Trends of Pharmaceutical Design of Endophytes as Anti-infective

Abstract

: Plant-endophyte associations represent an inexhaustible source of novel metabolites, exhibiting significance in environment, agriculture and pharmaceutical perspectives. The global outbreak of life threatening diseases necessitate a need for a more targeted approach through efficient drug-discovery programs. In recent times, endophytes as “bio-factories” have been extensively explored for the production of novel, bioactive metabolites demonstrating therapeutic properties. Resources in computational biology co-integrated with combinational chemistry have made significant contributions in this field, aiding in the discovery and screening of potential “drug-like” molecules from endophytes. The review provides a meta-analysis of bioactive metabolite production from endophytes, extensively discussing the bio-prospection of natural products for pharmaceutical applications. In light of the emerging importance of endophytes as anti-infective agents, an exploration of the pharmaceutical design of novel chemical entities and analogues has enabled efficient and cost-effective drug discovery programs. However, bottlenecks in endophyte biology and research require a better understanding of endophyte dynamics and mechanism of bioactive metabolite production towards a sustainable drug discovery program.

Endophytic Fungi: Key Insights, Emerging Prospects, and Challenges in Natural Product Drug Discovery

“…Plant-associated endophytes have gained significant momentum in bio-prospection and isolation of bioactive metabolites with multi-faceted attributes. In this direction, literature reviews have provided key insights into the existing and emerging significance of endophytes in drug discovery and research-a few articles worth mentioning include Discussion on biodiversity of endophytes and its exploitation in drug discovery [1], Bioactive metabolites, and their pharmaceutical design in drug development [2], Emerging roles and applications of actinomycetes endophytes [13], Chemical ecology of endophytes and its role in bioactive metabolite production [43], The process of horizontal gene transfer and its implications in the transfer of novel traits in production of bioactive metabolites [56], and comprehensive insight on the diverse metabolites produced by fungal endophytes and their biological functions, among others. The present review on fungal endophytes provides a detailed insight into the existing and emerging prospects of fungal endophytes as "novel candidates" in drug discovery and research and how the different yield enhancement strategies can be adopted to address the associated bottlenecks and enhance bioactive metabolite production.…”

“…Endophytes represent biological reservoirs of novel natural products, opening new avenues in the frontiers of drug discovery. Plant-associated microorganisms that colonize the internal tissues of all plant species are gaining momentum as key targets for bio-prospection in the search for novel chemical entities [1,2]. The discovery of the acclaimed anticancer drug paclitaxel accelerated research on endophytic biology and yielded prospective "drug candidates" with antimicrobial, immunosuppressant, antioxidant, and anti-neurodegenerative functions [1][2][3].…”

“…Plant-associated microorganisms that colonize the internal tissues of all plant species are gaining momentum as key targets for bio-prospection in the search for novel chemical entities [1,2]. The discovery of the acclaimed anticancer drug paclitaxel accelerated research on endophytic biology and yielded prospective "drug candidates" with antimicrobial, immunosuppressant, antioxidant, and anti-neurodegenerative functions [1][2][3]. Currently, the impact of natural products in clinical applications cannot be underestimated [4], with the pharmaceutical sector adopting highthroughput approaches to screen plant secondary metabolites as potential lead molecules.…”

“…With the emerging threat of drug-resistant microbes and antimicrobial resistance (AMR), it has become essential to discover novel antimicrobials to counter AMR. However, the low pace of discovery and indiscriminate use of the existing antibiotics have further necessitated the exploration of novel antimicrobial entities to compensate for the drying drug pipeline [2,[6][7][8]. The rich yet less-explored diversity of endophytic entities and their considerable potential to impact the pharmaceutical industry have facilitated the discovery of secondary metabolites of therapeutic significance (Figure 1.…”

“…icroorganisms 2022, 10, 360 2 of 48 further necessitated the exploration of novel antimicrobial entities to compensate for the drying drug pipeline [2,[6][7][8]. The rich yet less-explored diversity of endophytic entities and their considerable potential to impact the pharmaceutical industry have facilitated the discovery of secondary metabolites of therapeutic significance (Figure 1.…”