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Herein, we fabricate host-directed virus-mimicking particles (VMPs) to block the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells through competitive inhibition enabled by their interactions with the angiotensin-converting enzyme 2 (ACE2) receptor. A microfluidic platform is developed to fabricate a lipid core of the VMPs with a narrow size distribution and a low level of batch-to-batch variation. The resultant solid lipid nanoparticles are decorated with an average of 231 or 444 Spike S1 RBD protrusions mimicking either the original SARS-CoV-2 or its delta variant, respectively. Compared with that of the nonfunctionalized core, the cell uptake of the functionalized VMPs is enhanced with ACE2-expressing cells due to their strong interactions with the ACE2 receptor. The fabricated VMPs efficiently block the entry of SARS-CoV-2 pseudovirions into host cells and suppress viral infection. Overall, this study provides potential strategies for preventing the spread of SARS-CoV-2 or other coronaviruses employing the ACE2 receptor to enter into host cells.
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http://dx.doi.org/10.1021/acs.nanolett.3c04430 | DOI Listing |
Phys Chem Chem Phys
September 2025
School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, P. R. China.
The COVID-19 pandemic remains a global health crisis, with successive SARS-CoV-2 variants exhibiting enhanced transmissibility and immune evasion. Notably, the Omicron variant harbors extensive mutations in the spike protein's receptor-binding domain (RBD), altering viral fitness. While temperature is a critical environmental factor modulating viral stability and transmission, its molecular-level effects on variant-specific RBD-human angiotensin-converting enzyme 2 (hACE2) interactions remain underexplored.
View Article and Find Full Text PDFAntiviral Res
September 2025
Department of Immunology and Pathogen Biology, Key Laboratory of Pathogen and Host-Interactions, Ministry of Education, School of Medicine, Tongji University, Shanghai 200331, China. Electronic address:
DMBT1 is a large scavenger receptor cysteine rich (SRCR) B protein that has been reported as a tumor suppressor gene and a co-receptor for HIV-1 infection. Here we found DMBT1 is a major mucosal protein bound to SARS-CoV-2. Overexpression of DMBT1 in 293T cells may enhanced infection by SARS-CoV-2 in ACE2 dependent manner.
View Article and Find Full Text PDFA key goal of vaccinology is to train the immune system to combat current pathogens while simultaneously preparing it for future evolved variants. Understanding factors contributing to anticipatory breadth, wherein affinity maturation against an ancestral strain yields neutralization capacity against evolved variants, is therefore of great importance. Here, we investigated the mechanism of anticipatory breadth development in a public antibody family targeting the functionally restricted ACE2 binding site on SARS-CoV-2.
View Article and Find Full Text PDFVet Microbiol
August 2025
College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. Electronic address:
Transmissible gastroenteritis virus (TGEV) is one of the major pathogen causing swine diarrhea, inducing acute severe atrophic enteritis and lethal watery diarrhea in neonatal piglets with up to 100 % mortality, resulting in significant economic losses to the swine industry. Angiotensin-converting enzyme 2 (ACE2) is known as an invasion receptor for SARS-CoV-2, but its role in TGEV infection remains unclear, and the current understanding of TGEV infection mechanisms is incomplete. In this study, we identified an important role for porcine ACE2 (pACE2) in TGEV infection.
View Article and Find Full Text PDFJ Virol
September 2025
School of Life and Environmental Sciences, The University of Sydney, Camperdown, New South Wales, Australia.
Unlabelled: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates canonical cell entry via ACE2 and has also been implicated as an activator of a diverse range of signaling pathways. Here, we present evidence that the RGD (Arg-Gly-Asp) motif within the receptor-binding domain (RBD) of the S1 fragment of the S protein induces TGF-β cytokine expression. RGD peptides are well characterized as ligands for a subset of integrin complexes primarily containing α5 and αV subunits.
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