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. 2022 Apr 1;12:5562. doi: 10.1038/s41598-022-09588-w

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Schematic of the endogenous cholesterol biosynthetic pathway. Cholesterol synthesis involves a complex series of enzymatic reactions from the 2 carbon acetyl CoA to 27 carbon cholesterol. De novo cholesterol biosynthesis takes place in the ER membrane, also the site of HCV replication. The rate limiting step is the activity of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase and the production of mevalonate. The post mevalonate intermediate geranylgeranyl is required for HCV replication. Geranyl that is not used in prenylation is converted to farnesyl and subsequently to squalene, then to lanosterol¹⁸. From lanosterol, cholesterol biosynthesis can proceed by two routes: via a desmosterol intermediate (Bloch pathway), or via a lathosterol intermediate (Kandutsch-Russel pathway), with flux across the two pathways regulated by ∆24 dehydrocholesterol reductase (DHCR24).