Article ; Online: Identification of a druggable site on GRP78 at the GRP78-SARS-CoV-2 interface and virtual screening of compounds to disrupt that interface.
Journal of computer-aided molecular design
2024 Volume 38, Issue 1, Page(s) 6
Abstract: SARS-CoV-2, the virus that causes COVID-19, led to a global health emergency that claimed the lives of millions. Despite the widespread availability of vaccines, the virus continues to exist in the population in an endemic state which allows for the ... ...
| Abstract | SARS-CoV-2, the virus that causes COVID-19, led to a global health emergency that claimed the lives of millions. Despite the widespread availability of vaccines, the virus continues to exist in the population in an endemic state which allows for the continued emergence of new variants. Most of the current vaccines target the spike glycoprotein interface of SARS-CoV-2, creating a selection pressure favoring viral immune evasion. Antivirals targeting other molecular interactions of SARS-CoV-2 can help slow viral evolution by providing orthogonal selection pressures on the virus. GRP78 is a host auxiliary factor that mediates binding of the SARS-CoV-2 spike protein to human cellular ACE2, the primary pathway of cell infection. As GRP78 forms a ternary complex with SARS-CoV-2 spike protein and ACE2, disrupting the formation of this complex is expected to hinder viral entry into host cells. Here, we developed a model of the GRP78-Spike RBD-ACE2 complex. We then used that model together with hot spot mapping of the GRP78 structure to identify the putative binding site for spike protein on GRP78. Next, we performed structure-based virtual screening of known drug/candidate drug libraries to identify binders to GRP78 that are expected to disrupt spike protein binding to the GRP78, and thereby preventing viral entry to the host cell. A subset of these compounds has previously been shown to have some activity against SARS-CoV-2. The identified hits are starting points for the further development of novel SARS-CoV-2 therapeutics, potentially serving as proof-of-concept for GRP78 as a potential drug target for other viruses. |
|---|---|
| MeSH term(s) | Humans ; SARS-CoV-2 ; COVID-19 ; Angiotensin-Converting Enzyme 2 ; Endoplasmic Reticulum Chaperone BiP ; Vaccines ; Spike Glycoprotein, Coronavirus |
| Chemical Substances | spike protein, SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Endoplasmic Reticulum Chaperone BiP ; Vaccines ; Spike Glycoprotein, Coronavirus |
| Language | English |
| Publishing date | 2024-01-24 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 808166-9 |
| ISSN | 1573-4951 ; 0920-654X |
| ISSN (online) | 1573-4951 |
| ISSN | 0920-654X |
| DOI | 10.1007/s10822-023-00546-w |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 2625: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.