Resources
In: Gender and development, Band 31, Heft 1, S. 285-300
ISSN: 1364-9221
9 Ergebnisse
Sortierung:
In: Gender and development, Band 31, Heft 1, S. 285-300
ISSN: 1364-9221
In: Gender and development, Band 31, Heft 2-3, S. 725-747
ISSN: 1364-9221
In: Gender and development, Band 30, Heft 3, S. 785-808
ISSN: 1364-9221
SSRN
In: Gender and development, Band 31, Heft 1, S. 1-10
ISSN: 1364-9221
In: Energy economics, Band 133, S. 107521
ISSN: 1873-6181
In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 195, S. 110481
ISSN: 1090-2414
In: Gender and development, Band 31, Heft 2-3, S. 307-321
ISSN: 1364-9221
In: PNAS nexus, Band 1, Heft 5
ISSN: 2752-6542
Abstract
As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key toward sustenance. Here, we identify an evolutionarily conserved "Ex3Lx6L" ("E-L-L") motif present within the HR2 domain of all human and nonhuman coronavirus spike (S) proteins that play a crucial role in stabilizing its postfusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this "E-L-L" motif and impedes the formation of 6-HB, thus effectively inhibiting SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy in blocking S protein-mediated viral entry, mutations within the "E-L-L" motif rendered the protein completely resistant to the drug, establishing its specificity toward this motif. Our data demonstrate that posaconazole restricts early stages of infection through specific inhibition of membrane fusion and viral genome release into the host cell and is equally effective toward all major variants of concerns of SARS-CoV-2, including Beta, Kappa, Delta, and Omicron. Together, we show that this conserved essential "E-L-L" motif is an ideal target for the development of prophylactic and therapeutic interventions against SARS-CoV-2.