Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 11 6 2020 01 11 448 459 Fatemehsadat Jamzivar Department of Mycology, Pasteur Institute of Iran, Tehran, Iran Masoomeh Shams-Ghahfarokhi Department of Mycology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Mansoor Khoramizadeh School of Iranian Traditional Medicine, Iran University of Medical Sciences, Tehran, Iran Niloufar Yousefi Department of Mycology, Pasteur Institute of Iran, Tehran, Iran Mohammadhassan Gholami-Shabani Department of Mycology, Pasteur Institute of Iran, Tehran, Iran Mehdi Razzaghi-Abyaneh Department of Mycology, Pasteur Institute of Iran, Tehran, Iran 2019 06 24 2019 10 25 Over the past decades, the incidence of life-threatening fungal infections has increased dramatically in particular among patients with hampered immune function. Fungal infections cause around 1.5 million deaths annually, superior to malaria and tuberculosis. With respect to high toxicity, narrow spectrum of activity and drug resistance to current antifungals, there is an urgent need to discover novel leads from molecules of natural origin especially those derived from plants and microorganisms for antifungal drug discovery. Among antifungal drugs introduced into the clinic, those affecting ergosterol biosynthesis are still superior to other classes and the vital role of ergosterol in fungal growth and development. This review highlights current knowledge about available antifungal agents and further issues on antifungal drug discovery from compounds of natural origin which affect ergosterol biosynthesis. Special attention is made to the fungal sterol C24-methyltransferase (SMT), a crucial enzyme in ergosterol biosynthesis pathway as a novel target for rational drug design. https://ijm.tums.ac.ir/index.php/ijm/article/view/2231 https://ijm.tums.ac.ir/index.php/ijm/article/download/2231/1201