Since, the CoVID-19 infection began scientists are on a race to find its origins. This epidemic caused by a virus called “SARS CoV-2” or “2019-nCoV”. I plan to explain the latest review literature published by Nature that recently highlighted the various causes how this virus came about.

A virus is an organism (a living thing ?) that needs a host in order to replicate and survive. Therefore it infects various kind of cells right from a single-celled bacteria all the way to a complex-being like us. Although there are different species, the underlying mechanism of interaction is all the more same.The infection cycle starts by virus attaching itself using its spike protein (receptor binding region) to a specific receptor of host cell. This specificity determines the range of hosts the virus infects. Then based on the viral species it either enters the cell (coronavirus) or it inserts the genetic material (bacteriophage). Then the viral membrane covering the viral genetic material degrades leading to the replication of the virus. Once, the viral proteins are produced they are assembled into full-fledged viruses, they burst out of the cell and continue infecting other cells.

Fig. left – Bacteriophage ; Fig. Right – Coronavirus Source(Britannica & wikimedia)

2019-nCoV is the virus that’s responsible for CoVID-19 pandemic. Especially, on comparing the various structural and genomic features with other well-documented corona-viruses. They found two distinct features :-

The 2019-nCoV is optimized for binding to the ACE2 human cell receptor- This means the virus is able to infect the human cells more easily due to the fact that its spike protein has effectively mutated to bind near-perfectly with the ACE2 receptor. ACE2 is a receptor present in most major human tissues like lungs, arteries, heart, kidney, and intestines. This is a major factor needed for it’s capability to infect us. The presence of a poly-basic furin cleavage site and O-linked glycans in the spike protein- Normally, a spike protein in a virus is inactive. So, it often needs an host-cell enzyme like furin to convert it to active form to bind properly with the cell surface receptor. Although, there is no clear study on it’s relevance on 2019-nCoV’s transmissibility; a previous study in avian influenza virus has showed that a poly-basic cleavage site was mainly responsible for it’s high pathogenicity. Also, the presence of distinct O-linked glycans could have a relevance in blocking of host immune action in other viruses.

With these differences in mind, one might say that this virus could’ve been artificially modified in labs as a bio-weapon. But there enough substantial evidence to emphasize that these mutations are natural and not man-made :-

The receptor binding region that is present naturally in the 2019-nCoV is far more efficient in recognizing the receptor than the solution that was found through currently-used computational receptor prediction models. In order to design a custom-made lab-grown virus one has to use previously used reverse-genetic system backbone for corona virus to modify to required feature.This was absent through genome comparison studies with 2019-nCoV.

Fig.2 a. Metagenomics analysis of next-generation sequencing b, Genomic organization of 2019-nCoV c, Similarity plot based on the full-length genome sequence of 2019-nCoV vs SARS-CoV and other bat corona viruses. d, Phylogenetic tree based on nucleotide sequences of complete viral sequences (Source :- Peng Zhou et.al 2020)

Therefore, these points clearly point in the direction of “natural selection” as a reason for these mutations. On comparing the genomes with other viruses, it was found out that about 96% 2019-nCoV genome match with a bat coronavirus called RaTG13 (Fig.2c graph indicating nucleotide identity of 2019-nCoV vs other viruses). But, the key difference was that the receptor binding domain did not match with RaTG13. The 2019-nCoV receptor binding domain was highly similar to corona viruses that are present in pangolins, a wild animal that is illegally traded in wildlife markets in China. Therefore, this clearly indicates that the viral spike protein was optimized to bind with human ACE2 cell receptor through natural selection.

a.Nucleotide/protein map indicating the similarity of receptor binding protein with pangolin coronavirus.

b. This indicates the unique poly-basic linkage site present in 2019-nCov and not in other viruses. (Source :- Kristian G. Andersan et.al 2020)

But the poly-basic linkage site unique to 2019-nCoV as it is not present in both of the above-mentioned zoonotic viruses. Although we do not know the importance of this feature, this mutation could have occurred during unrecognized human-human transmission well before the epidemic happened. Hence, there is more study required on both the relevance and origin of poly-basic linkage site in 2019-nCoV virus.

Finally, there are theories claiming that this virus might have escaped a virology labs. But this is clearly misleading because :-

In order to gain a poly-basic linkage site, a virus has to be grown with other highly genetically similar viruses. There is no legitimate study to back this claim. The gaining of O-linked glycans mutation cannot occur in-vitro as it needs host-immune selection action.

In conclusion, it is reasonable to have speculations to the origin of 2019 – nCoV virus but a detailed scientific study is required in order completely understand the pathogen to avoid future outbreaks and fake news. In future, there is more study needed to understand and predict the occurrence of these mutations. Added to this, there is a immediate need for stricter wildlife laws in all countries as it is both beneficial for mankind and animals.