The Genome and Proteins involved in COVID-19
In this series of posts, we will talk about the biological side of COVID-19, as understood by a high school student. Click here to view previous articles.
What does the genome code for?
As the disease emerged, scientists rushed to identify the genomic sequence of SARS-CoV-2, the virus that causes COVID-19. Enclosed by the nucleocapsid, the ~29,903 RNA nucleotides form the virus’s genetic code. While this number is minuscule compared to the 3 billion nucleotides carried by humans, SARS-CoV-2’s single-stranded RNA coronavirus genome is longer than that of any other RNA virus — three times longer than HIV’s 9,749 nucleotides and twice as long as the influenza A virus’s 13,588 nucleotides. The 29 proteins that the SARS-CoV-2 genome codes for, have been enough to hijack enough cells in the body to take the lives of over 100,000 people. In order to develop a form of treatment for this disease, we must understand the SARS-CoV-2 genome, and the 29 proteins it produces.
The Replicase Gene
The first ~21 kilobases of the genome code for the replicase gene. As we explained in the previous post, this gene codes for the mechanism that coronaviruses use to replicate their genome inside the host. Initially, this gene produces two polyproteins. Approximately 13 kilobases code for the first polyprotein, and 8 kilobases code for the second polyprotein. These polyproteins eventually break themselves down into ~16 small non-structural proteins (NSP), which are proteins that are not part of the viral particle. While the function of some of these proteins remains a mystery, scientists have a good understanding of a few. Some scientists believe that some proteins might have no function at all. The first protein, NSP1, is responsible for reducing the production of the host cell’s proteins, allowing the cell to produce more viral proteins. As a result, this also reduces the production of antiviral proteins. Another protein, NSP3, cuts loose other viral proteins, allowing them to do their specific task. NSP3 can also block the host cell’s attempt to fight the virus. These are among the few non-structural proteins that are currently being examined the most.
Structural and Accessory Proteins
The final third of the genome codes for the four structural proteins — envelope, membrane, spike, and nucleocapsid proteins — and additional accessory proteins that counteract the defensive response by the host cell. These accessory proteins are the least understood and many scientists are focusing on gaining a better understanding of how they contribute to the spread of the disease. One of these proteins is ORF3a, which allows newly produced viruses to escape by making holes in the cell membrane. ORF3a is responsible for inflammation, arguably the most serious symptom of the COVID-19. Another accessory protein, ORF 6, blocks signals between infected cells and the immune system.
What does this mean?
By researching the function of these proteins, scientists have already learned a lot, but there is yet a lot more left to understand. Scientists are confident that a better understanding of these proteins could potentially lead to the discovery of a treatment procedure, or possibly a cure, for COVID-19. The aim is to find a weak spot in the genome and proteins to exploit. The first approach being considered is applying a drug that would bind to and inhibit the function of one of the proteins. Scientists are hoping that targeting one protein will break down the entire system that the virus uses to spread. Other researchers are focusing on the interaction of the proteins with the host cell and creating a drug that would target the host instead of the virus. This approach would aim to prevent the host cell from being “tricked” by the viral proteins to replicate the virus. At the moment, the emphasis is on testing if existing drugs would be effective against parts of SARS-CoV-2. By comparing the viral proteins to those of other diseases such as SARS-CoV and MERS-CoV, it might be possible to identify an existing drug, originally meant for other diseases, that might also be effective against SARS-CoV-2.
With significant advancements being made by researchers every day, scientists are certain to make the ground-breaking discovery any time soon. In the next post, we will take a look at how scientists have handled previous coronavirus outbreaks the human population has encountered.
References
COVID-19: Genetic network analysis provides ‘snapshot’ of pandemic origins. (2020, April 09). Retrieved from https://www.sciencedaily.com/releases/2020/04/200409085644.htm
Corum, J., & Zimmer, C. (2020, April 03). Bad News Wrapped in Protein: Inside the Coronavirus Genome. Retrieved from https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html
Mousavizadeh, L., & Ghasemi, S. (2020, March 31). Genotype and phenotype of COVID-19: Their roles in pathogenesis. Retrieved from https://www.sciencedirect.com/science/article/pii/S1684118220300827
Severe acute respiratory syndrome coronavirus 2. (2020, April 09). Retrieved from https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2
Tohya, Y., Narayanan, K., Kamitani, W., Huang, C., Lokugamage, K., & Makino, S. (2009, May 15). Suppression of Host Gene Expression by nsp1 Proteins of Group 2 Bat Coronaviruses. Retrieved from https://jvi.asm.org/content/83/10/5282
Understanding SARS-CoV-2 and the drugs that might lessen its power. (n.d.). Retrieved from https://www.economist.com/briefing/2020/03/12/understanding-sars-cov-2-and-the-drugs-that-might-lessen-its-power
Zhang, S. (2020, April 08). The Best Hopes for a Coronavirus Drug. Retrieved from https://www.theatlantic.com/science/archive/2020/04/what-coronavirus-drug-will-look-like/609661/
