动物模型,新冠状病毒 z-bo 2020-10-13 785

　　The epidemic of the new coronavirus has spread worldwide, and the epidemic situation in many places is still very serious. So far, there are no effective new coronavirus (SARS-CoV-2) specific drugs and vaccines. In order to speed up the development of vaccines and antiviral drugs, we need an economical, easy-to-operate and easy-to-obtain animal model.

　　In addition to choosing red lizard monkeys and genetically modified mice for COVID-19, is there a more economical and effective treasure model for pre-clinical research animal models? View

　　Ature, Virus, ClinInfectDis and the latest research in Anti-Virus magazines.

　　1. There is an urgent need for an easy-to-operate small animal model

　　In previous animal experiments on SARS-CoV, SARS-CoV interacted with the host's angiotensin converting enzyme 2 (ACE2) receptor through its surface spike protein. display. Causes the infection mechanism. Recent studies have shown that SARS-CoV-2 also opens the door to human infection by binding to the ACE2 receptor in human lung cells. However, the binding of SARS-CoV-2 to the mouse ACE2 receptor is restricted, and the procedure is restricted. Application of mouse in COVID-19 research.

　　COVID-19 studies 2, 3 and 4 have reported transgenic hACE2 mouse models and red-throated monkey models, but the availability of these models is limited. In the case of hACE2 transgenic mice, the expression of human ACE2 in the transgenic mice is not consistent. Pneumonia and moderate weight loss occurred after SARS-CoV-2 infection, but there were no obvious histological changes in non-respiratory tissues. Although it is reported that hACE2 transgenic mice support SARS-CoV replication in airway epithelial cells, they may be related to neurological death caused by high expression of ACE2 in the brain. Moreover, such transgenic mice are expensive, and it is difficult to obtain a large number of animals suitable for research. Red lizards are not only very expensive, but also a very scarce resource at present, and most research units have expertise in handling non-human primates, biosafety level 3, and lack of equipment.

　　2. Research shows that hamsters are an ideal model for COVID-19 research

　　Previous studies have shown that golden hamsters can support SARS-CoV replication, but Middle East Respiratory Syndrome has proven unable to support coronavirus (MERS-CoV) replication. , MERS-CoV virus uses dipeptidyl peptidase 4 (DPP4) protein as the main receptor for virus invasion. 5. Further studies have shown that different SARS-CoV strains have different toxicity to golden hamsters. For example, after SARS-CoV-Frk-1 strain infects hamsters, it is lethal. After infection with the SA S-CoV-Urbani strain, virus replication in hamsters can be detected, but it is usually not detected in animals. Show obvious abnormality 6.

　　Question: How did hamsters get infected with the SARS-CoV-2 strain that occurred at the end of 2019?

　　"Studies show that the SARS-CoV-2 strain induces infection through the human hACE2 receptor. How does the structure of the ACE2 receptor in hamsters and other animal models differ from the human ACE2 receptor? This is a problem that scientists are actively studying.

　　ACE2 receptor: Comparison between different animal models and humans

　　The 29 amino acid residue sequence of the

　　JasperFuk-WooChan mammalian species was first compared between humans and others, and the results showed that in the interface region, the red-spotted monkey ACE2 is 100% identical to human ACE2. The ACE2 protein of Syrian hamster and common marmoset is also very similar to human ACE2, with only three. 4 mutations. Further structural analysis was performed to predict the interaction between the 29 amino acid residues on the ACE2 interface and the SARS-CoV-2 surface-added glycoprotein RBD (see the figure below). The results show that SARS-CoV-2BD not only binds well to human and red-tailed monkey ACE2, but also binds well to Syrian hamster ACE2 7. The interaction between SARS-CoV-2 spike protein and hamster ACE2 may be more effective than mouse ACE2.

　　Jimu: The infectious properties of the new coronavirus are similar to humans

　　Based on the above results, ImaiM et al. further evaluated the replication ability and etiology of the SARS-CoV-2 isolate in Syrian hamsters. The results of the study show that the SARS-CoV-2 isolate can effectively replicate in the lungs of Syrian hamsters and these animals, and has common imaging features of patients with COVID-19 pneumonia. Caused serious pathological changes in the lungs. Hamsters infected with SARS-CoV-2 can induce the production of neutralizing antibodies and protect them from reinfection8. In addition, passive transfer of convalescent serum to naive hamsters can inhibit virus replication in the lungs. Similarly, SinFunSia's findings also indicate that the characteristics associated with SARS-CoV-2 infection in golden hamsters are similar to mild SARS-CoV-2 infections found in humans. Research results: All the above findings indicate that hamsters are very sensitive to SARS-CoV-2 infection, do not require prior adaptation, and can produce severe pneumonia similar to COVID-19. I'm. Importantly, compared with ferrets and non-human primates, the use of this animal model helps to quickly evaluate vaccine or antiviral therapy candidates at a relatively low cost. In addition, most hamsters did not die from SARS-CoV-2 infection. This is consistent with human infection. The Syrian Golden Hamster is a useful small animal model that can be used to evaluate vaccines, immunotherapy and antiviral drugs.