Team:NYMU-Taipei/Description

Description

Background - COVID-19

Prevalence

Coronavirus disease 2019, also known as COVID-19, is an infectious disease caused by the virus, SARS-CoV-2. The disease was first identified in 2019 at Wuhan, Hubei, China, and has since spread throughout the world via the tightly connected global economy. By the end of 2019, all continents have confirmed cases of the disease, except for Antarctica. As the number of cases rise exponentially in many countries due to the strong infectivity of the virus, WHO declared COVID-19 as a global pandemic on March 11th, 2020.

As of September 20th, 2020, the number of total global cases has exceeded 30 million, and the number of global deaths passing 900,000. The top three countries with the highest number of cases include the United States, India, and Brazil. Moreover, due to the limitations of testing capabilities and testing amounts, the true toll of the pandemic is predicted to be ten times larger than what is reported. The prevalence of this particular virus has been unexpected, striking a deep blow to the global society on both economic and social terms. The pandemic has caused the largest economic recession in history. Therefore, it is everyone’s responsibility to try their best to mitigate the losses of the global community.

Transmission

The prevalence of COVID-19 as we mentioned above is mainly due in part to its transmission mechanics. However, COVID-19 is a novel disease and many of its transmission mechanics still deserves more understanding. The major route of transmission of the virus is through close interactions between person-to-person. The main source of infection is through airborne measures, such as respiratory droplets and aerosols, the former is more infectious but drops to the ground more easily, while the latter is less infectious but stays longer in indoor settings. Infections through fecal-oral routes or contaminated surfaces are also possible but less common.

Virus released in the respiratory secretions can easily infect another person if it makes direct or indirect contact with human mucous membranes, which exists in the eyes, nose, mouth of a person.

Pathogenesis

COVID-19 mainly affects the respiratory system, including the upper respiratory tract (sinuses, nose, and throat) and the lower respiratory tract (windpipe and lungs). SARS-CoV-2 accesses human cells via the enzyme angiotensin-converting enzyme 2 (hACE2), which is most prevalent in type II alveolar cells of the lungs. Coronoviruses consist of four structural proteins; Spike (S), membrane (M), envelope (E),and nucleocapsid (N), of which Spike is the main focus of our project studies. Spike is composed of a transmembrane trimetric glycoprotein protruding from the viral surface, which determines the diversity of coronaviruses and host tropism. Spike consists of two functional subunits. S1 subunit is responsible for binding to the host receptor, while S2 is involved in the fusion of the viral and cellular membranes. As for the SARS-CoV-2, its spike protein exhibits significantly stronger binding affinity to the ACE2 receptor than other coronaviruses, shedding light on the high infection and transmission rates of the current pandemic. Our project will try to exploit this property of the virus.

Our Solution

Undoubtedly, researchers around the world are striving to find measures to mitigate the dire consequences of COVID-19. Most of them focus on either developing antibodies that can deactivate the SARS-CoV-2 virus or vaccines that can trigger the immune response of the human body. NYMU-Taipei tries to tackle the problem in a much more elementary approach. By utilizing the nature of strong binding interactions between hACE2 and the spike of SARS-CoV-2, we believe that we would be able to reap the benefits of viral evolution and come up with a more affordable solution.

Off the Crown wants to capture and even destroy virus particles that may come in close contact with individuals. Our goal is to implement our design on surgical masks, contact lenses, and even filtration devices so as to reduce the amount of viruses that would come in contact with human bodies and, thus, reduce the possibility of infection. In order to achieve our goals, iGEM NYMU 2020 engineered a protein construct that includes the hACE2 receptor binding domain, a linker, and a protease that is specific at cleaving spike proteins. The protein construct functions as a capture device and can be implemented on many occasions as a mean to capture, destroy, and even quantify the amount of virus particles on a particular surface. We also consulted for some advice on material science and developed a special gel that has our protein construct attached to its surface, which could readily function as a capture device. Our main goal is to make a modular device that can be built upon or used for many other purposes according to different environmental conditions and implmentation goals.

Inspiration

Inspired by how Taiwan significantly reduced the number of COVID-19 infections by strictly imposing social distancing rules and requiring people to wear surgical masks. We figured that other than developing cures such as antibodies or other medications for people that are infected, preventive measures such as vaccines inside human bodies and capture devices outside human bodies are equally important in the battle against COVID-19.

Just like the saying goes, “an ounce of prevention is worth a pound of cure”. If we can successfully cut down on the exposure of humans to the virus, the infection rate could be significantly reduced and many social distancing regulations and city lockdowns can be relaxed so as to revive the already dwindling economy. Moreover, viruses have to infect host organisms in order to continue their reproduction. If we can reduce the number of infections to a low enough level, it is very likely that the virus will slow down its mutating process and even disappear by itself as it fails to find the next host. Last but not least, we hope to impact the world with our novel idea and commit our efforts to the global fight against COVID-19.

References
  1. Coronavirus disease 2019 (COVID-19): Epidemiology, virology, and prevention; Retrieved from https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-vepidemiology-virology-and-prevention
  2. Coronavirus Disease 2019 (COVID-19); Retrieved from https://emedicine.medscape.com/article/2500114-overview#a1
  3. Coronavirus Disease (COVID-19); Retrieved from https://www.physio-pedia.com/Coronavirus_Disease_(COVID-19)
  4. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU); Retrieved from https://coronavirus.jhu.edu/map.html
  5. 10 Reasons to Doubt the Covid-19 Data; Retrieved from https://www.bloomberg.com/opinion/articles/2020-04-13/ten-reasons-to-doubt-the-covid-19-data
  6. COVID-19 to Plunge Global Economy into Worst Recession since World War II; Retrieved from https://www.worldbank.org/en/news/press-release/2020/06/08/covid-19-to-plunge-global-economy-into-worst-recession-since-world-war-ii
  7. SARS-CoV-2 Transmission; Retrieved from https://www.worldometers.info/coronavirus/transmission/
  8. How Does Coronavirus Spread?; Retrieved from https://www.webmd.com/lung/coronavirus-transmission-overview#1
  9. Cheng-wei Lu, Xiu-fen Liu, Zhi-fang Jia (2020) 2019-nCoV transmission through the ocular surface must not be ignored. doi: https://doi.org/10.1016/S0140-6736(20)30313-5
  10. I Hamming, W Timens, MLC Bulthuis, AT Lely, GJ Navis, and H van Goor (2004) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. doi: 10.1002/path.1570
  11. Koichi Yuki, Miho Fujiogi, and Sophia Koutsogiannaki (2020) COVID-19 pathophysiology: A review. doi: 10.1016/j.clim.2020.108427
  12. Tai, W., He, L., Zhang, X. et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol 17, 613–620 (2020). https://doi.org/10.1038/s41423-020-0400-4
  13. Wikipedia Coronavirus Disease 2019; Retrieved from https://en.wikipedia.org/wiki/Coronavirus_disease_2019

A Project conducted by the 2020 NYMU iGem Team
nymuigem2020@gmail.com
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NYMU iGEM Team @igemnymutaipei
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