{% extends "layout.html" %} {% block title %}Description{% endblock %} {% block lead %}Describe all the safety issues of your project.{% endblock %} {% block page_content %}

DESCRIPTION

Background

The SARS-CoV-2 has been wreaking havoc for three years,which has made humanity lost too much. Many people have lost their jobs, some have developed depressive symptoms because of it, and some children have lost their sheltered families, even some elderly people have died from being neglect or starvation in their homes. [1]

A white flag 2021 with words to honor loved ones is seen on a lawn near the Washington Monument in Washington, DC, Sept. 17,2021. Photo by Xinhua News Agency reporter Jie Liu

Just when we thought the fog of the epidemic was finally lifting, the SARS-CoV-2 was always able to mutate new variants that would elude the human immune system. To date, there have been hundreds of variants of the SARS-CoV-2. [2]

Haplotype network analysis using genome-wide single-nucleotide variations of VOC Gamma in the world. The VOC Gamma were compared with GISAID-available SARS-CoV-2 genomes (n = 1502, updated on October 09, 2021). (A) The Pango lineages of VOC Gamma. The lineages are marked with different colors. (B) The countries distribution of VOC Gamma. The colors represent different countries. Scale lengths represent the genetic distance.

They had better disguising which can help them escape the immune response, or even reduce the effect of the vaccine. [3] The epidemic is still spreading around the world because humans can not develop a vaccine as quickly as they can.

Now, although people are returning to normal life, the bigger bad news is that wildlife habitat is being destroyed by climate change. This allows many wildlife habitats to overlap with anthropic zone, which increases the chances of zoonosis. Perhaps in the future, we need to deal with more complex infectious diseases, things will be more complicated then. [4] So are really ready for the next one? What exactly should we learn from this outbreak?

Here, the FAFU's answer is that we should identify and intervene epidemic in some areas as early as possible.

Inspiration

Wastewater epidemiology

Through the detection of pathogens in wastewater, people can predict the potential outbreak of epidemic diseases in cities. In Japan and Israel, poliovirus, hepatitis virus and SARS-CoV-2 were detected in wastewater, and the further spread was prevented early in the outbreak.

Studies have shown that the SARS-CoV-2 can also infect small intestinal epithelial cells [5] , causing diarrhea in infected people. These viruses are released into the city's wastewater system along with domestic wastewater.

At present, wastewater epidemiology is also used in the local epidemic warning and dynamic monitoring. In the Netherlands and Spain, viral RNA was detected in wastewater more than a dozen days before patient zero was diagnosed. [6]In a French experiment, researchers performed four relatively uniform tests in Paris, and the results showed a good linear correlation with local actual crowns prevalence trends. [7] This proves that we can use the relevant markers in wastewater to predict the trend of local outbreaks.

However, the current wastewater epidemiological testing needs to rely on manual sampling and testing. A great deal of manpower and material resources were expended. Therefore, we want to develop a device that can sample, detect and report on its own, which can reduce the burden of epidemic prevention and control.

ACE2 and spike

In combination with the theory of wastewater epidemiology and the background of the current SARS-CoV-2 pandemic, we hope to find a protein that can bind to the SARS-CoV-2 and act as an anchor protein on the wastewater epidemiology device, so that it can catch the new SARS-CoV-2 in the wastewater. After reviewing a large number of literature, we determined that ACE2 and the s 1 subunit of the RBD domain of SARS-CoV-2 have binding ability in human body, but the flow rate of wastewater is too fast to detect the presence of the SARS-CoV-2 in a short exposure time. As for this question, we wanted to modify the existing ACE2 protein so that it could bind better to the SARS-CoV-2. By reading the literature, we found that N82 on the ACE2 protein is in closer contact with F486 on the sars-cov-2s protein than M82 on ACE2[8]. Therefore, we wondered whether the point mutation could be used to enhance the original ACE2 protein so that it could strongly bind to the S1 protein subunit of SARS-CoV-2 .

Random library

As there are many substances in wastewater, we cannot say that the binding to ACE2 is SARS-CoV-2, that is, the S1 protein subunit. Therefore, we hope to find more proteins that can strongly bind to the S1 protein subunit of SARS-CoV-2 for further verification. Based on this idea, we want to construct a short random peptide library [9] , then we screened the S1 protein subunits of the SARS-CoV-2 to find the peptides that could bind to the S1 protein.

Enrichment of Virus

Before we start testing, the first thing we need to do to is to enrich the virus without changing the structure of the virus coat. We came up with the idea of making the virus "stick" to E. coli by anchoring spike-binding peptides on its surface. At the same time, we hope to use light to promote the directed movement of E. coli. We designed two circuits in which E. coli move at high speed in the blue light region and split and die over a period of time, while stagnating in the lightless region.

Detection of Viruses

After obtaining the gripper, we used the PmrAB two-component system as our detection element, which would trigger the sensing mechanism and emit the corresponding intensity of fluorescence when the virus was outside.

Reference

[1] Liu Suihan, Du Yukai, Gan Yong, Peng Songxu. Factors influencing social support in Chinese population under the background of COVID-19 [J]. Chin J Sociomedin, 222,39(04):408-411.

[2] Zhang Q, Guo HL, Wang J, Zhang Y, Deng PJ, Li FF. Structural Genomic Analysis of SARS-CoV-2 and Other Coronaviruses. Front Genet. 2022 Apr 8;13:801902. doi: 10.3389/fgene.2022.801902. PMID: 35464844; PMCID: PMC9024071.

[3] Mora C, McKenzie T, Gaw IM, Dean JM, von Hammerstein H, Knudson TA, Setter RO, Smith CZ, Webster KM, Patz JA, Franklin EC. Over half of known human pathogenic diseases can be aggravated by climate change. Nat Clim Chang. 2022 Aug 8:1-7. doi: 10.1038/s41558-022-01426-1. Epub ahead of print. PMID: 35968032; PMCID: PMC9362357.

[4] Gao QY, Chen YX, Fang JY. 2019 Novel coronavirus infection and gastrointestinal tract. J Dig Dis. 2020 Mar;21(3):125-126. doi: 10.1111/1751-2980.12851. Epub 2020 Mar 10. PMID: 32096611; PMCID: PMC7162053.

[5] MEDEMA G,HEIJNENL,ELSINGAG,etal. Presence of SARS-Coronavirus-2 RNA in sewage and correlation with reported COVID-19 prevalence in the early stage of the epidemic in the Netherlands[J]. Environmental Science & Technology Letter,2020,7 (7) : 511-516.

[6] WURTZERS,MARECHALV,MOUCHELJM,etal. Time course quantitative detection of SARS-CoV-2 in Parisian wastewater correlates with COVID-19 confirmed cases [J]. medRxiv,2020. DOI: 10. 1101 /2020. 04. 12. 20062679.

[7] Gangadevi S, Badavath VN, Thakur A, Yin N, De Jonghe S, Acevedo O, Jochmans D, Leyssen P, Wang K, Neyts J, Yujie T, Blum G. Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19. J Phys Chem Lett. 2021 Feb 25;12(7):1793-1802. doi: 10.1021/acs.jpclett.0c03119. Epub 2021 Feb 12. PMID: 33577324; PMCID: PMC7901140.

[8] Luan J, Lu Y, Jin X, Zhang L. Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection. Biochem Biophys Res Commun. 2020 May 21;526(1):165-169. doi: 10.1016/j.bbrc.2020.03.047. Epub 2020 Mar 19. PMID: 32201080; PMCID: PMC7102515.

[9] Yang M, Wu Z, Fields S. Protein-peptide interactions analyzed with the yeast two-hybrid system. Nucleic Acids Res. 1995 Apr 11;23(7):1152-6. doi: 10.1093/nar/23.7.1152. PMID: 7739893; PMCID: PMC306824.

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