Cover news reporter: Chen Yanfei

  On August 26, the reporter learned from the official website of the national nanoscience center that scientists have developed a new type of spectral anti coronavirus nanomaterial. This achievement was published in Nature Nanotechnology, an international top journal in the field of nanotechnology, on August 22, with the title of "a nanomaterial targeting the spike protein captures sars-cov-2 variants and promotes virtual elimination".

  It is understood that the nanomaterial has broad-spectrum antiviral activity against novel coronavirus and various mutant strains, and its excellent antiviral efficacy has been proved in cells, human respiratory organs and animals. The research is expected to provide a new strategy for the development of broad-spectrum anti covid-19 drugs, but it still needs a series of clinical trials to become a real drug on the market.

  The research is the result of cooperation between Shenzhen Institute of advanced technology of Chinese Academy of Sciences, national nanoscience center, Institute of high energy physics of Chinese Academy of Sciences and Kunming Institute of zoology of Chinese Academy of Sciences.

  Antiviral effects have been demonstrated in cells, organoids and mice

  Based on the host infection mechanism of novel coronavirus, the research team developed a copper indium phosphorus sulfur two-dimensional nanomaterial (CIPS) that can selectively and efficiently bind to the spike protein of novel coronavirus.

  CIPS can selectively and efficiently bind the spike protein (s protein) of many coronavirus variants, including delta and Omicron, and then block the infection of novel coronavirus to host cells. This study explained the amino acid site of CIPS binding to S protein of novel coronavirus and clarified its antiviral mechanism, and confirmed its anti novel coronavirus effect on cells, organoids and mouse animal models, that is, CIPS can effectively inhibit the host infection of novel coronavirus, effectively alleviate the lung inflammation of mice caused by novel coronavirus infection, and promote the host clearance of the virus. Based on the principle and properties of "nano protein crown", this research designed a new nano material that can capture the spike protein of novel coronavirus efficiently, and provided a new idea and strategy for the development of broad-spectrum anti novel coronavirus drugs.

  Nanomaterials can block effective contact between virus and host cells

  How does novel coronavirus invade the human body? The S protein located on the surface of novel coronavirus is like a "key". After binding with the "door lock" of angiotensin converting enzyme 2 (ACE2) receptor on the cell surface through the receptor binding domain (RBD) of the protein, it can open the door of the cell and make the virus invade the host cell. The "key" of S protein and its RBD domain has become the main target of therapeutic drugs, neutralizing antibodies and vaccines.

  Over time, the mutation of novel coronavirus produced a large number of mutant strains. The common feature of these variant strains is that there are different amino acid mutation sites in the S protein. Take the most popular Omicron strain as an example, its S protein has more than 30 mutation sites, of which the number of mutations in the RBD region is as high as 15. Amino acid site mutations may affect the effects of neutralizing antibodies and vaccines. Recent studies have shown that the potency of various neutralizing antibodies against novel coronavirus against Omicron variant virus strains is significantly reduced.

  Nanomaterials have been widely studied as delivery carriers of vaccines, antibodies or antiviral drugs. However, nanomaterials can also block the effective contact between the virus and the host cell through the interaction with the surface protein of the virus, and inhibit the host infection of novel coronavirus. Therefore, nanomaterials have the potential to become antiviral drugs.

  CIPS can efficiently bind novel coronavirus and four VOC variants

  The researchers screened two-dimensional nanomaterials CIPS with excellent anti novel coronavirus performance from a series of nanomaterials. It can significantly inhibit the infection of virus to host cells at the cellular level, and has low toxicity, high drug safety selectivity index, and excellent drug potential. Using the human respiratory organoid model, the researchers confirmed the antiviral effectiveness of CIPS and confirmed that it can reduce the epithelial damage caused by the infection of novel coronavirus on the respiratory epithelial tissue. Finally, the researchers verified the anti covid-19 effect of CIPS by using the mouse novel coronavirus infection model. When CIPS is used as a preventive and therapeutic drug, it can significantly reduce the infection of novel coronavirus on lung tissue and inhibit the lung inflammation caused by novel coronavirus.

  At present, more than 1000 variants of novel coronavirus have been found, among which alpha, beta, gamma, Delta and Omicron are defined as "variant of concern" by the World Health Organization (who) due to their obvious pathogenicity and wide spread.

   The effectiveness of currently used vaccines and neutralizing antibodies against VOC is still controversial. Several studies have confirmed that some neutralizing antibodies are ineffective against Omicron. The research team found that CIPS can selectively and efficiently bind to the S protein of novel coronavirus and four VOC variants (alpha, beta, Delta and Omicron) and interact with the RBD domain, which can not only change the structure of RBD, but also competitively bind to the binding region of its ACE2 receptor. As a result, the "key" of S protein can not recognize the "door lock" of the host cell receptor, so it can broadly inhibit the invasion of novel coronavirus and variants into the host cell.

  Because the high affinity between CIPS and novel coronavirus is the basis of its antiviral activity, it is necessary to clarify the interface structure of the combination of CIPS and coronavirus. Therefore, the researchers characterized the binding site of CIPS with the RBD domain of S protein of novel coronavirus and mutant strain by using the lysine reactivity analysis and characterization technology and molecular dynamics simulation of Dalian coherent light source biological mass spectrometry experimental station, revealed the molecular mechanism of CIPS antiviral, and laid a theoretical foundation for the subsequent pharmaceutical development of CIPS.

  Experiments on cells, organoids and mouse animal models showed that CIPS combined with novel coronavirus could not only inhibit the infection of virus to host cells, but also promote the clearance of virus by macrophages. Macrophages are effector cells that play an important role in the immune system of the body, and can effectively remove foreign invaders. CIPS, as a foreign substance, can be recognized, captured and degraded by macrophages in the lung. At the same time, as a degradable two-dimensional nanomaterial, CIPS can act as a "glue" or "trap", specifically adhere to the spike protein on the surface of novel coronavirus, capture and attach virus particles to form a virus CIPS complex, cause macrophages to take up, degrade and clear the virus CIPS complex, induce subsequent anti-virus immune response, and improve the anti-virus efficiency.

  CIPS is safe and effective with good biocompatibility

  Good biocompatibility is the premise of safe application of nanomaterials in biomedical field. In order to further evaluate the biological safety of CIPS, based on inductively coupled plasma mass spectrometry (ICP-MS), the researchers studied the physiological process of CIPS absorption, distribution, metabolism and excretion in mice, and combined with synchrotron radiation soft X-ray transmission imaging (nano CT), X-ray fluorescence imaging (XRF), X-ray absorption spectroscopy (XAFS) and other technologies to observe the cellular and tissue uptake, absorption The distribution, degradation, metabolism, excretion and other behaviors showed that CIPS administered by nasal drip could be rapidly metabolized from the lungs of mice within 7 days, and the metabolites could be discharged from the body through urine.

  In addition, CIPS rarely enters the blood and other visceral tissues, and no damage to various tissues and organs has been observed, and no hematotoxicity and systemic immune toxicity have been induced. The above results show that CIPS is a safe and efficient nano material with good biocompatibility and biodegradability.