The Niemann-Pick type C1 (NPC1) is a late-endosomal membrane protein required for transport of cholesterol into the cells ( Li et al., 2016). An example of this is the Hepatitis C virus (HCV), which uses the cellular Niemann-Pick C1-like 1 protein (NPC1L1), an homologous protein to NPC1 acting as a transmembrane-domain cell surface cholesterol-sensing receptor that is expressed on the apical surface of intestinal enterocytes and human hepatocytes ( Sainz et al., 2012, Scott and Ioannou, 2004).
Several viruses interact with proteins related to the cholesterol transport. Considering that SARS-CoV-2 may enter the cells by endocytosis, it would be partially acid pH-dependent and should exit endosomes by membrane fusion to start replication ( Tharappel et al., 2020).
In fact, the inhibition of both alternatives is necessary for full inhibition of SARS-CoV-2 entry ( Hoffmann et al., 2020 Ou et al., 2020).
But, similarly to SARS-CoV-1, SARS-CoV-2 virus can also enter via endosomes after binding ACE2 receptor and subsequent cathepsin L processing ( Inoue et al., 2007 Wang et al., 2008). A better understanding of the biology of SARS-CoV-2 is vital in order to develop effective therapeutics.Ī key step in the biology of SARS-CoV-2 is the cell entry mechanism upon interaction with the angiotensin-converting enzyme 2 (ACE2) receptor at the plasma membrane, which mediates fusion of membranes ( Lan et al., 2020 Shang et al., 2020a, 2020b Wang et al., 2008 Zhou et al., 2020). These facts highlight the urgent need for developing efficient therapeutics against SARS-CoV-2 since there are only a few licensed treatments available ( Indari et al., 2021). The current coronavirus disease 19 (COVID-19) pandemic, caused by the emerging and pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected more than 170 millions of people worldwide and constitutes one of the greatest challenges in this century due to a great loss of lives, more than four millions up to date (WHO Coronavirus dashboard July 8, 2021) ( WHO, 2021).