Inspired by Nature: Towards Novel Anti-infective Agents

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Background

Natural products remain a source of numerous chemical entities, providing a much deeper coverage of the chemical space when compared to all available compound libraries. Their main advantage resides on the scaffold complexity and diversity which is the keystone to the wide range of biological activities found. Furthermore, as the large majority of the desired scaffolds is difficult to synthesize, isolation from their natural sources are still the best approach to obtain them. This way, the identification of bioactive extracts, either derived from plants, microorganisms or marine products, followed by isolation of active molecules and further chemical modification, allows researchers to develop custom-based libraries that can be later used to unveil the molecular mechanisms by which these molecular entities exert their activities in a given biological target.

By investing in the discovery of novel compounds and understanding how a particular mechanism can be blocked, or enhanced, current knowledge can progress and previous applications expand exponentially when a single library of compounds is assessed against multiple biological targets. Since big pharma companies have been dropping most of their anti-infective drug development pipelines, repurposing of novel or existing libraries of compounds against novel targets has been gaining an overwhelming importance, especially in the antibacterial, antiparasitic and antiviral fields. One of such libraries is the Shared Platform for Antibiotic Research and Knowledge (SPARK), created by The Pew Charitable Trusts, integrating chemical and biological data from published studies as well as previously unpublished data to assist in speeding up antibiotic development. Thus, the same approach can be used for the identification of novel antimicrobial, antiparasitic or antiviral molecules.

Currently, the increasing number of reports on antibiotic resistance are a major concern for worldwide healthcare systems. Together with the lack of effective alternatives for many neglected tropical diseases in developing countries and with the lack of new therapeutic agents able to prevent viral outbreaks, continuous chemical modifications of known scaffolds remains as an attractive approach to further increase potency and selectivity towards a specific target, especially when guided by preliminary structure-activity relationships obtained from a small pool of derivatives. Therefore, screening of such custom libraries against new targets is foreseen as a valuable tool to provide new hits against other currently undruggable targets or to identify new organisms sensitive to its biological range of activities.

Within this Research Topic, we aim to disclose the latest research in bioactivity-guided identification, isolation and characterization of novel scaffolds from natural sources on the field of anti-infective agents. We welcome the below sub-Topic themes, but not limited to:

● New antibiotics against the global priority list of antibiotic-resistant bacteria
● Characterization of novel scaffolds and bioactivities from marine products
● Novel hits against malaria or other tropical neglected diseases
● Rational studies towards identification and/or optimization of new bioactive molecules against viral pathogens
● Nature-inspired hemisynthesis or total synthesis methodological development
● Novel structure-activity relationships, experimental or in silico, derived from custom bioactive libraries
● Bioactivities of plants, fungi or microbial extracts and identification of major active components


Topic Editor, Daniel da Silva, is employed by Unilever. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

Keywords: Herbal extracts, bioactive molecules, anti-infective agents, chemical libraries, hemisynthesis

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