Bengaluru: Ever since the novel coronavirus started spreading Covid-19 far and wide, researchers have been scrambling to figure out how this virus was transmitted to humans.
The first known case in a human stemmed from a wet market in Wuhan, China, where not only was fresh meat available for sale, but there was also trade in legal and illegal wild animals. Genetic analysis of the virus, also known as the SARS-CoV-2 due to its similarity to the original Severe Acute Respiratory Syndrome (SARS) virus, has revealed that the virus originated in bats.
But how it came from bats to humans, whether directly or through an intermediate animal, is yet to be determined. And understanding this is key to figuring out how to control the disease and prevent it.
Initial reports suggested that the virus might have come from bats through snakes, but this was quickly replaced by pangolins. Pangolins are endangered, anteater-like mammals that are trafficked illegally in China due to their use in pseudoscientific traditional medicine.
The pangolin theory took hold for a while, but soon, studies came out showing that the similarities between the novel coronavirus and the viruses found in pangolins’ bodies were not enough to be conclusive. And this week, yet another study came out with even more worrying information about pangolin coronaviruses.
What are these researchers working on exactly to determine this intermediate host?
Virus entry mechanism
The virus enters the body by binding to something called the ACE2 receptor. ACE stands for Angiotensin converting enzyme, and ACE2 is an enzyme that is attached to the cell membranes in our lungs, kidneys, heart, intestines, and arteries. ACE2 is capable of lowering blood pressure and plays a protective role in cardiovascular health.
Previous studies have noted that the SARS-CoV-2 seems to be optimised for binding to ACE2 through a ‘spike protein’. This protein helps with the entry in a manner similar to SARS — both viruses have the same protein.
The SARS and SARS-2 viruses share almost 80 per cent of their genetic material.
The new coronavirus has four kinds of structural proteins: The spike (S) protein, the nucleocapsid (N) protein, the membrane (M) protein, and the envelope (E) protein. The S protein helps the virus’s membrane and the cells to fuse together. This offers promise, as therapies to treat Covid-19 could actually use ACE2 antibodies to block the novel coronavirus entry. Such studies are currently being conducted in many parts of the world.
But these four proteins have been found in many viruses, including HIV and others found in bats.
At the point where the S protein enters a cell, there are amino acids present that are essential to the binding process. The residues of these amino acids can be found in infected cells. Scientist have found that when they compared the new virus to the viruses found in a pangolin, there were only five differences in amino acids. For context, when the same coronavirus is studied in humans and in bats, there are 19 differences.
This was the main evidence that pointed to pangolins as the potential intermediate animal.
Study of pangolins
Pangolins are the only known mammals with scales. There are eight species, and they are spread throughout Asia and Africa. They are also the most trafficked mammal in the world, with all eight species under threat from poaching and illegal trade. They are hunted for both food as well as for their scales, which are crushed and used in Chinese medicine. The practice of eating exotic food like pangolins is confined to the upper classes of Chinese society.
It was very likely that pangolins were in the wet market that has since been shut down to prevent the spread of the disease. The shutdown of the market had the one unfortunate effect — that researchers cannot actually trace the pangolin that gave it to a human and find out where it got the virus from.
“Indeed, a number of mammalian species were available for purchase in the Huanan seafood market prior to the outbreak. Unfortunately, because the market was cleared soon after the outbreak began, determining the source virus in the animal population from the market is challenging,” researchers write in a new paper.
The researchers analysed samples collected from 18 Malayan pangolins from August 2017-2018, which were confiscated at customs. These samples were of lungs, intestine and blood. Through genetic sequencing, they were able to detect coronaviruses in five pangolins. They found that coronaviruses in pangolins are over 99 per cent similar to the ones in humans.
The researchers further conducted tests on 12 pangolin samples from another batch dated mid-2018, which tested positive.
They also reviewed other tests conducted before the current outbreak. Five pangolin samples obtained through anti-smuggling operations in March 2019 had coronaviruses that were 72 per cent similar to SARS-CoV-2’s genome. Another study from 2019 also studied pangolin lung samples that are now found to be 86 per cent similar to SARS-CoV-2.
Now, pangolin coronaviruses are said to have between 85.5 per cent and 92.4 per cent similarity to SARS-CoV-2’s genome. These viruses can sometimes recombine and produce new viruses, which contain signatures from the parents.
Analysis of bat coronavirus sequences show gene fragments that are found in various SARS and coronaviruses, including the SARS-CoV-2, and the ones found in pangolins.
But all the pangolin viruses lack a certain furin-like feature (another protein), a key identifying feature of the new coronavirus, which it uses to jump to humans and latch on. It is likely that there was yet another intermediate animal that mutated the virus before it jumped to humans; we don’t yet know. But the similarity to pangolin coronaviruses is a huge health risk for the human population.
The authors don’t conclude that the virus causing the Covid-19 pandemic came from pangolins, but they say that since pangolins carry such similar viruses, they are at a risk of transmitting even more viruses to humans.
“The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of novel coronaviruses and should be removed from wet markets to prevent zoonotic transmission,” they write.
While we wait to find out details about where the virus came from, it is for now, safe to conclude that pangolins were probably involved at some stage of the transfer, and also that pangolins definitely carry viruses that could have the potential to infect us, and should be left a safe distance away from humans.