The Biology of SARS-CoV-2: Understanding COVID-19 Transmission

The Biology of SARS-CoV-2: Understanding COVID-19 Transmission

COVID-19 is spread from person to person in several different ways including coughing, sneezing, breathing, and through saliva. This virus is spread through these methods since there are respiratory droplets, or droplets of saliva or mucus. People that are in close contact with one another are often the ones who spread the virus to each other. People who also in direct contact with one another also often spread the virus to each other. There may also be some instances when the virus may spread within crowds of people who are indoors since there is poor air ventilation and these respiratory droplets can be spread through a number of people. When these droplets are spread from an infected person to a non-infected person, the virus will enter the system of the non-infected individual and manifest into the common COVID-19 symptoms.

During SARS-CoV-2 replication, the spike protein is cut twice in order to facilitate infection of the host cell: once using furin and another time using TMPRSS2 (Scudellari 2021). Explain how the two cuts work and why they are important for infection. During replication of the COVID-19 virus, there are two cuts of the spike protein that contribute to infection. One of the cuts is done through TMPRSS2, which is an enzyme that is located outside of respiratory cells. This enzyme cuts the spike protein and allows for the hydrophobic amino acids to attach to the host cell membrane. This member then uses with the viral membrane and results in the virus having a quicker entry into the host cell. Another cut is done using furin. Furin is thought to cause a cut during the assembly of the viron or possibly before it is released. This cut also helps the virus enter the cell quicker. Without these cuts, the virus would take longer to enter the host cell. Evolution: There is an ongoing debate about the origin of the SARS-CoV-2 virus. How can scientists use genome sequencing and phylogeny to determine where the virus might have originated?

Genome sequencing is used to match up certain samples to viruses. From a sequence, scientists could try to determine where the virus may have originated from. The genome of the COVID-19 virus in humans and in other species was compared and it showed that they were not relevant hosts of the virus. This specific species, pangolins, was not connected to where the origin of virus has been thought to come from. With genome sequencing, scientists were able to discover that the COVID-19 in humans genome was very similar to those in bats located around China.

Review this article and this article to learn why the SARS-CoV-2 delta variant is more dangerous than the original SARS-CoV-2 variant.  Describe how mutations in the receptor binding domain (RBD) and the furin cleavage site impact transmission of the delta variant: Receptor Binding Domain: The RBD binds to ACE2, which is expressed on type 2 pneumocytes in the lung. The binding affinity of the RBD for ACE2 is much higher than that of the spike protein for its cognate receptor, angiotensin-converting enzyme 2. This results in a high viral load in the lungs and an increased risk of severe disease. Therefore, the RBD is considered the most important determinant of pathogenicity. Mutations in the RBD can alter the structure or function of the virus and affect the ability of the virus to bind to the host cell surface receptor. For example, a mutation at residue 627 from threonine to alanine has been identified as a major cause of the outbreak in Wuhan, China. Although it does not change the amino acid sequence of the RBD, it changes the conformation of the loop region that contains residues 623–629. It also affects the interaction between the RBD and ACE2 by changing the orientation of the loop region relative to the rest of the molecule.  Furin Cleavage Site: The furin cleavage site is located within the S1/S2 subunit of the S protein. Furin is a protease that processes precursor proteins into their mature forms. In coronaviruses, furin cleaves off the N-terminal fusion peptide during maturation of the spike glycoprotein. Mutation of the furin cleavage site prevents processing of the spike protein and causes accumulation of uncleaved precursors. These precursors are then incorporated into virions and may be responsible for enhanced infectivity of the virus. As such, the furin cleavage site is thought to play a role in enhancing the transmissibility of the virus.  The mutation rate of SARS-CoV-2 is quite low compared to other RNA viruses. However, scientists have found more than 12,000 mutations in the SARS-CoV-2 genome. A) Explain why the mutation rate is relatively low. B) Given this information, why have we already identified so many mutations? A: The reason why the mutation rate of SARS-CoV-2 is relatively low is that it has a very high replication fidelity and error correction ability. This means that there are fewer mutations during its reproduction process. In addition, the virus uses a proofreading mechanism to correct mistakes made by polymerase. Since the proofreading function is highly accurate, even if one mistake occurs, it will be corrected within a few bases. This makes it difficult for the virus to mutate into an entirely new form. B: Although the mutations in SARS-CoV-2 is relatively, we have identified numerous mutations, because the virus was isolated from different patients at different times. These mutations were not all created at once, but rather over...