Phylogenetic studies show how the novel coronavirus enter our body

New phylogenetic studies on the novel (new) coronavirus have revealed a breakthrough. It shows how the agent gains entry into our bodies which may help us formulate treatment protocols.

The novel coronavirus, denoted as 2019-nCoV, is the culprit behind the outbreak of Wuhan pneumonia. Currently, 1,330 people are suffering due to this agent in China alone, and the current death tolls rise to 41. In addition to this, there also 24 confirmed cases outside China, according to Caixin. Since the outbreak is on the roll, scientists are working tirelessly to understand how the novel agent works. Several studies are being conducted to understand the phylogenetic evolution of the agent. Recently, two independent works from China and the U.S. might give an idea of how this novel agent works. It is said that the agent might use Angiotensin-Converting Enzyme 2 (ACE-2) as a mediator for the cell entry thereby affecting the individual. The mechanism is similar to that of SARS-CoV which lead to a similar outbreak back in 2002.

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The study

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Scientists have been closely monitoring coronaviruses for the past 17 years since the SARS outbreak. The coronavirus group includes many viruses with animal reservoirs. But 229E, NL63, OC43, HKU1, MERS-CoV and SARS-CoV as six members were previously affecting humans until the 2019-nCoV came in as the seventh member. It is also seen that most of the members in the clade are isolated from bats especially Horshoe bats (Rhinolophus spp). Therefore, scientists decided to isolate the novel agent in the evolution tree.

The initial sequencing of the novel agent gave us an insight that it belongs to Betacoronavirus which contains both SARS-CoV and MERS-CoV. Further reverse genomic sequencing told us that the virus more closely resembles SARS-CoV than that of MERS-CoV. The two recent genomic sequences indicate three mutations at similar places which with a recent common ancestor. As of now, 18 genomes of the novel agent are isolated.

The mechanism

Cell entry is an essential mechanism by which virus gains entry into their host. Especially, zoonotic viruses rely on this mechanism to take control of the host effectively. The cell entry is coded via surface glycoproteins which will bind to the host cell. In the case of the Betacoronaviruses, the Receptor Binding Domain (RBD) facilitates cleaving proteases on the cell thereby enters the cell. Known receptors of Betacoronaviruses include ACE-2 (Angiotensisn Converting Enzyme-2) for SARS-CoV and Dipeptidyl peptidase for MERS-CoV (Middle Eastern Respiratory Syndrome).

Due to similarities with SARS-CoV, it is seen that the novel agent also adopts a similar mechanism to it. Scientists are almost sure that the novel agent uses ACE-2 as a binding agent to enter the cell. But additionally, scientists also encountered a different clade that had an additional receptor-mediated entry which is yet to be explored.

With these studies on the roll, different organizations like NIH, VIDO-InterVAc are already trying to find effective vaccines against the agent.

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Source: biorxiv

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