Genomic Exploration of Origin

Bats as a reservoir

A publicly available data set of sequenced genomes shows that SARS-COVID like viruses are abundant in bats, making them the most likely reservoir for the illness. Bats, however, were likely not hosts that transmitted to humans as the virus in humans shows mutations pointed to an intermediate host.

How many times did the virus jump from animal to human?

The small variation in the genomes sequenced points to a single event. The virus jumped to humans and spread through interaction. This is valuable information for potential vaccine development as multiple strains the population increase difficulty to control. Non-flu zoonotic viruses typically do not transfer host species as they have acclimated to a host type and are generally unfit to populate in other species.

Easily transmittable AND severe

Generally respiratory viruses follow a common troupe. The higher in the respiratory system the more easily transmittable, such as the flu. The lower in the respiratory system the more severe, but less transmittable. COVID-19 exhibits both characteristics making it easily transmittable and severe. This is very odd, begging the following question: how can COVID-19 do that?

HOW?

Above is the sequenced genome of COVID-19. It displays 4 notable things. The first arrow, denoted by 1, points to a single gene called the spike protein. This is the protein that binds onto human cells, allowing it to infect humans. The second arrow, denoted by 2, points within the spike protein to the receptor binding domain (RBD) which specifically binds to the human receptor called ACE2. The RBD shows two noteworthy things: 1) It seems to very capable of binding to the human receptor, but bad at binding to the bat receptor. 2) It is similarly good at binding to the pangolin receptor as human. The third arrow, denoted by 4, shows the insertion of a polybasic cleavage site. Once the virus binds to the cell, via the S1 subunit, it needs to cleave the protein in order to actually infect the cell. COVID-19 shows a specific site dedicated to this process, where SARS did not, making it highly efficient at infecting human cells. This is likely what makes COVID-19 much more transmittable than its brother SARS. Additionally, this polybasic cleavage site is not observed in other SARS-like coronaviruses.

This graphic shows the RBD across the human virus, pangolins, bats, and the SARS we saw in the past. What is worth noticing is that viruses from pangolins have exactly the same sequence as the one infecting humans today. This shows us that the ability to bind very efficiently to human receptors is actually something that developed and was occurring in pangolins. The natural selection and evolution that occurred in pangolins prepared the virus to infect humans. This shows why COVID-19 is different from other zoonotic viruses and presented as a highly efficient virus in human hosts, its limited time in humans notwithstanding.

Furin Cleavage Site

COVID-19 shows a novel furin cleavage site when compared to similar viruses in other species and may be a further explanation for why it is adept at targeting humans. Researches have inserted furin cleavage site into other viruses and have observed expanded host range and ability to infect more diverse cells. Additionally, we have seen avian viruses acquire furin cleavage sites which make them more pathogenic. The furin cleavage site is the most promising explanation of how COVID-19 is able to be both severe and highly transmittable as it is able to bind to more cells along the respiratory track (both high and low). The SARS seen in the past was unable to do this and stayed very low in the lungs.

Contributed by: Rohan KheterpalSource: Kristian Andersen, PhD, Scripps Researchhttps://www.youtube.com/watch?time_continue=3&v=l1OEgl5Bgls&feature=emb_logo

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