Drug repurposing screens and synergistic drug‐combinations for infectious diseases

Abstract

Infectious diseases account for nearly one fifth of the worldwide death toll every year. The continuous increase of drug‐resistant pathogens is a big challenge for treatment of infectious diseases. In addition, outbreaks of infections and new pathogens are potential threats to public health. Lack of effective treatments for drug‐resistant bacteria and recent outbreaks of Ebola and Zika viral infections have become a global public health concern. The number of newly approved antibiotics has decreased significantly in the last two decades compared with previous decades. In parallel with this, is an increase in the number of drug‐resistant bacteria. For these threats and challenges to be countered, new strategies and technology platforms are critically needed. Drug repurposing has emerged as an alternative approach for rapid identification of effective therapeutics to treat the infectious diseases. For treatment of severe infections, synergistic drug combinations using approved drugs identified from drug repurposing screens is a useful option which may overcome the problem of weak activity of individual drugs. Collaborative efforts including government, academic researchers and private drug industry can facilitate the translational research to produce more effective new therapeutic agents such as narrow spectrum antibiotics against drug‐resistant bacteria for these global challenges.Linked ArticlesThis article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc

An automated high-throughput system for phenotypic screening of chemical libraries onC. elegansand parasitic nematodes

“…Repurposing of existing drugs for new indications is an established 504 approach in drug discovery (Zheng et al, 2017) and is particularly valuable for neglected tropical 505 . CC-BY 4.0 International license peer-reviewed) is the author/funder.…”

Drug Repurposing for Viral Infectious Diseases: How Far Are We?

“…Promising anti-EBOV activity was determined for selective estrogen receptor modulators (cloremiphene and toremiphene [36,37]), chloroquine and related antimalarial drugs [38], sertraline and bepridil [39], teicoplanin [40], cationic amphiphilic drugs such as amiodarone [41], and the broad-spectrum RNA polymerase inhibitor BCX-4430 [42]. Finally, the frontier of DR to directly test a combination of drugs that have shown antiviral activity (although at concentrations not clinically reachable in humans with the approved regimen) gave successful results [43]. Indeed, a targeted drug combination approach resulted in the identification of two sets of three-drug cocktails (i.e., toremifene-mefloquine-posaconazole and toremifeneclarithromycin-posaconazole, all previously identified by DR) that act synergistically in an EBOV entry-inhibition assay and at concentrations achievable in humans [44].…”

Improving inverse docking target identification with Z‐score selection

“…Small molecule protein target identification is important in a drug discovery process and for understanding molecular function. Being able to identify protein targets of small molecules has important implications for the detection of potential drug side‐effects (Chen & Ung, ; Chen et al., ; Ivanov, Lagunin, Rudik, Filimonov, & Poroikov, ; Mizutani, Pauwels, Stoven, Goto, & Yamanishi, ) and in the repurposing of FDA‐approved drugs (Hernandez et al., ; Zheng, Sun, & Simeonov, ). Additionally, protein target identification can be important to follow up on experimental cell‐based screens or to confirm the binding target of a compound identified by either structure‐based drug discovery or high‐throughput screening in cases where the experimental assay contained multiple proteins.…”