Retrained Generic Antibodies Can Recognize SARS-CoV-2

Han, Yanxiao; McReynolds, Katherine D.

doi:10.1021/acs.jpclett.0c03615

Cited by 3 publications

(2 citation statements)

References 29 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Time-dependent RMSD for the pACE2–1, pACE2–2, and pACE2–3 conjugated dendrimers were calculated from R M S D α false( t j false) = ∑ α = 1 N α | r α ⃗ false( t j false) − r α ⃗ false( t 0 false) | 2 N α where N α is the number of atoms whose positions are being compared, r α 0em true⃗ ( t j ) is the position of atom α at time t j , and r α 0em true⃗ ( t 0 ) is the initial coordinate . The time-dependent RMSD was averaged over the last 50 ns of simulation time and is shown in Figure .…”

Section: Methodsmentioning

confidence: 99%

Dendrimer-Peptide Conjugates for Effective Blockade of the Interactions between SARS-CoV-2 Spike Protein and Human ACE2 Receptor

Jeong

Mickel

et al. 2022

Biomacromolecules

Self Cite

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID-19) pandemic has threatened the stability of global healthcare, which is becoming an endemic issue. Despite the development of various treatment strategies to fight COVID-19, the currently available treatment options have shown varied efficacy. Herein, we have developed an avidity-based SARS-CoV-2 antagonist using dendrimer-peptide conjugates (DPCs) for effective COVID-19 treatment. Two different peptide fragments obtained from angiotensin-converting enzyme 2 (ACE2) were integrated into a single sequence, followed by the conjugation to poly(amidoamine) (PAMAM) dendrimers. We hypothesized that the strong multivalent binding avidity endowed by dendrimers would help peptides effectively block the interaction between SARS-CoV-2 and ACE2, and this antagonist effect would be dependent upon the generation (size) of the dendrimers. To assess this, binding kinetics of the DPCs prepared from generation 4 (G4) and G7 PAMAM dendrimers to spike protein of SARS-CoV-2 were quantitatively measured using surface plasmon resonance. The larger dendrimer-based DPCs exhibited significantly enhanced binding strength by 3 orders of magnitude compared to the free peptides, whereas the smaller one showed a 12.8-fold increase only. An in vitro assay using SARS-CoV-2-mimicking microbeads also showed the improved SARS-CoV-2 blockade efficiency of the G7-peptide conjugates compared to G4. In addition, the interaction between the DPCs and SARS-CoV-2 was analyzed using molecular dynamics (MD) simulation, providing an insight into how the dendrimer-mediated multivalent binding effect can enhance the SARS-CoV-2 blockade. Our findings demonstrate that the DPCs having strong binding to SARS-CoV-2 effectively block the interaction between ACE2 and SARS-CoV-2, providing a potential as a high-affinity drug delivery system to direct anti-COVID payloads to the virus.

show abstract

Section: Methodsmentioning

confidence: 99%

Dendrimer-Peptide Conjugates for Effective Blockade of the Interactions between SARS-CoV-2 Spike Protein and Human ACE2 Receptor

Jeong

Mickel

et al. 2022

Biomacromolecules

Self Cite

View full text Add to dashboard Cite

show abstract

“…These T cells, as part of the adaptive immunity, recognize the viral antigens during an infection and promote cytokine release and cytotoxic activity inside the cell. At the same time, virus particles also recognize primary receptors and coreceptors present on T cells for gaining access into the body, such as in the case of HIV that recognize CD4 receptors and CXCR4 or CCR5 coreceptors for entry into CD4 + T cells . Therefore, the study of this direct interaction of the virus with the T cell is important.…”

mentioning

confidence: 99%

Persistent Correlation in Cellular Noise Determines Longevity of Viral Infections

Batra

Banerjee

Sharma

2022

J. Phys. Chem. Lett.

View full text Add to dashboard Cite

The slowly decaying viral dynamics, even after 2–3 weeks from diagnosis, is one of the characteristics of COVID-19 infection that is still unexplored in theoretical and experimental studies. This long-lived characteristic of viral infections in the framework of inherent variations or noise present at the cellular level is often overlooked. Therefore, in this work, we aim to understand the effect of these variations by proposing a stochastic non-Markovian model that not only captures the coupled dynamics between the immune cells and the virus but also enables the study of the effect of fluctuations. Numerical simulations of our model reveal that the long-range temporal correlations in fluctuations dictate the long-lived dynamics of a viral infection and, in turn, also affect the rates of immune response. Furthermore, predictions of our model system are in agreement with the experimental viral load data of COVID-19 patients from various countries.

show abstract

Retrained Generic Antibodies Can Recognize SARS-CoV-2

Han

McReynolds

2021

J. Phys. Chem. Lett.

Self Cite

View full text Add to dashboard Cite

The dramatic impact novel viruses can have on humans could be more quickly mitigated if generic antibodies already present in one’s system are temporarily retrained to recognize these viruses. This type of intervention can be administered during the early stages of infection, while a specific immune response is being developed. With this idea in mind, double-faced peptide-based boosters were computationally designed to allow recognition of SARS-CoV-2 by Hepatitis B antibodies. One booster face is made of ACE2-mimic peptides that can bind to the receptor binding domain (RBD) of SARS-CoV-2. The other booster face is composed of a Hepatitis B core-antigen, targeting the Hepatitis B antibody fragment. Molecular dynamics simulations revealed that the designed boosters have a highly specific and stable binding to both the RBD and the antibody fragment (AF). This approach can provide a cheap and efficient neutralization of emerging pathogens.

show abstract

Retrained Generic Antibodies Can Recognize SARS-CoV-2

Cited by 3 publications

References 29 publications

Dendrimer-Peptide Conjugates for Effective Blockade of the Interactions between SARS-CoV-2 Spike Protein and Human ACE2 Receptor

Dendrimer-Peptide Conjugates for Effective Blockade of the Interactions between SARS-CoV-2 Spike Protein and Human ACE2 Receptor

Persistent Correlation in Cellular Noise Determines Longevity of Viral Infections

Retrained Generic Antibodies Can Recognize SARS-CoV-2

Contact Info

Product

Resources

About