Blocking SARS-CoV-2 Delta Variant (B.1.617.2) Spike Protein Receptor-Binding Domain Binding with the ACE2 Receptor of the Host Cell and Inhibiting Virus Infections Using Human Host Defense Peptide-Conjugated Graphene Quantum Dots.
Pramanik. Avijit A; Sharma. Poonam C PC; Patibandla. Shamily S; Gao. Ye Y; Ruppa-Kasani. Vinod V; Goli. Jagruti J; Kumar. Animesh A; Chatterjee. Abhirup A; Sinha. Sudarson Sekhar SS; Bates. John T JT; Bierdeman. Michael A MA; Tandon. Ritesh R; Ray. Paresh Chandra PC
Key Findings
- LL‑37‑conjugated graphene quantum dots bind the delta variant spike RBD with ~9 nM affinity, similar to ACE2’s natural binding
- Fluorescence quenching shows multiple binding sites (Hill coefficient ~2.6)
- In cell tests, LL‑37‑GQDs (and HNP1‑GQDs) fully blocked entry of delta‑variant pseudovirions, outperforming single‑peptide GQDs
Practical Outcomes
- This work is still at the laboratory stage and requires specialized nanomaterials, so it isn’t a protocol you can apply at home. It does highlight that LL‑37 can be part of antiviral nanotech designs, which may lead to future topical or inhaled treatments, but more development and safety testing are needed before any DIY use.
Summary
Scientists attached the natural antimicrobial peptide LL‑37 (and another peptide, HNP1) to tiny graphene quantum dots and found they can stick to the COVID‑19 delta variant’s spike protein, blocking it from attaching to the ACE2 receptor on cells and stopping a lab‑made virus from entering those cells.
Abstract
The emergence of double mutation delta (B.1.617.2) variants has dropped vaccine effectiveness against SARS-CoV-2 infection. Although COVID-19 is responsible for more than 5.4 M deaths till now, more than 40% of infected individuals are asymptomatic carriers as the immune system of the human body can control the SARS-CoV-2 infection. Herein, we report for the first time that human host defense neutrophil α-defensin HNP1 and human cathelicidin LL-37 peptide-conjugated graphene quantum dots (GQDs) have the capability to prevent the delta variant virus entry into the host cells via blocking SARS-CoV-2 delta variant (B.1.617.2) spike protein receptor-binding domain (RBD) binding with host cells' angiotensin converting enzyme 2 (ACE2). Experimental data shows that due to the binding between the delta variant spike protein RBD and bioconjugate GQDs, in the presence of the delta variant spike protein, the fluorescence signal from GQDs quenched abruptly. Experimental quenching data shows a nonlinear Stern-Volmer quenching profile, which indicates multiple binding sites. Using the modified Hill equation, we have determined <i>n</i> = 2.6 and the effective binding affinity 9 nM, which is comparable with the ACE2-spike protein binding affinity (8 nM). Using the alpha, beta, and gamma variant spike-RBD, experimental data shows that the binding affinity for the delta B.1.617.2 variant is higher than those for the other variants. Further investigation using the HEK293T-human ACE2 cell line indicates that peptide-conjugated GQDs have the capability for completely inhibiting the entry of delta variant SARS-CoV-2 pseudovirions into host cells via blocking the ACE2-spike protein binding. Experimental data shows that the inhibition efficiency for LL-37 peptide- and HNP1 peptide-attached GQDs are much higher than that of only one type of peptide-attached GQDs.
Study Information
pubmed
2022
2022-02-22T00:00:00.000Z
10.1021/acsomega.2c00113
15
27