Drug Discovery for Infectious Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 21812

Special Issue Editors

1. E-Group ICT SOFTWARE, H-1027 Budapest, Hungary
2. Department of Organic Chemistry, Semmelweis University, H-1092 Budapest, Hungary
Interests: medicinal chemistry; drug discovery strategies; drug design; multiple targeting
1. Department of Pharmacology and Toxicology, University of Veterinary Medicine, István utca 2, H-1078 Budapest, Hungary
2. National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine, István utca 2, H-1078 Budapest, Hungary
Interests: pharmacology; drug repositioning; pharmacokinetics; antimicrobial resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infectious diseases encompass a wide range of diseases caused by viruses, bacteria, fungi and parasites, all of which have serious consequences for human health. The rapid emergence of new viral and parasitic diseases, as well as the spread of antimicrobial resistance, is also putting drug research at a disadvantage, posing a challenge to the biomedical research field to develop new drugs and drug innovation strategies to keep pace with these new needs. Recent pandemics in particular highlight the need for novel antiviral drugs in several areas of human and animal health.

This Special Issue welcomes reviews and papers describing host-entry and reproduction of the pathogen and pathomechanism of diseases at the molecular level, as well as those reporting on the discovery of new drug candidates that affect these processes. New mechanisms of drug action and new drug targets are especially promising approaches, which, besides their significance, may have potential applications in other areas. Approaches based on the ‘One Health’ principle are also encouraged. Innovative drug discovery strategies, including repositioning strategies from other pharmacological areas, drug combinations or multiple-targeting ligands, as well as new drug formulations for improved ADME, also represent suitable subjects of submitted papers.

Prof. Dr. Péter Mátyus
Dr. Ákos Jerzsele
Guest Editors

Manuscript Submission Information

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Keywords

  • human drug discovery
  • antiviral, antibacterial, antifungal, antiparasitic
  • infectious pathomechanisms
  • drug discovery strategy
  • one health principle

Published Papers (11 papers)

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Research

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15 pages, 4268 KiB  
Article
Design of a Novel and Potent Multi-Epitope Chimeric Vaccine against Human Papillomavirus (HPV): An Immunoinformatics Approach
by Muhammad Shahab, Dejia Guo, Guojun Zheng and Yening Zou
Biomedicines 2023, 11(5), 1493; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11051493 - 22 May 2023
Cited by 2 | Viewed by 1593
Abstract
In the current era, our experience is full of pandemic infectious agents that no longer threaten the major local source but the whole globe. One such infectious agent is HPV, a sexually transmitted disease that can cause various clinical disorders, including benign lesions [...] Read more.
In the current era, our experience is full of pandemic infectious agents that no longer threaten the major local source but the whole globe. One such infectious agent is HPV, a sexually transmitted disease that can cause various clinical disorders, including benign lesions and cervical cancer. Since available vaccines still need further improvements in order to enhance efficacy, our goal was to design a chimeric vaccine against HPV using an immunoinformatics approach. For designing the vaccine, the sequence of HPV was retrieved, and then phylogenetic analysis was performed. Several CTL epitopes, HTL epitopes, and LBL epitopes were all predicted using bioinformatics tools. After checking the antigenicity, allergenicity, and toxicity scores, the best epitopes were selected for vaccine construction, and then physicochemical and immunological properties were analyzed. Subsequently, vaccine 3D structure prediction, refinement, and validation were performed. Molecular docking and dynamics simulation techniques were used to explore the interactions between the Toll-like receptor 2 and the modeled vaccine construct. To ensure the vaccine protein was expressed at a higher level, the construct was computationally cloned into the pET28a (+) plasmid. The molecular docking and simulation results showed that our designed vaccine is stable, of immunogenic quality, and has considerable solubility. Through in silico immune simulation, it was predicted that the designed polypeptide vaccine construct would trigger both humoral and cellular immune responses. The developed vaccine showed significant affinity for the TLR2 receptor molecule. However, additional laboratory research is required to evaluate its safety and efficacy. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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18 pages, 5639 KiB  
Article
In Silico Identification of Lead Compounds for Pseudomonas Aeruginosa PqsA Enzyme: Computational Study to Block Biofilm Formation
by Muhammad Shahab, Muhammad Danial, Taimur Khan, Chaoqun Liang, Xiuyuan Duan, Daixi Wang, Hanzi Gao and Guojun Zheng
Biomedicines 2023, 11(3), 961; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11030961 - 21 Mar 2023
Cited by 6 | Viewed by 1688
Abstract
Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium implicated in acute and chronic nosocomial infections and a leading cause of patient mortality. Pseudomonas aeruginosa infections are frequently associated with the development of biofilms, which give the bacteria additional drug resistance and increase their virulence. [...] Read more.
Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium implicated in acute and chronic nosocomial infections and a leading cause of patient mortality. Pseudomonas aeruginosa infections are frequently associated with the development of biofilms, which give the bacteria additional drug resistance and increase their virulence. The goal of this study was to find strong compounds that block the Anthranilate-CoA ligase enzyme made by the pqsA gene. This would stop the P. aeruginosa quorum signaling system. This enzyme plays a crucial role in the pathogenicity of P. aeruginosa by producing autoinducers for cell-to-cell communication that lead to the production of biofilms. Pharmacophore-based virtual screening was carried out utilizing a library of commercially accessible enzyme inhibitors. The most promising hits obtained during virtual screening were put through molecular docking with the help of MOE. The virtual screening yielded 7/160 and 10/249 hits (ZINC and Chembridge). Finally, 2/7 ZINC hits and 2/10 ChemBridge hits were selected as potent lead compounds employing diverse scaffolds due to their high pqsA enzyme binding affinity. The results of the pharmacophore-based virtual screening were subsequently verified using a molecular dynamic simulation-based study (MDS). Using MDS and post-MDS, the stability of the complexes was evaluated. The most promising lead compounds exhibited a high binding affinity towards protein-binding pocket and interacted with the catalytic dyad. At least one of the scaffolds selected will possibly prove useful for future research. However, further scientific confirmation in the form of preclinical and clinical research is required before implementation. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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17 pages, 9910 KiB  
Article
Identification of Natural Lead Compounds against Hemagglutinin-Esterase Surface Glycoprotein in Human Coronaviruses Investigated via MD Simulation, Principal Component Analysis, Cross-Correlation, H-Bond Plot and MMGBSA
by Iqra Ali, Muhammad Asif Rasheed, Simona Cavalu, Kashif Rahim, Sana Ijaz, Galal Yahya, Lucky Poh Wah Goh and Mihaela Simona Popoviciu
Biomedicines 2023, 11(3), 793; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11030793 - 06 Mar 2023
Cited by 7 | Viewed by 2228
Abstract
The pandemic outbreak of human coronavirus is a global health concern that affects people of all ages and genders, but there is currently still no effective, approved and potential drug against human coronavirus, as many other coronavirus vaccines have serious side effects while [...] Read more.
The pandemic outbreak of human coronavirus is a global health concern that affects people of all ages and genders, but there is currently still no effective, approved and potential drug against human coronavirus, as many other coronavirus vaccines have serious side effects while the development of small antiviral inhibitors has gained tremendous attention. For this research, HE was used as a therapeutic target, as the spike protein displays a high binding affinity for both host ACE2 and viral HE glycoprotein. Molecular docking, pharmacophore modelling and virtual screening of 38,000 natural compounds were employed to find out the best natural inhibitor against human coronaviruses with more efficiency and fewer side effects and further evaluated via MD simulation, PCA, DCCR and MMGBSA. The lead compound ‘Calceolarioside B’ was identified on the basis of pharmacophoric features which depict favorable binding (ΔGbind −37.6799 kcal/mol) with the HE(5N11) receptor that describes positive correlation movements in active site residues with better stability, a robust H-bond network, compactness and reliable ADMET properties. The Fraxinus sieboldiana Blume plant containing the Calceolarioside B compound could be used as a potential inhibitor that shows a higher efficacy and potency with fewer side effects. This research work will aid investigators in the testing and identification of chemicals that are effective and useful against human coronavirus. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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11 pages, 1363 KiB  
Article
In Vitro Pharmacokinetic Behavior of Antiviral 3-Amidinophenylalanine Derivatives in Rat, Dog and Monkey Hepatocytes
by Katalin Lányi, Katalin Monostory, Torsten Steinmetzer, Ákos Jerzsele and Erzsébet Pászti-Gere
Biomedicines 2023, 11(3), 682; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11030682 - 23 Feb 2023
Viewed by 1174
Abstract
Type II transmembrane serine proteases represent pharmacological targets for blocking entry and spread of influenza or coronaviruses. In this study, the depletion rates of the 3-amidinophenylalanine (3-APhA)-derived matriptase/TMPRSS2 inhibitors MI-463, MI-472, MI-485 or MI-1900 were determined by LC-MS/MS measurements over a period of [...] Read more.
Type II transmembrane serine proteases represent pharmacological targets for blocking entry and spread of influenza or coronaviruses. In this study, the depletion rates of the 3-amidinophenylalanine (3-APhA)-derived matriptase/TMPRSS2 inhibitors MI-463, MI-472, MI-485 or MI-1900 were determined by LC-MS/MS measurements over a period of 300 min using suspensions of rat, dog and cynomolgus monkey primary hepatocytes. From these in vitro pharmacokinetic (PK) experiments, intrinsic clearance values (Clint) were evaluated, and in vivo pharmacokinetic parameters (hepatic clearance, hepatic extraction ratio and bioavailability) were predicted. It was found that rat hepatocytes were the most active in the metabolism of 3-APhA derivatives (Clint 31.9–37.8 mL/min/kg), whereas dog and monkey cells displayed somewhat lower clearance of these compounds (Clint 6.6–26.7 mL/min/kg). These data support elucidation of important PK properties of anti-TMPRSS2/anti-matriptase 3-APhAs using mammalian hepatocyte models and thus contribute to the optimization of lead compounds. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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12 pages, 2013 KiB  
Article
Reversal of Azole Resistance in Candida albicans by Human Neutrophil Peptide
by Mohammad Imran Khan, Hani Choudhry, Sadaf Jahan and Irfan A. Rather
Biomedicines 2023, 11(2), 513; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11020513 - 10 Feb 2023
Viewed by 1327
Abstract
With the spread of AIDS and the increase in immunocompromised patients, multi-drug-resistant fungal infections have become a serious concern among clinicians, predominantly in the developing world. Therefore, developing novel strategies and new drugs is essential to overcome drug resistance in fungal pathogens. Antimicrobial [...] Read more.
With the spread of AIDS and the increase in immunocompromised patients, multi-drug-resistant fungal infections have become a serious concern among clinicians, predominantly in the developing world. Therefore, developing novel strategies and new drugs is essential to overcome drug resistance in fungal pathogens. Antimicrobial peptides of human origin have been investigated as a potential treatment against Candida infections. In this study, human neutrophil peptide (HNP) was tested for its antifungal activity alone and in combination with fluconazole (FLC) against azole-susceptible and resistant C. albicans isolates, following CLSI guidelines. Susceptibility and combination interactions were also confirmed by MUSE cell viability assay and isobolograms for synergistic combinations, respectively. The effect of HNP on biofilm inhibition was determined spectrophotometrically and microscopically. Drug susceptibility testing showed minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) ranging from 7.813 to 62.5 µg/mL and 15.625 to 250 µg/mL against all the tested C. albicans strains. The combination activity of FLC with HNP exhibited synergistic and additive interactions in 43% of each and indifferent interaction in 14%, and none of the combinations showed antagonistic interaction. Furthermore, HNB inhibited biofilm formation in all the tested C. albicans isolates. At the respective MICs, HNP exhibited inhibitory effects on the activity of the drug efflux pumps and their genes. These results warrant the application of HNP as a mono- or combination therapy with FLC to treat azole-resistant C. albicans. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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21 pages, 5419 KiB  
Article
Multi-Omic Profiling, Structural Characterization, and Potent Inhibitor Screening of Evasion-Related Proteins of a Parasitic Nematode, Haemonchus contortus, Surviving Vaccine Treatment
by Nikola Palevich, Paul H. Maclean, Vincenzo Carbone, Ruy Jauregui and Saleh Umair
Biomedicines 2023, 11(2), 411; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11020411 - 30 Jan 2023
Cited by 1 | Viewed by 2447
Abstract
The emergence of drug-resistant parasitic nematodes in both humans and livestock calls for development of alternative and cost-effective control strategies. Barbervax® is the only registered vaccine for the economically important ruminant strongylid Haemonchus contortus. In this study, we compared the microbiome, [...] Read more.
The emergence of drug-resistant parasitic nematodes in both humans and livestock calls for development of alternative and cost-effective control strategies. Barbervax® is the only registered vaccine for the economically important ruminant strongylid Haemonchus contortus. In this study, we compared the microbiome, genome-wide diversity, and transcriptome of H. contortus adult male populations that survived vaccination with an experimental vaccine after inoculation in sheep. Our genome-wide SNP analysis revealed 16 putative candidate vaccine evasion genes. However, we did not identify any evidence for changes in microbial community profiling based on the 16S rRNA gene sequencing results of the vaccine-surviving parasite populations. A total of fifty-eight genes were identified as significantly differentially expressed, with six genes being long non-coding (lnc) RNAs and none being putative candidate SNP-associated genes. The genes that highly upregulated in surviving parasites from vaccinated animals were associated with GO terms belonging to predominantly molecular functions and a few biological processes that may have facilitated evasion or potentially lessened the effect of the vaccine. These included five targets: astacin (ASTL), carbonate dehydratase (CA2), phospholipase A2 (PLA2), glutamine synthetase (GLUL), and fatty acid-binding protein (FABP3). Our tertiary structure predictions and modelling analyses were used to perform in silico searches of all published and commercially available inhibitor molecules or substrate analogs with potential broad-spectrum efficacy against nematodes of human and veterinary importance. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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14 pages, 12381 KiB  
Article
A Subset Screen of the Compounds Australia Scaffold Library Identifies 7-Acylaminodibenzoxazepinones as Potent and Selective Hits for Anti-Giardia Drug Discovery
by Christopher J. S. Hart, Andrew G. Riches, Snigdha Tiash, Erin Clapper, Soumya Ramu, Johannes Zuegg, John H. Ryan and Tina S. Skinner-Adams
Biomedicines 2022, 10(12), 3182; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123182 - 08 Dec 2022
Cited by 2 | Viewed by 1230
Abstract
On an annual basis the flagellate protozoan, Giardia duodenalis, is responsible for an estimated one billion human infections of which approximately two hundred million cause disease. However, the treatment of Giardia infections is reliant on a small group of chemotherapeutic classes that [...] Read more.
On an annual basis the flagellate protozoan, Giardia duodenalis, is responsible for an estimated one billion human infections of which approximately two hundred million cause disease. However, the treatment of Giardia infections is reliant on a small group of chemotherapeutic classes that have a broad spectrum of antimicrobial activity and increasing treatment failure rates. To improve this situation, we need new drugs. In this study we screened the Compounds Australia Scaffolds Library for compounds with potent and selective activity against these parasites. Unlike previous drug discovery efforts that have focused on drug repurposing, this library is comprised of commercially available synthetic compounds arranged into lead-like scaffolds to facilitate structure activity relationship assessments and de novo drug discovery. A screen of 2451 compounds in this library identified 40 hits (>50% inhibitory activity at 10 µM, over 48 h). Secondary testing identified three compounds with IC50 values <1 μM and >50-fold selectivity for parasites over mammalian cells and a hit series, CL9406, comprising compounds with potent (lowest IC50 180 nM) and selective activity for Giardia parasites. The most promising compound in this series, SN00797640, displayed selective activity against assemblage A, B, and metronidazole resistant parasites which was parasiticidal (minimum lethal concentration 625 nM) and synergistic with albendazole. SN00797640 was well-tolerated when administered to mice at doses of 50 mg/kg daily for three days paving the way for pre-clinical in vivo activity assessment. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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15 pages, 1504 KiB  
Article
Photoreactive Coating Material as an Effective and Durable Antimicrobial Composite in Reducing Bacterial Load on Surfaces in Livestock
by Ádám Kerek, Mátyás Sasvári, Ákos Jerzsele, Zoltán Somogyi, László Janovák, Zsolt Abonyi-Tóth and Imre Dékány
Biomedicines 2022, 10(9), 2312; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10092312 - 17 Sep 2022
Cited by 1 | Viewed by 1392
Abstract
Titanium dioxide (TiO2) is a well-known photocatalytic compound that can be used to effectively reduce the presence of pathogens in human and animal hospitals via ROS release. The aim of this study was to investigate the efficacy of a polymer-based composite [...] Read more.
Titanium dioxide (TiO2) is a well-known photocatalytic compound that can be used to effectively reduce the presence of pathogens in human and animal hospitals via ROS release. The aim of this study was to investigate the efficacy of a polymer-based composite layer containing TiO2 and zinc oxide (ZnO) against Escherichia coli (E. coli) of animal origin. We showed that the photocatalyst coating caused a significant (p < 0.001) reduction in pathogen numbers compared to the control with an average reduction of 94% over 30 min. We used six light sources of different wattages (4 W, 7 W, 9 W, 12 W, 18 W, 36 W) at six distances (35 cm, 100 cm, 150 cm, 200 cm, 250 cm, 300 cm). Samples (n = 2160) were taken in the 36 settings and showed no significant difference in efficacy between light intensity and distance. We also investigated the influence of organic contaminant that resulted in lower activity as well as the effect of a water jet and a high-pressure device on the antibacterial activity. We found that the latter completely removed the coating from the surface, which significantly (p < 0.0001) reduced its antibacterial potential. As a conclusion, light intensity and distance does not reduce the efficacy of the polymer, but the presence of organic contaminants does. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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10 pages, 1108 KiB  
Article
Klebsiella pneumoniae Susceptibility to Carbapenem/Relebactam Combinations: Influence of Inoculum Density and Carbapenem-to-Inhibitor Concentration Ratio
by Maria V. Golikova, Kamilla N. Alieva, Alla V. Filimonova, Vladimir A. Ageevets, Ofeliia S. Sulian, Alisa A. Avdeeva, Sergey V. Sidorenko and Stephen H. Zinner
Biomedicines 2022, 10(6), 1454; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10061454 - 20 Jun 2022
Cited by 2 | Viewed by 1848
Abstract
The inoculum effect (IE) is a well-known phenomenon with beta-lactams. At the same time, the IE has not been extensively studied with carbapenem/carbapenemase inhibitor combinations. The antibiotic-to-inhibitor concentration ratio used in susceptibility testing can influence the in vitro activity of the combination. To [...] Read more.
The inoculum effect (IE) is a well-known phenomenon with beta-lactams. At the same time, the IE has not been extensively studied with carbapenem/carbapenemase inhibitor combinations. The antibiotic-to-inhibitor concentration ratio used in susceptibility testing can influence the in vitro activity of the combination. To explore the role of these factors, imipenem/relebactam and doripenem/relebactam MICs were estimated against six Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae strains at standard inocula (SI) and high inocula (HI) by two methods: with a fixed relebactam concentration and with a fixed, pharmacokinetic-based carbapenem-to-relebactam concentration ratio. The combination MICs at HI, compared to SI, increased with most of the tested strains. However, the IE occurred with only two K. pneumoniae strains regardless of the MIC testing method. The relationship between the MICs at SI and the respective inoculum-induced MIC changes was observed when the MICs were estimated at pharmacokinetic-based carbapenem-to-relebactam concentration ratios. Thus, (1) IE was observed with both carbapenem/relebactam combinations regardless of the MIC testing method; however, IE was not observed frequently among tested K. pneumoniae strains. (2) At HI, carbapenem/relebactam combination MICs increased to levels associated with carbapenem resistance. (3) Combination MICs determined at pharmacokinetic-based carbapenem-to-inhibitor concentration ratios predict susceptibility elevations at HI in KPC-producing K. pneumoniae. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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32 pages, 7747 KiB  
Article
Anti-Quorum Sensing Activities of Gliptins against Pseudomonas aeruginosa and Staphylococcus aureus
by Maan T. Khayat, Hisham A. Abbas, Tarek S. Ibrahim, Ahdab N. Khayyat, Majed Alharbi, Khaled M. Darwish, Sameh S. Elhady, El-Sayed Khafagy, Martin K. Safo and Wael A. H. Hegazy
Biomedicines 2022, 10(5), 1169; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051169 - 18 May 2022
Cited by 22 | Viewed by 2882
Abstract
The development of bacterial resistance to traditional antibiotics constitutes an emerging public health issue. Promising approaches have been innovated to conquer bacterial resistance, and targeting bacterial virulence is one of these approaches. Bacterial virulence mitigation offers several merits, as antivirulence agents do not [...] Read more.
The development of bacterial resistance to traditional antibiotics constitutes an emerging public health issue. Promising approaches have been innovated to conquer bacterial resistance, and targeting bacterial virulence is one of these approaches. Bacterial virulence mitigation offers several merits, as antivirulence agents do not affect the growth of bacteria and hence do not induce bacteria to develop resistance. In this direction, numerous drugs have been repurposed as antivirulence agents prior to their clinical use alone or in combination with traditional antibiotics. Quorum sensing (QS) plays a key role in controlling bacterial virulence. In the current study, dipeptidase inhibitor-4 (DPI-4) antidiabetic gliptins were screened for their antivirulence and anti-quorum sensing (anti-QS) activities against Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus. Upon assessing their antibiofilm activities, the ten tested gliptins significantly diminished biofilm formation. In particular, sitagliptin exhibited the most efficient antibiofilm activity, so it was chosen as a representative of all gliptins to further investigate its antivirulence activity. Sitagliptin significantly protected mice from P. aeruginosa and S. aureus pathogenesis. Furthermore, sitagliptin downregulated QS-encoding genes in P. aeruginosa and S. aureus. To test the anti-QS activities of gliptins, a detailed molecular docking study was conducted to evaluate the gliptins’ binding affinities to P. aeruginosa and S. aureus QS receptors, which helped explain the anti-QS activities of gliptins, particularly sitagliptin and omarigliptin. In conclusion, this study evaluates the possible antivirulence and anti-QS activities of gliptins that could be promising novel candidates for the treatment of aggressive Gram-negative or -positive bacterial infections either alone or as adjuvants to other antibiotics. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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Review

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14 pages, 2070 KiB  
Review
Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects
by Mohd. Imran, Mohammed Kanan Alshammari, Mandeep Kumar Arora, Amit Kumar Dubey, Sabya Sachi Das, Mehnaz Kamal, Abdulaziz Saad Abdulrahman Alqahtani, Mohammed Ahmed Yahya Sahloly, Ahmed Hammad Alshammari, Hessah Mohammed Alhomam, Aeshah Mousa Mahzari, Abida, Ali A. Rabaan and Tafadzwa Dzinamarira
Biomedicines 2023, 11(2), 278; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11020278 - 19 Jan 2023
Cited by 8 | Viewed by 2749
Abstract
The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and [...] Read more.
The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022. Full article
(This article belongs to the Special Issue Drug Discovery for Infectious Diseases)
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