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Updated: Oct 22, 2025
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Identification of Niemann-Pick C1 protein as a potential novel SARS-CoV-2 intracellular target
Isabel García-Dorival1, Miguel Ángel Cuesta-Geijo2, Lucía Barrado-Gil2
1Dpt. Biotecnología, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ctra. de la Coruña km 7.5, 28040, Madrid, Spain.
Abstract:
Niemann-Pick type C1 (NPC1) receptor is an endosomal membrane protein that regulates intracellular cholesterol traffic. This protein has been shown to play an important role for several viruses. It has been reported that SARS-CoV-2 enters the cell through plasma membrane fusion and/or endosomal entry upon availability of proteases. However, the whole process is not fully understood yet and additional viral/host factors might be required for viral fusion and subsequent viral replication. Here, we report a novel interaction between the SARS-CoV-2 nucleoprotein (N) and the cholesterol transporter NPC1. Furthermore, we have found that some compounds reported to interact with NPC1, carbazole SC816 and sulfides SC198 and SC073, were able to reduce SARS-CoV-2 viral infection with a good selectivity index in human cell infection models. These findings suggest the importance of NPC1 for SARS-CoV-2 viral infection and a new possible potential therapeutic target to fight against COVID-19.
Insights
Researchers discovered that SARS-CoV-2 interacts with the NPC1 protein, crucial for cholesterol transport. Compounds targeting NPC1 reduced viral infection, suggesting NPC1 as a potential therapeutic target for COVID-19.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Niemann-Pick type C1 (NPC1) is an endosomal protein regulating cholesterol.
- NPC1 is implicated in the life cycle of various viruses.
- SARS-CoV-2 entry mechanisms, including NPC1's role, require further elucidation.
Purpose of the Study:
- To investigate the interaction between SARS-CoV-2 and NPC1.
- To explore NPC1 as a potential target for antiviral therapies against SARS-CoV-2.
Main Methods:
- Investigated the interaction between SARS-CoV-2 nucleoprotein (N) and NPC1.
- Tested NPC1-targeting compounds (SC816, SC198, SC073) for antiviral activity.
- Assessed viral infection reduction and selectivity index in human cell models.
Main Results:
- A novel interaction between SARS-CoV-2 nucleoprotein (N) and NPC1 was identified.
- Compounds targeting NPC1 demonstrated significant reduction in SARS-CoV-2 infection.
- The tested compounds exhibited a good selectivity index in cellular models.
Conclusions:
- NPC1 plays a significant role in SARS-CoV-2 infection.
- NPC1 represents a promising therapeutic target for developing novel COVID-19 treatments.
