scholarly journals Construction of antifungal dual-target (SE, CYP51) pharmacophore models and the discovery of novel antifungal inhibitors

RSC Advances ◽  
2019 ◽  
Vol 9 (45) ◽  
pp. 26302-26314 ◽  
Author(s):  
Yue Dong ◽  
Min Liu ◽  
Jian Wang ◽  
Zhuang Ding ◽  
Bin Sun
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
External Environment ◽  
Pharmacophore Models ◽  
Dual Target

Fungal infections and drug-resistance are rapidly increasing with the deterioration of the external environment.

Anti-Candida activity of existing antibiotics and their derivatives when used alone or in combination with antifungals

2019 ◽  
Vol 14 (10) ◽  
pp. 899-915 ◽  
Author(s):  
Yaxin Liu ◽  
Weixin Wang ◽  
Haiying Yan ◽  
Decai Wang ◽  
Min Zhang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Therapeutic Strategies ◽  
Candida Infection ◽  
Immunocompromised Patients ◽  
Derivatives Of

Fungal infections are a growing challenge in immunocompromised patients, especially candidiasis. The prolonged use of traditional antifungals to treat Candida infection has caused the emergence of drug resistance, especially fluconazole. Therefore, new therapeutic strategies for Candida infection are warranted. Recently, attention has been paid to the anti- Candida activity of antibiotics and their derivatives. Studies revealed that a series of antibiotics/derivatives displayed potential anti- Candida activity and some of them could significantly increase the susceptibility of antifungals. Interestingly, the derivatives of aminoglycosides were even more active than fluconazole/itraconazole/posaconazole. This article reviews the anti- Candida activities and mechanisms of antibiotics/derivatives used alone or in combination with antifungals. This review will helpfully provide novel insights for overcoming Candida resistance and discovering new antifungals.

Prediction of the binding mode and resistance profile for a dual-target pyrrolyl diketo acid scaffold against HIV-1 integrase and reverse-transcriptase-associated ribonuclease H

2018 ◽  
Vol 20 (37) ◽  
pp. 23873-23884 ◽  
Author(s):  
Fengyuan Yang ◽  
Guoxun Zheng ◽  
Tingting Fu ◽  
Xiaofeng Li ◽  
Gao Tu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Binding Mode ◽  
Hiv Treatment ◽  
Rnase H ◽  
Ribonuclease H ◽  
Resistance Profile ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Dual Target

The recently developed pyrrolyl diketo acid scaffold targeting both HIV-1 IN and RNase H is beneficial to counteract the failure of anti-HIV treatment due to drug resistance.

scholarly journals Dehydrozingerone Exhibits Synergistic Antifungal Activities in Combination with Dodecanol against Budding Yeast via the Restriction of Multidrug Resistance

2018 ◽  
Vol 5 (02) ◽  
pp. e61-e67
Author(s):  
Chika Yamawaki ◽  
Yoshihiro Yamaguchi ◽  
Akira Ogita ◽  
Toshio Tanaka ◽  
Ken-ichi Fujita
Keyword(s):  
Drug Resistance ◽  
Antifungal Activity ◽  
Efflux Pump ◽  
Fungal Infections ◽  
Zingiber Officinale ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Yeast Saccharomyces Cerevisiae ◽  
Multidrug Transporters ◽  
Multidrug Efflux Pumps

AbstractDrug resistance in fungal infections has been a more frequent occurrence with the increasing number of immunocompromised patients. In efforts to overcome the problem of fungal drug resistance, we focused on the phenolic compound dehydrozingerone, which is isolated from Zingiber officinale. The effectiveness of this compound on the model yeast Saccharomyces cerevisiae has not been reported. In our study, dehydrozingerone showed a weak antifungal activity against the yeast, but demonstrated a synergistic effect in combination with dodecanol, which typically only restricts cell growth transiently. Efflux of rhodamine 6G through the multidrug efflux pumps was significantly restricted by dehydrozingerone. The transcription level of PDR5, encoding a primary multidrug efflux pump in S. cerevisiae, was enhanced with dodecanol treatment, whereas the level was reduced by dehydrozingerone. These results suggest that dehydrozingerone may be effective for potentiating antifungal activity of other drugs that are expelled from fungi by multidrug transporters like Pdr5p.

scholarly journals COVID-19: CRISPR/Cas-like System of nsp3 Promotes the Mutant Recombination and Drug Resistance

2021 ◽  
Author(s):  
liu wenzhong ◽  
Li hualan
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Fungal Spores ◽  
Virus Genome ◽  
Virus Protein ◽  
Coding Region ◽  
Conserved Domains ◽  
Negative Strand ◽  
Bacteria And Fungi ◽  
Novel Coronavirus

<p>Patients with novel coronavirus pneumonia usually suffer from bacterial and fungal infections, and the drug resistance problem caused by the pandemic is becoming more and more serious. Simultaneously, the SARS-COV-2 virus has a rapid mutation phenomenon, and somegene coding regions by mutation and recombination may be related to the drug resistance of the virus. Therefore, studying the relationship between the co-infection of bacteria and fungi and the evolution of SARS-COV-2 has important guiding significance for preventing a pandemic. We found that the SARS-COV-2 virus's nsp3 protein had a CRISPR/Cas 9 (II-B)-like function by searching for conserved domains. The system could target and edit the negative-strand RNA of SARS-COV-2. We speculated that the crRNA (CRISPR RNA) produced by the CRISPR/Cas system of Pseudomonas aeruginosa carried the genetic information of the conserved domains of bacteriophages and Pseudomonas, including drug resistance. After the phage lysed the Pseudomonas, the crRNA was released and attached to the fungal spores, and then invaded the patient's cells along with the spores or hyphae. nsp3 synthesized and assembled 4Fe-4S, iron-containing molecules bound to the cas4 domain, in the mitochondria of phagocytes. The iron came from hemoglobin attacked by the SARS-COV-2 virus protein. The nsp3 protein bound the crRNA in the phagocytic cytoplasm. It targeted the negative-strand RNA of SARS-COV-2, inserting conserved domain gene fragments into the negative-strand RNA through editing and splicing. Since the Cas protein had no codon checking function, the cutting and splicing would destroy the protein-coding information in the original RNA coding region, causing mutation and recombination of the SARS-COV-2 virus genome. If crRNA carried the drug resistance gene fragments of bacteria or phage, SARS-COV-2 would have similar drug resistance. Because of the growing problem of drug resistance in COVID-19 patients, we should pay attention to preventing fungi and bacteria co-infection. Avoid the CRISPR/Cas-like system of the novel coronavirus to cause rapid mutation and recombination and increased the drug resistance problem of SARS-COV-2.</p>

scholarly journals COVID-19: CRISPR/Cas-like System of nsp3 Promotes the Mutant Recombination and Drug Resistance

2021 ◽  
Author(s):  
liu wenzhong ◽  
Li hualan
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Fungal Spores ◽  
Virus Genome ◽  
Virus Protein ◽  
Coding Region ◽  
Conserved Domains ◽  
Negative Strand ◽  
Bacteria And Fungi ◽  
Novel Coronavirus

<p>Patients with novel coronavirus pneumonia usually suffer from bacterial and fungal infections, and the drug resistance problem caused by the pandemic is becoming more and more serious. Simultaneously, the SARS-COV-2 virus has a rapid mutation phenomenon, and somegene coding regions by mutation and recombination may be related to the drug resistance of the virus. Therefore, studying the relationship between the co-infection of bacteria and fungi and the evolution of SARS-COV-2 has important guiding significance for preventing a pandemic. We found that the SARS-COV-2 virus's nsp3 protein had a CRISPR/Cas 9 (II-B)-like function by searching for conserved domains. The system could target and edit the negative-strand RNA of SARS-COV-2. We speculated that the crRNA (CRISPR RNA) produced by the CRISPR/Cas system of Pseudomonas aeruginosa carried the genetic information of the conserved domains of bacteriophages and Pseudomonas, including drug resistance. After the phage lysed the Pseudomonas, the crRNA was released and attached to the fungal spores, and then invaded the patient's cells along with the spores or hyphae. nsp3 synthesized and assembled 4Fe-4S, iron-containing molecules bound to the cas4 domain, in the mitochondria of phagocytes. The iron came from hemoglobin attacked by the SARS-COV-2 virus protein. The nsp3 protein bound the crRNA in the phagocytic cytoplasm. It targeted the negative-strand RNA of SARS-COV-2, inserting conserved domain gene fragments into the negative-strand RNA through editing and splicing. Since the Cas protein had no codon checking function, the cutting and splicing would destroy the protein-coding information in the original RNA coding region, causing mutation and recombination of the SARS-COV-2 virus genome. If crRNA carried the drug resistance gene fragments of bacteria or phage, SARS-COV-2 would have similar drug resistance. Because of the growing problem of drug resistance in COVID-19 patients, we should pay attention to preventing fungi and bacteria co-infection. Avoid the CRISPR/Cas-like system of the novel coronavirus to cause rapid mutation and recombination and increased the drug resistance problem of SARS-COV-2.</p>

Pathogenesis of Fungal Infections and Drug-Resistance Phenomenon

2020 ◽  
pp. 323-347
Author(s):  
Sudhakar Pola ◽  
Akella Vijayaramya ◽  
Pavani Sanapala ◽  
V. A. Iswarya Deepthi
Keyword(s):  
Drug Resistance ◽  
Fungal Infections

Targeting stress response pathways with alternative strategies as a novel antifungal approach

2021 ◽  
Vol 21 ◽  
Author(s):  
Sonam Ruhil ◽  
Vikash Kumar ◽  
Meenakshi Balhara ◽  
Monika Malik ◽  
Anil K. Chhillar
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Essential Gene ◽  
Fungal Growth ◽  
High Morbidity ◽  
Invasive Infection ◽  
Alternative Strategies ◽  
Antifungal Drug Resistance ◽  
Novel Approach ◽  
Stress Pathway

: Fungi are recognized as key pathogens in immunocompromised patients. The invasive infection always remains a problem for clinician due to high morbidity and mortality. The treatments of fungal infections are hampered by conventional drugs which are associated with resistance. Drug resistance has become an important problem in a variety of infectious diseases. The rise in the incidence of fungal infections and drug resistance has intensified the need for alternate therapies that affect a new target. This new target must be a growth essential gene product like stress pathway. It has been found that stress pathways can be a potential target in opportunistic fungal infection which played important role in virulence of pathogens. It was helpful in protection from host defense, normal fungal growth and antifungal drug resistance. The disruption of pathway using alternative strategies (chemosensitization and photo-dynamics therapy) can be a novel approach in fighting fungal infections and for drug design.

scholarly journals Prevalence and Therapeutic Challenges of Fungal Drug Resistance: Role for Plants in Drug Discovery

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 150 ◽  
Author(s):  
Lewis Marquez ◽  
Cassandra L. Quave
Keyword(s):  
United States ◽  
Drug Resistance ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Modern Medicine ◽  
Candida Auris ◽  
Medical Ethnobotany ◽  
Global Issue

Antimicrobial resistance is a global issue that threatens the effective practice of modern medicine and global health. The emergence of multidrug-resistant (MDR) fungal strains of Candida auris and azole-resistant Aspergillus fumigatus were highlighted in the Centers for Disease Control and Prevention’s (CDC) 2019 report, Antibiotic Resistance Threats in the United States. Conventional antifungals used to treat fungal infections are no longer as effective, leading to increased mortality. Compounding this issue, there are very few new antifungals currently in development. Plants from traditional medicine represent one possible research path to addressing the issue of MDR fungal pathogens. In this commentary piece, we discuss how medical ethnobotany—the study of how people use plants in medicine—can be used as a guide to identify plant species for the discovery and development of novel antifungal therapies.

Progress and prospects for targeting Hsp90 to treat fungal infections

Parasitology ◽  
2014 ◽  
Vol 141 (9) ◽  
pp. 1127-1137 ◽  
Author(s):  
AMANDA VERI ◽  
LEAH E. COWEN
Keyword(s):  
Drug Resistance ◽  
Anticancer Agents ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Effective Combination ◽  
New Strategy ◽  
Life Threatening ◽  
Hsp90 Chaperone ◽  
Hsp90 Function

SummaryFungal pathogens pose a major threat to human health worldwide. They infect billions of people each year, leading to at least 1·5 million deaths. Treatment of fungal infections is difficult due to the limited number of clinically useful antifungal drugs, and the emergence of drug resistance. A promising new strategy to enhance the efficacy of antifungal drugs and block the evolution of drug resistance is to target the molecular chaperone Hsp90. Pharmacological inhibitors of Hsp90 function that are in development as anticancer agents have potential to be repurposed as agents for combination antifungal therapy for some applications, such as biofilm infections. For systemic infections, however, effective combination therapy regimens may require Hsp90 inhibitors that can selectively target Hsp90 in the pathogen, or alternate strategies to compromise function of the Hsp90 chaperone machine. Selectively impairing Hsp90 function in the pathogen could in principle be achieved by targeting Hsp90 co-chaperones or regulators of Hsp90 function that are more divergent between pathogen and host than Hsp90. Antifungal combination therapies could also exploit downstream effectors of Hsp90 that are critical for fungal drug resistance and virulence. Here, we discuss the progress and prospects for establishing Hsp90 as an important therapeutic target for life-threatening fungal infections.

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