title: Potential of marine natural products against drug-resistant fungal, viral, and parasitic infections.
abstract: Antibiotics have revolutionised medicine in many aspects, and their discovery is considered a turning point in human history. However, the most serious consequence of the use of antibiotics is the concomitant development of resistance against them. The marine environment has proven to be a very rich source of diverse natural products with significant antibacterial, antifungal, antiviral, antiparasitic, antitumour, anti-inflammatory, antioxidant, and immunomodulatory activities. Many marine natural products (MNPs)-for example, neoechinulin B-have been found to be promising drug candidates to alleviate the mortality and morbidity rates caused by drug-resistant infections, and several MNP-based anti-infectives have already entered phase 1, 2, and 3 clinical trials, with six approved for usage by the US Food and Drug Administration and one by the EU. In this Review, we discuss the diversity of marine natural products that have shown in-vivo efficacy or in-vitro potential against drug-resistant infections of fungal, viral, and parasitic origin, and describe their mechanism of action. We highlight the drug-like physicochemical properties of the reported natural products that have bioactivity against drug-resistant pathogens in order to assess their drug potential. Difficulty in isolation and purification procedures, toxicity associated with the active compound, ecological impacts on natural environment, and insufficient investments by pharmaceutical companies are some of the clear reasons behind market failures and a poor pipeline of MNPs available to date. However, the diverse abundance of natural products in the marine environment could serve as a ray of light for the therapy of drug-resistant infections. Development of resistance-resistant antibiotics could be achieved via the coordinated networking of clinicians, microbiologists, natural product chemists, and pharmacologists together with pharmaceutical venture capitalist companies.
authors.affiliation: Department of Botany II, Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Würzburg, Germany; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt. Electronic address: usama.ramadan@uni-wuerzburg.de.
authors.forename: Usama Ramadan
authors.initials: UR
authors.lastname: Abdelmohsen
authors.affiliation: Department of Botany II, Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Würzburg, Germany; Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Srikkanth
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Tobias A
authors.initials: TA
authors.lastname: Oelschlaeger
authors.affiliation: Natural Products Support Group, Leidos Biomedical Research Inc, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Grkovic
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD, Australia.
authors.forename: Ngoc B
authors.initials: NB
authors.lastname: Pham
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD, Australia.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
authors.affiliation: Department of Botany II, Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Würzburg, Germany; GEOMAR Helmholtz Centre for Ocean Research, RD3 Marine Microbiology, Kiel, Germany; Christian-Albrechts University of Kiel, Kiel, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hentschel
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D001688:Biological Products / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D025141:Drug Resistance, Fungal; D015507:Drugs, Investigational / Q000627:therapeutic use; D006801:Humans; D008386:Marine Biology; D009181:Mycoses; D010272:Parasitic Diseases; D014481:United States; D014777:Virus Diseases
chemical_list: D000890:Anti-Infective Agents; D001688:Biological Products; D015507:Drugs, Investigational