Abstract
Lipid rafts are functional membrane microdomains containing sphingolipids, including gangliosides, and cholesterol. These regions are characterized by highly ordered and tightly packed lipid molecules. Several studies revealed that lipid rafts are involved in life cycle of different viruses, including coronaviruses. Among these recently emerged the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The main receptor for SARS-CoV-2 is represented by the angiotensin-converting enzyme-2 (ACE-2), although it also binds to sialic acids linked to host cell surface gangliosides. A new type of ganglioside-binding domain within the N-terminal portion of the SARS-CoV-2 spike protein was identified. Lipid rafts provide a suitable platform able to concentrate ACE-2 receptor on host cell membranes where they may interact with the spike protein on viral envelope. This review is focused on selective targeting lipid rafts components as a strategy against coronavirus. Indeed, cholesterol-binding agents, including statins or methyl-β-cyclodextrin (MβCD), can affect cholesterol, causing disruption of lipid rafts, consequently impairing coronavirus adhesion and binding. Moreover, these compounds can block downstream key molecules in virus infectivity, reducing the levels of proinflammatory molecules [tumor necrosis factor alpha (TNF-α), interleukin (IL)-6], and/or affecting the autophagic process involved in both viral replication and clearance. Furthermore, cyclodextrins can assemble into complexes with various drugs to form host–guest inclusions and may be used as pharmaceutical excipients of antiviral compounds, such as lopinavir and remdesivir, by improving bioavailability and solubility. In conclusion, the role of lipid rafts-affecting drugs in the process of coronavirus entry into the host cells prompts to introduce a new potential task in the pharmacological approach against coronavirus.
Highlights
Maurizio Sorice 1*, Roberta Misasi 1, Gloria Riitano 1, Valeria Manganelli 1, Stefano Martellucci 2, Agostina Longo 1, Tina Garofalo 1 and Vincenzo Mattei 2
The main receptor for SARS-CoV-2 is represented by the angiotensin-converting enzyme-2 (ACE-2), it binds to sialic acids linked to host cell surface gangliosides
A guanine derivative approved for treating Hepatitis C Virus (HCV) and respiratory syncytial virus (RSV) that has been evaluated in patients with SARS and MERS, but its side effects such as anemia may be severe at high doses and whether it offers sufficient potency against 2019-nCoV is uncertain
Summary
Maurizio Sorice 1*, Roberta Misasi 1, Gloria Riitano 1, Valeria Manganelli 1, Stefano Martellucci 2, Agostina Longo 1, Tina Garofalo 1 and Vincenzo Mattei 2. Several studies revealed that lipid rafts are involved in life cycle of different viruses, including coronaviruses Among these recently emerged the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Cholesterol-binding agents, including statins or methyl-β-cyclodextrin (MβCD), can affect cholesterol, causing disruption of lipid rafts, impairing coronavirus adhesion and binding These compounds can block downstream key molecules in virus infectivity, reducing the levels of proinflammatory molecules [tumor necrosis factor alpha (TNF-α), interleukin (IL)-6], and/or affecting the autophagic process involved in both viral replication and clearance. Several coronaviruses may enter directly from the cell surface, when receptor-bound viruses are treated with proteases activating S proteins This process generates homotrimers on the virion surface triggering the early fusion pathway. The SARS-CoV-2 infection is currently underway and is exponentially developing especially in USA, Europe, South America, Russia, and India, recording more than 2,000,000 deaths
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.