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COVID-19 Treatment
by Jefferson
A Novel Drug Target in Prostate Cancer Emerges as Potential Target for Coronavirus Treatment
At the beginning of last year – and just a few months before the novel coronavirus was reported in the United States – Felix Kim, PhD, was awarded an R01 research grant from the National Cancer Institute (NCI) for his project, “Multifunctional regulation of prostate cancer metabolism by Sigma1 modulators.”
Kim, an Associate Professor of Cancer Biology at the Sidney Kimmel Cancer Center (SKCC), aims to define how Sigma1 (also known as sigma-1 receptor) – a unique, pharmacologically controllable scaffolding protein that is aberrantly expressed in prostate cancer and required for tumor growth – regulates metabolic processes essential for prostate cancer proliferation and disease progression, and to discover and develop a novel class of therapeutic agents that target Sigma1 in order to treat advanced prostate cancer.
“By targeting Sigma1, we propose a new approach to restricting metabolic processes that drive the proliferation of lethal prostate cancer,” Kim said. “This approach simultaneously targets multiple growth pathways in prostate cancer and may circumvent resistance mechanisms that invariably emerge with the sequential use of current standard of care therapeutic agents.”
Kim has been studying Sigma1 in cancer biology and Sigma1 pharmacology for over 10 years; however, he had previously worked on human viruses for more than a decade. “My PhD thesis was focused on dissecting key determinants of viral entry into host cells and also on understanding how new viruses emerge as a result of interspecies infections,” he explained.
In mid-March last year, Kim came across a preprint report from a group of researchers at the University of California, San Francisco, in which they identified 69 existing drugs and experimental compounds that could potentially be repurposed to treat COVID-19.
“This was based on a protein interaction screen wherein they identified a number of cellular proteins that physically bind to key SARS-CoV-2/ COVID-19 viral proteins. They ser-
endipitously found Sigma1 among them, and this piqued my interest,” Kim said. “So, I took a closer look at whether I could make sense of how Sigma1 might be involved in SARS-CoV-2/COVID-19 infection.”
Coronaviruses replicate by co-opting the machinery inside the cells of the infected host. When the virus infects a host, it remains completely dependent on this cellular machinery in order to replicate and spread. Sigma1 is an important part of the cellular machinery, helping to regulate the production, processing, and quality control of essential proteins and lipids, particularly under conditions of stress, such as viral infection. This led Kim to hypothesize that targeting Sigma1 might prevent the virus from co-opting the cellular machinery, thus blocking COVID-19 replication and dissemination.
Kim, in collaboration with Holly Ramage, PhD, Assistant Professor of Microbiology and Immunology at Thomas Jefferson University, plans to establish whether Sigma1 is a valid therapeutic target for SARS-CoV-2 and related viruses and to evaluate whether a series of novel compounds originally proposed as anti-cancer therapeutic agents can be used to target Sigma1 in a range of viral infections. Additionally, Kim and Ramage are looking to identify established drugs that bind Sigma1 that can potentially be repurposed as antiviral therapies for COVID-19 infection.
Felix Kim, PhD Associate Professor, Department of Cancer Biology Associate Director of Training & Education, SKCC
