Target-Based Rational Improvement Strategies and Pitfalls in Leishmania Drug Discovery

Yash Gupta, Steven Goicoechea, Jesse Vance, Andres P. Trujillo, Akankcha Alok, Samuel K. Kwofie, Brijesh Rathi, Ravi Durvasula, Prakasha Kempaiah

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Worldwide parasite infection, especially Leishmania, is the most severe high morbidity and mortality issue. It is one of the leading protozoans parasitic agents responsible for causing the tropical disease leishmaniasis. In the seventh century BC, leishmaniasis comes into account by isolating leishmanial mitochondria DNA from Egyptian mummies circa 2000 BC. Multiple species are listed in this chapter, and their geographical distribution manifests typical diseases. Over 12 million people are currently affected, and around 350 million people are still likely to get infected by leishmaniasis. As leishmaniasis attacks mainly in rural area or the outskirts of cities, where healthcare facilities is a challenging job to hold on, it leads us to discover a therapeutic approach with cost-effective and easy access to the need with significant diagnosis and treatment of the disease. Unfortunately, there is no potential theranostics against Leishmania due to the clinical and acquired resistance. Thus, we must find new a weapon or strategies, such as drug repurposing by using drugs already available for other diseases. Several antileishmanial drugs are available for treating leishmaniasis, including repurposed drugs. Recently, several alternative therapies have provided a novel approach to drug discovery through rational improvement, including target identification and modeling, compound screening and ligand structure validation by virtual screening against the novel target.

Original languageEnglish
Title of host publicationNatural Product Based Drug Discovery against Human Parasites
Subtitle of host publicationOpportunities and Challenges
PublisherTaylor and Francis
Pages329-384
Number of pages56
ISBN (Electronic)9789811996054
ISBN (Print)9789811996047
DOIs
Publication statusPublished - 1 Jan 2023

Keywords

  • Drug discovery
  • Hit to lead
  • Rational improvement
  • Target-based
  • Therapeutic landscape

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