scholarly journals Drug Repurposing for Tuberculosis

2021 ◽  
Author(s):  
Nicole C. Cardoso ◽  
Carel B. Oosthuizen ◽  
Nashied Peton ◽  
Vinayak Singh
Keyword(s):  
Drug Repurposing ◽  
Drug Efficacy ◽  
Health Concern ◽  
Current Status ◽  
Drug Resistant ◽  
Drug Candidates ◽  
Repurposed Drugs ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Discovery Pipeline

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major global health concern given the increase in multiple forms of drug-resistant TB. This underscores the importance of a continuous pipeline of new anti-TB agents. From recent studies, it is evident that the increase in drug efficacy is being achieved through re-engineering old TB-drug families and repurposing known drugs. This approach has led to producing a newer class of compounds which not only saves time and investment in developing newer drugs but is also effective in identifying drug candidates with novel mechanisms to treat multi-drug resistant strains. The repurposed drugs moxifloxacin, linezolid, and clofazimine are used to treat extensively drug-resistant TB when first- and/or second-line drugs fail. The chapter covers a detailed background on the current status of the repurposed drugs in the TB drug-discovery pipeline and discusses a potential way forward.

Mycobacterium tuberculosis topoisomerases and EthR as the targets for new anti-TB drugs development

2019 ◽  
Vol 11 (16) ◽  
pp. 2193-2203
Author(s):  
Rafal Sawicki ◽  
Grazyna Ginalska
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Short Review ◽  
Drug Resistant ◽  
Dna Topoisomerases ◽  
Antituberculosis Drugs ◽  
Drug Candidates ◽  
Computational Sciences ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
New Strategies

The significant increase in the detection of drug-resistant strains of Mycobacterium tuberculosis caused an urgent need for the discovery new antituberculosis drugs. Development of bioinformatics and computational sciences enabled the progress of new strategies leading to design, discovery and identification of a series of interesting drug candidates. In this short review, we would like to present recently discovered compounds targeting important mycobacterial proteins: DNA topoisomerases and the transcriptional repressor of EthA monooxygenase – EthR.

scholarly journals Recombinant ESAT-6-Like Proteins Provoke Protective Immune Responses against Invasive Staphylococcus aureus Disease in a Murine Model

2014 ◽  
Vol 83 (1) ◽  
pp. 339-345 ◽  
Author(s):  
Bao Zhong Zhang ◽  
Yan Hong Hua ◽  
Bin Yu ◽  
Candy Choi Yi Lau ◽  
Jian Piao Cai ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Survival Rates ◽  
Passive Immunization ◽  
Health Concern ◽  
Drug Resistant ◽  
Public Health Concern ◽  
Content Type ◽  
Resistant Strains ◽  
Drug Resistant Strains

Staphylococcus aureusis a common pathogen found in the community and in hospitals. Most notably, methicillin-resistantS. aureusis resistant to many antibiotics, which is a growing public health concern. The emergence of drug-resistant strains has prompted the search for alternative treatments, such as immunotherapeutic approaches. To date, most clinical trials of vaccines or of passive immunization againstS. aureushave ended in failure. In this study, we investigated two ESAT-6-like proteins secreted byS. aureus,S. aureusEsxA (SaEsxA) and SaEsxB, as possible targets for a vaccine. Mice vaccinated with these purified proteins elicited high titers of anti-SaEsxA and anti-SaEsxB antibodies, but these antibodies could not preventS. aureusinfection. On the other hand, recombinant SaEsxA (rSaEsxA) and rSaEsxB could induce Th1- and Th17-biased immune responses in mice. Mice immunized with rSaEsxA and rSaEsxB had significantly improved survival rates when challenged withS. aureuscompared with the controls. These findings indicate that SaEsxA and SaEsxB are two promising Th1 and Th17 candidate antigens which could be developed into multivalent and serotype-independent vaccines againstS. aureusinfection.

scholarly journals Structure-based drug repurposing to inhibit the DNA gyrase of Mycobacterium tuberculosis

2020 ◽  
Vol 477 (21) ◽  
pp. 4167-4190
Author(s):  
Balasubramani GL ◽  
Rinky Rajput ◽  
Manish Gupta ◽  
Pradeep Dahiya ◽  
Jitendra K. Thakur ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Repurposing ◽  
Dna Gyrase ◽  
Dna Supercoiling ◽  
New Drugs ◽  
Resonance Spectroscopy ◽  
Drug Resistant ◽  
Ic50 Values ◽  
Resistant Strains ◽  
Drug Resistant Strains

Drug repurposing is an alternative avenue for identifying new drugs to treat tuberculosis (TB). Despite the broad-range of anti-tubercular drugs, the emergence of multi-drug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis (Mtb) H37Rv, as well as the significant death toll globally, necessitates the development of new and effective drugs to treat TB. In this study, we have employed a drug repurposing approach to address this drug resistance problem by screening the drugbank database to identify novel inhibitors of the Mtb target enzyme, DNA gyrase. The compounds were screened against the ATPase domain of the gyrase B subunit (MtbGyrB47), and the docking results showed that echinacoside, doxorubicin, epirubicin, and idarubicin possess high binding affinities against MtbGyrB47. Comprehensive assessment using fluorescence spectroscopy, surface plasmon resonance spectroscopy (SPR), and circular dichroism (CD) titration studies revealed echinacoside as a potent binder of MtbGyrB47. Furthermore, ATPase, and DNA supercoiling assays exhibited an IC50 values of 2.1–4.7 µM for echinacoside, doxorubicin, epirubicin, and idarubicin. Among these compounds, the least MIC90 of 6.3 and 12 μM were observed for epirubicin and echinacoside, respectively, against Mtb. Our findings indicate that echinacoside and epirubicin targets mycobacterial DNA gyrase, inhibit its catalytic cycle, and retard mycobacterium growth. Further, these compounds exhibit potential scaffolds for optimizing novel anti-mycobacterial agents that can act on drug-resistant strains.

scholarly journals Gonorrhoea: past, present and future

2020 ◽  
Vol 41 (4) ◽  
pp. 205
Author(s):  
Evgeny A Semchenko ◽  
Xiaofan Chen ◽  
Caroline Thng ◽  
Maree O'Sullivan ◽  
Kate L Seib
Keyword(s):  
Bacterial Pathogen ◽  
Health Concern ◽  
Drug Resistant ◽  
Transmitted Infection ◽  
Gram Negative ◽  
Sexually Transmitted ◽  
High Prevalence ◽  
Public Health Threat ◽  
Resistant Strains ◽  
Drug Resistant Strains

The sexually transmitted infection (STI) gonorrhoea is an ancient human disease caused by the Gram-negative bacterial pathogen Neisseria gonorrhoeae. Despite decades of research focused on preventing, diagnosing, and treating gonorrhoea, it remains a major global health concern due to its high prevalence, high rates of asymptomatic cases, the severe sequelae that can result from untreated infections, and the increasing difficulty in treating infections caused by multi-drug resistant strains of N. gonorrhoeae. It is estimated that there are more than 87 million cases of gonorrhoea worldwide each year, and the WHO, CDC and Australian National Antimicrobial Resistance (AMR) Strategy have prioritised N. gonorrhoeae as an urgent public health threat for which new therapeutics and a vaccine are needed.

scholarly journals Attaching Zanamivir to a Polymer Markedly Enhances Its Activity Against Drug-resistant Strains of Influenza a Virus

2011 ◽  
Vol 100 (3) ◽  
pp. 831-835 ◽  
Author(s):  
Alisha K. Weight ◽  
Jayanta Haldar ◽  
Luis Álvarez de Cienfuegos ◽  
Larisa V. Gubareva ◽  
Terrence M. Tumpey ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

DRUG RESISTANT STRAINS OF PLASMODIUM FALCIPARUM IN PAPUA NEW GUINEA

The Lancet ◽  
1981 ◽  
Vol 317 (8216) ◽  
pp. 386
Author(s):  
Brian Darlow ◽  
Helena Vrbova ◽  
John Stace ◽  
Peter Heywood ◽  
Michael Alpers
Keyword(s):  
Plasmodium Falciparum ◽  
Papua New Guinea ◽  
New Guinea ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

Tigecycline for Treatment of Nosocomial-Acquired Pneumonia Possibly Caused by Multi-Drug Resistant Strains ofStenotrophomonas maltophilia

2008 ◽  
Vol 20 (6) ◽  
pp. 761-763 ◽  
Author(s):  
D. Blanquer ◽  
J. De Otero ◽  
E. Padilla ◽  
F. Gòmez ◽  
A. Mayol ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses against Mycobacterium bovis BCG Strain in Individuals with Type 2 Diabetes

2021 ◽  
Vol 12 (1) ◽  
pp. 16-26
Author(s):  
Kimberly To ◽  
Ruoqiong Cao ◽  
Aram Yegiazaryan ◽  
James Owens ◽  
Kayvan Sasaninia ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Immune Cells ◽  
Mycobacterial Infection ◽  
Drug Resistant ◽  
Tnf Α ◽  
Resistant Strains ◽  
Ifn Γ ◽  
Drug Resistant Strains

Abstract Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, M. tb still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of M. tb have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within in vitro granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of in vivo glutathione (GSH) supplementation in individuals with T2DM along with in vitro treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects’ blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct in vitro studies with everolimus. We found that in vitro treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular M. bovis BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with in vitro everolimus treatment produced a greater effect in inhibiting the growth of intracellular Mycobacterium bovis BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with in vitro everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, in vitro everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.

Sign in / Sign up

Export Citation Format

Share Document