viral protease, RNA polymerase and other nonstructural genes. Two agents—boceprevir by Merck and telaprevir by Vertex Pharmaceuticals—both inhibitors of NS3 protease were approved for use on May 13, 2011 and May 23, 2011 respectively. A possible association between low Vitamin D levels and a poor response to treatment has been reported. In vitro work has shown that vitamin D may be able to reduce viral replication. While this work looks promising the results of clinical trials are pending. However, it has been proposed that vitamin D supplementation is important in addition to standard treatment, in order to enhance treatment response. Naringenin, a flavonoid found in grapefruit and other fruits and herbs, has been shown to block the assembly of intracellular infectious viral particles without affecting intracellular levels of the viral RNA or protein. Other agents that are under investigation include nucleoside and nucleotide analogue inhibitors and non-nucleoside inhibitors of the RNA-dependent RNA polymerase, inhibitors of NSP5A, and host-targeted compounds such as cyclophilin inhibitors and silibinin. Sofosbuvir for use against chronic hepatitis C infection was approved by the FDA on December 6, 2013. It has been reported to be the first drug that has demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon. On November 22, the FDA approved simeprevir for use in combination with peginterferon-alfa and ribavirin. Simeprevir has been approved in Japan for the treatment of chronic hepatitis C infection, genotype 1. There is also current experimental research on non drug related therapies. Oxymatrine, for example, is a root extract found in the continent of Asia that has been reported to have antiviral activity against HCV in cell cultures and animal studies. Small and promising human trials have shown beneficial results and no serious side effects, but they were too small to generalize conclusions. On October 5th, 2020, it was announced that Harvey J. Alter, Michael Houghton, and Charles M. Rice had been awarded the 2020 Nobel Prize in Physiology or Medicine for the discovery of HCV. See also Blood-borne disease Cancer virus Discovery and development of NS5A inhibitors HCV IRES Hepatitis C virus stem-loop VII Hepatitis C virus 3′X element Hepatitis C virus (HCV) cis-acting replication element (CRE) Sexually transmitted infection References External links Academic articles about the HCV six genotypes Clodovero Ferri HCV Sequence and Immunology Databases at Los Alamos National Laboratory Virus Pathogen Database and Analysis Resource