Antigen Spatial-Matching Polyaptamer Nanostructure to Block Coronavirus Infection and Alleviate Inflammation

Nanoscience Infectious Diseases Chemistry Immunology Bioengineering Microbiology Life Sciences Medicine
antigen spatial matching polyaptamer coronavirus inflammation nanostructure antiviral anti-inflammatory

Academic Background

In recent years, multiple outbreaks caused by coronaviruses have occurred globally, such as SARS (Severe Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome), and COVID-19 (Novel Coronavirus Pneumonia). These pandemics have not only posed a serious threat to human health but also exposed the inadequacy of emergency response strategies against sudden coronavirus infections. Coronavirus infections are often accompanied by pulmonary inflammatory responses, so, in addition to inhibiting viral infection, alleviating inflammation has become a key challenge in treatment. Although traditional antibody therapies are effective, they have long development cycles and are difficult to keep up with the rapid mutation of viruses. Furthermore, antibody-dependent enhancement (ADE) may also result in unsatisfactory therapeutic outcomes. Therefore, it is especially important to develop a therapeutic strategy that can quickly respond to emerging coronavirus infections, while simultaneously exhibiting antiviral and anti-inflammatory functions.

Based on this background, researchers have proposed a novel “Antigen Spatial-Matching Polyaptamer (ASM-PAPT)” nanostructure, aiming to enhance the binding potency of aptamers by precisely matching the spike proteins (S proteins) on the coronavirus surface, thereby blocking viral infection. At the same time, this nanostructure is also loaded with anti-inflammatory drugs in order to achieve a synergistic antiviral and anti-inflammatory effect.

Source of the Paper

This study was jointly performed by Jingqi Chen, Yuqing Li, Xueliang Liu, and many other scholars, with the research team coming from the Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, the Institute of Functional Nano & Soft Materials, Soochow University, and other institutions. The paper was published in the journal Chem on April 10, 2025, under the title “Antigen Spatial-Matching Polyaptamer Nanostructure to Block Coronavirus Infection and Alleviate Inflammation”.

Research Process and Results

1. Preparation and Characterization of the Antigen Spatial-Matching Polyaptamer Nanostructure

The researchers first designed a novel polyaptamer nanostructure, generating long-chain DNA containing multiple aptamer units via rolling circle amplification (RCA). By precisely controlling the linkage distance between aptamers and the size of the nanostructure, the researchers successfully fabricated a polyaptamer nanostructure that spatially matches with the S protein of coronavirus. To verify the successful synthesis of the nanostructure, they characterized it with polyacrylamide gel electrophoresis (PAGE) and transmission electron microscopy (TEM). Results showed that the nanostructure presented a sea-urchin-like morphology with a size of approximately 200–300 nanometers.

2. Verification of the Antiviral Capability of the Polyaptamer Nanostructure

To assess the antiviral effect of the polyaptamer nanostructure, the researchers used a SARS-CoV-2 pseudovirus (PSV) as a model and measured the binding affinity between the nanostructure and pseudovirus by microscale thermophoresis (MST). The results showed that the polyaptamer nanostructure with a size of 500 nm exhibited the strongest binding affinity, having a dissociation constant (Kd) of 531 fM, which was 200 times lower than that of the monovalent aptamer. In addition, by using molecular dynamics (MD) simulations, the researchers optimized the linkage distance between aptamers, and found that when the linkage distance was 30 nucleotides (nt), the polyaptamer could simultaneously bind to the three receptor-binding domains (RBD) of the S protein trimer, thereby effectively blocking viral infection.

3. Verification of the Anti-Inflammatory Capability of the Polyaptamer Nanostructure

To enhance the anti-inflammatory effect of the nanostructure, the researchers loaded the nanostructure with the natural antioxidant tannic acid (TA). Through free radical scavenging experiments, they confirmed the antioxidative capability of TA; results showed that a TA-loaded nanostructure at 0.8 μM could clear nearly 80% of DPPH free radicals. Furthermore, cellular experiments demonstrated the role of TA in suppressing inflammatory responses. Results showed that TA significantly downregulated the expression of inflammatory factors TNF-α, IL-1β, and IL-6, and inhibited macrophage polarization towards the M1 phenotype.

4. Verification of the Lung Penetration and Retention Ability of the Nanostructure

To ensure effective penetration of the nanostructure through the pulmonary epithelial mucosal barrier, the researchers used chitosan (CS) as an excipient to enhance the penetration and retention time of the nanostructure. Fluorescence imaging experiments showed that CS-loaded nanostructures exhibited stronger fluorescence signals in the lungs, indicating that they could effectively penetrate the pulmonary barrier and remain retained for extended periods.

5. In Vivo Verification of Antiviral and Anti-Inflammatory Effects

Finally, the researchers evaluated the antiviral and anti-inflammatory effects of the polyaptamer nanostructure in K18-hACE2 mouse models. The results showed that CS-loaded nanostructures significantly inhibited pseudovirus infection and alleviated pulmonary inflammatory responses. Using bioluminescence imaging, Western blotting, and flow cytometry, the researchers further confirmed the nanostructure’s antiviral effects. Additionally, histological analysis demonstrated that the nanostructure could significantly reduce the infiltration of inflammatory cells in the lungs and the expression of oxidative stress markers.

Conclusion and Significance

This study successfully developed a novel antigen spatial-matching polyaptamer nanostructure that can precisely match the S protein of coronavirus, enhancing the binding ability of aptamers and effectively blocking viral infection. Simultaneously, the loaded anti-inflammatory drug tannic acid can synergistically alleviate pulmonary inflammatory responses. The study also used chitosan to enhance the lung penetration and retention of the nanostructure, further improving its therapeutic effect. This research provides a rapid and effective therapeutic strategy for combating emerging coronavirus infections, possessing significant scientific value and application prospects.

Research Highlights

  1. Antigen Spatial-Matching Strategy: Through precise matching of the coronavirus S protein, the polyaptamer’s binding ability and antiviral effect were significantly enhanced.
  2. Synergistic Antiviral and Anti-Inflammatory Functions: The loaded tannic acid efficiently scavenges free radicals, alleviates pulmonary inflammatory responses, and achieves dual effects of antiviral and anti-inflammatory actions.
  3. Lung Penetration and Retention: Chitosan enhances the lung penetration and retention time of the nanostructure, improving its therapeutic efficacy in the lungs.
  4. Rapid Response to Emerging Viruses: The nanostructure can rapidly respond to infections from different coronaviruses by adjusting the aptamer sequence, linkage distance, and size, possessing broad application potential.

This research provides new ideas for the treatment of coronavirus infections and offers important technological reserves for responding to future public health emergencies.