pages, 2840 KiB  
Article
Potentiation of Antibiotic Activity of Aztreonam against Metallo-β-Lactamase-Producing Multidrug-Resistant Pseudomonas aeruginosa by 3-O-Substituted Difluoroquercetin Derivatives
by Seongyeon Lee, Taegum Lee, Mi Kyoung Kim, Joong Hoon Ahn, Seri Jeong, Ki-Ho Park and Youhoon Chong
Pharmaceutics 2024, 16(2), 185; https://doi.org/10.3390/pharmaceutics16020185 - 28 Jan 2024
Viewed by 781
Abstract
The combination of aztreonam (ATM) and ceftazidime–avibactam (CAZ-AVI; CZA) has shown therapeutic potential against serine-β-lactamase (SBL)- and metallo-β-lactamase (MBL)-producing Enterobacterales. However, the ability of CZA to restore the antibiotic activity of ATM is severely limited in MBL-producing multidrug-resistant (MDR) Pseudomonas aeruginosa strains [...] Read more.
The combination of aztreonam (ATM) and ceftazidime–avibactam (CAZ-AVI; CZA) has shown therapeutic potential against serine-β-lactamase (SBL)- and metallo-β-lactamase (MBL)-producing Enterobacterales. However, the ability of CZA to restore the antibiotic activity of ATM is severely limited in MBL-producing multidrug-resistant (MDR) Pseudomonas aeruginosa strains because of the myriad of intrinsic and acquired resistance mechanisms associated with this pathogen. We reasoned that the simultaneous inhibition of multiple targets associated with multidrug resistance mechanisms may potentiate the antibiotic activity of ATM against MBL-producing P. aeruginosa. During a search for the multitarget inhibitors through a molecular docking study, we discovered that di-F-Q, the previously reported efflux pump inhibitor of MDR P. aeruginosa, binds to the active sites of the efflux pump (MexB), as well as various β-lactamases, and these sites are open to the 3-O-position of di-F-Q. The 3-O-substituted di-F-Q derivatives were thus synthesized and showed hereto unknown multitarget MDR inhibitory activity against various ATM-hydrolyzing β-lactamases (AmpC, KPC, and New Delhi metallo-β-lactamase (NDM)) and the efflux pump of P. aeruginosa, presumably by forming additional hydrophobic contacts with the targets. The multitarget MDR inhibitor 27 effectively potentiated the antimicrobial activity of ATM and reduced the MIC of ATM more than four-fold in 19 out of 21 MBL-producing P. aeruginosa clinical strains, including the NDM-producing strains which were highly resistant to various combinations of ATM with β-lactamase inhibitors and/or efflux pump inhibitors. Our findings suggest that the simultaneous inhibition of multiple MDR targets might provide new avenues for the discovery of safe and efficient MDR reversal agents which can be used in combination with ATM against MBL-producing MDR P. aeruginosa. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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17 pages, 11690 KiB  
Article
Effectiveness of Nitazoxanide and Electrolyzed Oxiding Water in Treating Chagas Disease in a Canine Model
by Olivia Rodríguez-Morales, Erika Jocelin Mendoza-Téllez, Elizabeth Morales-Salinas and Minerva Arce-Fonseca
Pharmaceutics 2023, 15(5), 1479; https://doi.org/10.3390/pharmaceutics15051479 - 12 May 2023
Cited by 1 | Viewed by 1235
Abstract
Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, and affects seven million people in Latin America. Side effects and the limited efficacy of current treatment have led to new drug research. The objective of this work was to evaluate the [...] Read more.
Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, and affects seven million people in Latin America. Side effects and the limited efficacy of current treatment have led to new drug research. The objective of this work was to evaluate the effectiveness of nitazoxanide (NTZ) and electrolyzed oxidizing water (EOW) in a canine model of experimental CD. Náhuatl dogs were infected with the T. cruzi H8 strain and NTZ- or EOW-treated orally for 10 days. Seronegativity was shown at 12 months post-infection (mpi) in the NTZ-, EOW-, and benznidazole (BNZ)-treated groups. The NTZ and BNZ groups had high levels of IFN-γ, TNF-α, IL-6, IL-12B, and IL-1β at 1.5 mpi and low levels of IL-10. Electrocardiographic studies showed alterations from 3 mpi and worsening at 12 mpi; NTZ treatment produced fewer cardiac pathomorphological changes compared to EOW, similar to BNZ treatment. There was no cardiomegaly in any group. In conclusion, although NTZ and EOW did not prevent changes in cardiac conductivity, they were able to avoid the severity of heart damage in the chronic phase of CD. NTZ induced a favorable proinflammatory immune response after infection, being a better option than EOW as a possible treatment for CD after BNZ. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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19 pages, 4058 KiB  
Article
Molluscicidal and Larvicidal Potency of N-Heterocylic Analogs against Biomophalaria alexandrina Snails and Schistosoma mansoni Larval Stages
by Sherin K. Sheir, Elshaymaa I. Elmongy, Azza H. Mohamad, Gamalat Y. Osman, Shimaa E. Bendary, Abdullah A. S. Ahmed, Reem Binsuwaidan and Ibrahim El-Tantawy El-Sayed
Pharmaceutics 2023, 15(4), 1200; https://doi.org/10.3390/pharmaceutics15041200 - 10 Apr 2023
Viewed by 1393
Abstract
This work describes the synthesis of quinoline-based N--heterocyclic arenes and their biological evaluation as molluscicides against adult Biomophalaria alexandrina snails as well as larvicides against Schistosoma mansoni larvae (miracidia and cercariae). Molecular docking studies were demonstrated to investigate their affinity for cysteine [...] Read more.
This work describes the synthesis of quinoline-based N--heterocyclic arenes and their biological evaluation as molluscicides against adult Biomophalaria alexandrina snails as well as larvicides against Schistosoma mansoni larvae (miracidia and cercariae). Molecular docking studies were demonstrated to investigate their affinity for cysteine protease protein as an interesting target for antiparasitics. Compound AEAN showed the best docking results followed by APAN in comparison to the co-crystallized ligand D1R reflected by their binding affinities and RMSD values. The egg production, hatchability of B. alexandrina snails and ultrastructural topography of S. mansoni cercariae using SEM were assessed. Biological evaluations (hatchability and egg-laying capacity) revealed that the quinoline hydrochloride salt CAAQ was the most effective compound against adult B. alexandrina snails, whereas the indolo-quinoline derivative APAN had the most efficiency against miracidia, and the acridinyl derivative AEAA was the most effective against cercariae and caused 100% mortality. CAAQ and AEAA were found to modulate the biological responses of B. alexandrina snails with/without S. mansoni infection and larval stages that will affect S. mansoni infection. AEAA caused deleterious morphological effects on cercariae. CAAQ caused inhibition in the number of eggs/snail/week and reduced reproductive rate to 43.8% in all the experimental groups. CAAQ and AEAA can be recommended as an effective molluscicide of plant origin for the control program of schistosomiasis. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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30 pages, 946 KiB  
Article
Combined Use of Antimicrobial Peptides with Antiseptics against Multidrug-Resistant Bacteria: Pros and Cons
by Maria S. Zharkova, Aleksey S. Komlev, Tatiana A. Filatenkova, Maria S. Sukhareva, Elizaveta V. Vladimirova, Andrey S. Trulioff, Dmitriy S. Orlov, Alexander V. Dmitriev, Anna G. Afinogenova, Anna A. Spiridonova and Olga V. Shamova
Pharmaceutics 2023, 15(1), 291; https://doi.org/10.3390/pharmaceutics15010291 - 14 Jan 2023
Cited by 1 | Viewed by 2187
Abstract
Antimicrobial peptides (AMPs) are acknowledged as a promising template for designing new antimicrobials. At the same time, existing toxicity issues and limitations in their pharmacokinetics make topical application one of the less complicated routes to put AMPs-based therapeutics into actual medical practice. Antiseptics [...] Read more.
Antimicrobial peptides (AMPs) are acknowledged as a promising template for designing new antimicrobials. At the same time, existing toxicity issues and limitations in their pharmacokinetics make topical application one of the less complicated routes to put AMPs-based therapeutics into actual medical practice. Antiseptics are one of the common components for topical treatment potent against antibiotic-resistant pathogens but often with toxicity limitations of their own. Thus, the interaction of AMPs and antiseptics is an interesting topic that is also less explored than combined action of AMPs and antibiotics. Herein, we analyzed antibacterial, antibiofilm, and cytotoxic activity of combinations of both membranolytic and non-membranolytic AMPs with a number of antiseptic agents. Fractional concentration indices were used as a measure of possible effective concentration reduction achievable due to combined application. Cases of both synergistic and antagonistic interaction with certain antiseptics and surfactants were identified, and trends in the occurrence of these types of interaction were discussed. The data may be of use for AMP-based drug development and suggest that the topic requires further attention for successfully integrating AMPs-based products in the context of complex treatment. AMP/antiseptic combinations show promise for creating topical formulations with improved activity, lowered toxicity, and, presumably, decreased chances of inducing bacterial resistance. However, careful assessment is required to avoid AMP neutralization by certain antiseptic classes in either complex drug design or AMP application alongside other therapeutics/care products. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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12 pages, 1428 KiB  
Article
Inhibition of Candida glabrata Biofilm by Combined Effect of Dendritic Compounds and Amphotericin
by Natalia Gómez-Casanova, Alba Torres-Cano, Alba Xiaohe Elias-Rodriguez, Tania Lozano, Paula Ortega, Rafael Gómez, Jorge Pérez-Serrano, José Luis Copa-Patiño and Irene Heredero-Bermejo
Pharmaceutics 2022, 14(8), 1604; https://doi.org/10.3390/pharmaceutics14081604 - 31 Jul 2022
Cited by 3 | Viewed by 1730
Abstract
In the last decade, Candida glabrata has become an important emerging opportunistic pathogen not only because of the increase in nosocomial infections frequency but also because of its ability to form biofilms and its innate resistance to commercial antifungals. These characteristics make this [...] Read more.
In the last decade, Candida glabrata has become an important emerging opportunistic pathogen not only because of the increase in nosocomial infections frequency but also because of its ability to form biofilms and its innate resistance to commercial antifungals. These characteristics make this pathogen a major problem in hospital settings, including problems regarding equipment, and in immunosuppressed patients, who are at high risk for candidemia. Therefore, there is an urgent need for the development of and search for new antifungal drugs. In this study, the efficacy of two dendritic wedges with 4-phenyl butyric acid (PBA) at the focal point and cationic charges on the surface ArCO2G2(SNMe3I)4 (1) and ArCO2G3(SNMe3I)8 (2) was studied against C. glabrata strain to inhibit the formation of biofilms and eliminate established biofilm. For this, MBIC (minimum biofilm inhibitory concentration), MBDC (minimum biofilm damaging concentrations), as well as MFCB (minimum fungicidal concentration in biofilm) and MBEC (minimum biofilm eradicating concentration) were determined. In addition, different combinations of dendrons and amphotericin B were tested to study possible synergistic effects. On the other hand, cytotoxicity studies were performed. C. glabrata cells and biofilm structure were visualized by confocal microscopy. ArCO2G2(SNMe3I)4 (1) and ArCO2G3(SNMe3I)8 (2) dendrons showed both an MBIC of 8 mg/L and a MBDC of 32 mg/L and 64 mg/L, respectively. These dendrons managed to eradicate the entirety of an established biofilm. In combination with the antifungal amphotericin, it was possible to prevent the generation of biofilms and eradicate established biofilms at lower concentrations than those required individually for each compound at these conditions. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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15 pages, 3572 KiB  
Article
Competitiveness during Dual-Species Biofilm Formation of Fusarium oxysporum and Candida albicans and a Novel Treatment Strategy
by Annarita Falanga, Angela Maione, Alessandra La Pietra, Elisabetta de Alteriis, Stefania Vitale, Rosa Bellavita, Rosa Carotenuto, David Turrà, Stefania Galdiero, Emilia Galdiero and Marco Guida
Pharmaceutics 2022, 14(6), 1167; https://doi.org/10.3390/pharmaceutics14061167 - 30 May 2022
Cited by 13 | Viewed by 2236
Abstract
During an infection, a single or multispecies biofilm can develop. Infections caused by non-dermatophyte molds, such as Fusarium spp. and yeasts, such as Candida spp., are particularly difficult to treat due to the formation of a mixed biofilm of the two species. Fusarium [...] Read more.
During an infection, a single or multispecies biofilm can develop. Infections caused by non-dermatophyte molds, such as Fusarium spp. and yeasts, such as Candida spp., are particularly difficult to treat due to the formation of a mixed biofilm of the two species. Fusarium oxysporum is responsible for approximately 20% of human fusariosis, while Candida albicans is responsible for superficial mucosal and dermal infections and for disseminated bloodstream infections with a mortality rate above 40%. This study aims to investigate the interactions between C. albicans and F. oxysporum dual-species biofilm, considering variable formation conditions. Further, the ability of the WMR peptide, a modified version of myxinidin, to eradicate the mixed biofilm when used alone or in combination with fluconazole (FLC) was tested, and the efficacy of the combination of WMR and FLC at low doses was assessed, as well as its effect on the expression of some biofilm-related adhesin and hyphal regulatory genes. Finally, in order to confirm our findings in vivo and explore the synergistic effect of the two drugs, we utilized the Galleria mellonella infection model. We concluded that C. albicans negatively affects F. oxysporum growth in mixed biofilms. Combinatorial treatment by WMR and FLC significantly reduced the biomass and viability of both species in mature mixed biofilms, and these effects coincided with the reduced expression of biofilm-related genes in both fungi. Our results were confirmed in vivo since the synergistic antifungal activity of WMR and FLC increased the survival of infected larvae and reduced tissue invasion. These findings highlight the importance of drug combinations as an alternative treatment for C. albicans and F. oxysporum mixed biofilms. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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13 pages, 645 KiB  
Article
In Vitro Activity of Ebselen and Diphenyl Diselenide Alone and in Combination with Drugs against Trichophyton mentagrophytes Strains
by Sebastian Gnat, Dominik Łagowski, Mariusz Dyląg, Grzegorz Jóźwiak, Aleksandra Trościańczyk and Aneta Nowakiewicz
Pharmaceutics 2022, 14(6), 1158; https://doi.org/10.3390/pharmaceutics14061158 - 28 May 2022
Cited by 2 | Viewed by 1801
Abstract
Background: Dermatophytoses are one of the most prevalent infectious diseases in the world for which the pace of developing new drugs has not kept pace with the observed therapeutic problems. Thus, searching for new antifungals with an alternative and novel mechanism of action [...] Read more.
Background: Dermatophytoses are one of the most prevalent infectious diseases in the world for which the pace of developing new drugs has not kept pace with the observed therapeutic problems. Thus, searching for new antifungals with an alternative and novel mechanism of action is necessary. Objective: This study aimed to evaluate the antifungal activity of ebselen and diphenyl diselenide against Trichophyton mentagrophytes clinical isolates. Methods: In vitro antifungal susceptibility was assessed for organoselenium compounds used alone or in combination with allylamines and azoles according to the 3rd edition of the CLSI M38 protocol. Results: Ebselen demonstrated high antifungal activity with MICGM equal to 0.442 μg/mL and 0.518 μg/mL in the case of human and animal origin strains, respectively. The values of MICGM of diphenyl diselenide were higher: 17.36 μg/mL and 13.45 μg/mL for the human and animal isolates, respectively. Synergistic or additive effects between terbinafine and ebselen or diphenyl diselenide were observed in the case of 12% and 20% strains, respectively. In turn, the combination of itraconazole with diphenyl diselenide showed a synergistic effect only in the case of 6% of the tested strains, whereas no synergism was shown in the combination with ebselen. Conclusions: The results highlight the promising activity of organoselenium compounds against Trichophyton mentagrophytes. However, their use in combinational therapy with antifungal drugs seems to be unjustified due to the weak synergistic effect observed. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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10 pages, 526 KiB  
Article
Prevalence of Mutations in the pfcoronin Gene and Association with Ex Vivo Susceptibility to Common Quinoline Drugs against Plasmodium falciparum
by Océane Delandre, Mathieu Gendrot, Isabelle Fonta, Joel Mosnier, Nicolas Benoit, Rémy Amalvict, Nicolas Gomez, Marylin Madamet and Bruno Pradines
Pharmaceutics 2021, 13(8), 1273; https://doi.org/10.3390/pharmaceutics13081273 - 17 Aug 2021
Cited by 3 | Viewed by 1794
Abstract
Background: Artemisinin-based combination therapy (ACT) was recommended to treat uncomplicated falciparum malaria. Unlike the situation in Asia where resistance to ACT has been reported, artemisinin resistance has not yet emerged in Africa. However, some rare failures with ACT or patients continuing to be [...] Read more.
Background: Artemisinin-based combination therapy (ACT) was recommended to treat uncomplicated falciparum malaria. Unlike the situation in Asia where resistance to ACT has been reported, artemisinin resistance has not yet emerged in Africa. However, some rare failures with ACT or patients continuing to be parasitaemic on day 3 after ACT treatment have been reported in Africa or in travellers returning from Africa. Three mutations (G50E, R100K, and E107V) in the pfcoronin gene could be responsible for artemisinin resistance in Africa. Methods: The aims of this study were first to determine the prevalence of mutations in the pfcoronin gene in African P. falciparum isolates by Sanger sequencing, by targeting the 874 samples collected from patients hospitalised in France after returning from endemic areas in Africa between 2018 and 2019, and secondly to evaluate their association with in vitro reduced susceptibility to standard quinoline antimalarial drugs, including chloroquine, quinine, mefloquine, desethylamodiaquine, lumefantrine, piperaquine, and pyronaridine. Results: The three mutations in the pfcoronin gene (50E, 100K, and 107V) were not detected in the 874 P. falciparum isolates. Current data show that another polymorphism (P76S) is present in many countries of West Africa (mean prevalence of 20.7%) and Central Africa (11.9%) and, rarely, in East Africa (4.2%). This mutation does not appear to be predictive of in vitro reduced susceptibility to quinolines, including artemisinin derivative partners in ACT such as amodiaquine, lumefantrine, piperaquine, pyronaridine, and mefloquine. Another mutation (V62M) was identified at low prevalence (overall prevalence of 1%). Conclusions: The 76S mutation is present in many African countries with a prevalence above 10%. It is reassuring that this mutation does not confer in vitro resistance to ACT partners. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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Review

Jump to: Research

17 pages, 2732 KiB  
Review
The Design, Synthesis and Mechanism of Action of Paxlovid, a Protease Inhibitor Drug Combination for the Treatment of COVID-19
by Miklós Bege and Anikó Borbás
Pharmaceutics 2024, 16(2), 217; https://doi.org/10.3390/pharmaceutics16020217 - 02 Feb 2024
Viewed by 1276
Abstract
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an enormous challenge to health care systems and medicine. As a result of global research efforts aimed at preventing and effectively treating SARS-CoV-2 infection, vaccines with fundamentally new mechanisms [...] Read more.
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an enormous challenge to health care systems and medicine. As a result of global research efforts aimed at preventing and effectively treating SARS-CoV-2 infection, vaccines with fundamentally new mechanisms of action and some small-molecule antiviral drugs targeting key proteins in the viral cycle have been developed. The most effective small-molecule drug approved to date for the treatment of COVID-19 is PaxlovidTM, which is a combination of two protease inhibitors, nirmatrelvir and ritonavir. Nirmatrelvir is a reversible covalent peptidomimetic inhibitor of the main protease (Mpro) of SARS-CoV-2, which enzyme plays a crucial role in viral reproduction. In this combination, ritonavir serves as a pharmacokinetic enhancer, it irreversibly inhibits the cytochrome CYP3A4 enzyme responsible for the rapid metabolism of nirmatrelvir, thereby increasing the half-life and bioavailability of nirmatrelvir. In this tutorial review, we summarize the development and pharmaceutical chemistry aspects of Paxlovid, covering the evolution of protease inhibitors, the warhead design, synthesis and the mechanism of action of nirmatrelvir, as well as the synthesis of ritonavir and its CYP3A4 inhibition mechanism. The efficacy of Paxlovid to novel virus mutants is also overviewed. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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13 pages, 291 KiB  
Review
Intrastromal Injections in the Management of Infectious Keratitis
by Mihail Zemba, Madalina Radu, Sinziana Istrate, Otilia-Maria Dumitrescu, Mihai Alexandru Ionescu, Andrei Vatafu and Ileana Ramona Barac
Pharmaceutics 2023, 15(4), 1091; https://doi.org/10.3390/pharmaceutics15041091 - 29 Mar 2023
Cited by 1 | Viewed by 1828
Abstract
Infectious keratitis is a major global cause of vision loss and blindness. Prompt diagnosis and targeted antibiotic treatment are crucial for managing the condition. Topical antimicrobials are the most effective therapy for bacterial keratitis, but they can lead to unsatisfactory results due to [...] Read more.
Infectious keratitis is a major global cause of vision loss and blindness. Prompt diagnosis and targeted antibiotic treatment are crucial for managing the condition. Topical antimicrobials are the most effective therapy for bacterial keratitis, but they can lead to unsatisfactory results due to ocular perforation, scarring, and melting. Intrastromal injection is a newer technique for delivering antimicrobials directly to the site of infection and has been successful in treating severe, treatment-resistant infectious keratitis, especially when surgery is not recommended. In cases where deep stromal disease is resistant to topical treatment, intrastromal antimicrobial injections may be necessary to achieve higher drug concentration at the infection site. However, the use of intrastromal antibiotics is limited, as topical antibacterial agents have better penetration than antifungal agents. Bacterial and fungal keratitis have been extensively researched for intrastromal medication injections, while there is limited evidence for viral keratitis. This review emphasizes the potential of intrastromal antimicrobial injections as an alternative for managing severe refractory infectious keratitis. The technique offers direct targeting of the infection site and faster resolution in some cases compared to topical therapy. However, further research is needed to determine the safest antimicrobials options, minimal effective doses, and concentrations for various pathogens. Intrastromal injections may serve as a non-surgical treatment option in high-risk cases, with benefits including direct drug delivery and reduced epithelial toxicity. Despite promising findings, more studies are required to confirm the safety and efficacy of this approach. Full article
(This article belongs to the Special Issue Recent Advances in Prevention and Treatment of Infectious Diseases)
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