Emerging paradigms in anti-infective drug design

Abstract

The need for new drugs to treat microbial infections is pressing. The great progress made in the middle part of the twentieth Century was followed by a period of relative inactivity as the medical needs relating to infectious disease in the wealthier nations receded. Growing realisation that anti-infectives are needed in many parts of the world, to treat neglected diseases as well as to combat the burgeoning risk of resistance to existing drugs, has galvanised a new wave of research into anti-microbial drugs. The transfer of knowledge from the Pharmaceutical industry relating to the importance of understanding how to target drugs successfully within the body, and improved understanding of how pathogens interact with their hosts, is driving a series of new paradigms in anti-infective drug design. Here we provide an overview of those processes as an introduction to a series of articles from experts in this area that emerged from a meeting entitled “Emerging Paradigms in Anti-Infective Drug Design” held in London on the 17th and 18th September 2012. The symposium was organised jointly by British Society for Parasitology (BSP) and the Biological & Medicinal Chemistry sector of the Royal Society of Chemistry (RSC) and held at the London School of Hygiene & Tropical Medicine. The symposium set out to cover all aspects of the identification of new therapeutic modalities for the treatment of neglected and tropical diseases. We aimed to bring together leading scientists from all the disciplines working in this field and cover the pharmacology, medicinal chemistry and drug delivery of potential new medicines. Sessions were held on: “Target diseases and targets for drugs”, “Target based medicinal chemistry”, “Bioavailability and chemistry”, “Targeting intracellular microbes”, “Alternative approaches and models”, and “New anti-infectives – how do we get there?”This symposium was organised by Simon Croft (LSHTM) and Mike Barrett (University of Glasgow) for the BSP, and David Alker (David Alker Associates) and Andrew Stachulski (University of Liverpool) for the Biological & Medicinal Chemistry sector of the RSC.

Eighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe

“…Here, we have shown that metagenomic approaches can document past infections. However, we have also recently shown that metagenomics can identify and characterize pathogens in contemporary samples 29 33 , so such approaches might soon also inform current and future infectious disease diagnosis and control.…”

Prevalence, species identification and genotyping Cryptosporidium from livestock and deer in a catchment in the Cairngorms with a history of a contaminated public water supply

“…Normally disease is self-limiting but the host may shed huge numbers of oocysts causing the infection to spread rapidly in calving areas and into the environment where they can remain infective for several years depending on environmental conditions. Livestock are well known as the main reservoirs for C. parvum [ 2 ] which is epidemiologically associated with zoonotic transmission [ 3 ] and are the species responsible for up to 50% of human cryptosporidiosis cases [ 4 ]. Infected neonatal calves tend to shed high concentrations of C. parvum oocysts [ 5 ] and in postcode sectors in Scotland which have a higher ratio of farms to humans, an increased rate of C. parvum infection in humans has been recorded [ 6 ].…”

Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome

“…The ease of developing resistance to both components of the nifurtimox / eflornithine combination therapy (NECT, the newest treatment to enter the clinic) [ 10 ] is also a major concern [ 11 , 12 ]. Moreover, due to its status as a neglected disease of declining incidence, the current drug discovery pipeline for HAT is far from robust [ 13 ]. Thus, development of new drugs remains a critical task.…”