Monday, July 5, 2021

Mutation and Strain Biology of Covid-19 Virus

Spanish flue of 1918 
World is still fighting with the third wave of Covid-19 pandemic. Humans do have short memories as we forgot Spanish flu pandemic; a 100 year ago with fatalities in tens of millions at that time. Mutation in influenza, the RNA virus was behind the infamous pandemic. Understanding how virus mutates is critical for making decisions about the vaccines. RNA viruses mutate relatively quickly because they lack a proofreading mechanism to look for and repair errors during replication.

Actually there was no learning from that history, as our initial reaction with this new Covid-19 virus was of utter amazement. Still a lot lessons could be learned if we could visualize the after effects of the last pandemic of 1918.

Viruses fall on the borderline of living and non living.
They are strange as:
1. Do not have cell, a basic structural & functional unit of life to claim it as living organism,
2. Do not have their own metabolism of any kind, as do not possess any cell organelle,
3. Do not reproduce by any form of cell division,
4. Do self assembly only in a host cell, creating their multiple copies on the expense of host cell,
5. The only living characteristic they possess is gene, either in RNA or DNA strand form. They can not synthesize protein as they lack Ribosome, a cell organelle for the translation of viral mRNA,
6. The nucleic acid in RNA or DNA form alone is capable of infecting host cell even after being crystallized and stored for years in abiotic conditions. If and when that comes in contact with any host cell, starts behaving as a copy machine, producing of their own kind and consuming/killing the host cell.

Virus name in various Indo-European languages like Latin, Ancient Greek, Avestan means poison or poisonous substance, originating from Sanskrit root 'Visa'. 
Much before the discovery of structure of virus, it was identified as the poisonous substance rather than some biological entity.

Some specific features of viruses:
1. Viruses are submicroscopic in structure, shape ranges from helical to icosahedral to many more complex forms, invisible in the light microscope, as they are one-hundredth of the size of bacteria.
2. In nature their number is 10 times higher than the Bacteria.
3. Bacteriophage is a virus infecting to bacteria. 
4. Tobacco Mosaic Virus was the first virus discovered by Dmitri Ivanovsky in his 1892 experiments just at the end of the nineteenth century.
Wendell Stanley later studied the virus, managing to extract it in the form of pure crystals and show that it is composed of protein and ribonucleic acid (RNA) in 1935 and was awarded Nobel Prize in 1946.

Viruses consist of a long chain of either DNA or RNA, a protein coat Capsid surrounding and protecting the central genetic material and in some cases a lipid envelope surrounding the nuclear capsid.

Genomics of Viruses:
Of all the viruses found, about 70 percent are of RNA types genome. Due to possible higher rate of error in enzymes responsible for replication in RNAs type, they show much higher rate of mutation than to DNA viruses. That causes much higher rate of variant and that means the great adaptability to the new host.

The viral RNA may be of two types:
Single stranded (ss) or Double stranded (ds), they further vary as occupying on single RNA segment or two or more segments.
Genomes on single stranded RNA may further be of 2 types:
1. a sense strand (plus strand), which can function as mRNA; they alone can replicate if injected into host cell.
2. anti sense strand (minus strand), a complementary to sense strand, can not function as mRNA, no translational function, can not produce viral component.

The retrovirus genome comprises two identical plus-sense ssRNA molecules.
Most DNA viruses contain a single genome of linear dsDNA.

SARS-CoV-2, a corona virus causing Covid-19, is a RNA virus, and it must infect a host cell to replicate itself.
Error during the replication of viral RNA resulting in similar but not exact copies of the original, causing mutation. These mutant viruses called variants, which differ by single or many mutations.
A variant is called strain which shows distinct physical properties, behaving differently from the parent virus.
 
Following are the common variants of Covid-19 which are also strain; each containing several different mutation:
1. UK variant (B.1.1.7)
2. South African variant (B.1.351)
3. Brazilian variant (P.1)


Delta plus variant of Covid-19 is a warning that SARS-CoV-2 is continuing to evolve.
 
When new organisms enter the human race, they learn and adapt quickly to us. Unless we learn and adapt too, we're going to have more problems in the coming months and years. The virus is not done with us yet.

WHO says: 'When a virus is widely circulating in a population and causing many infections, the likelihood of the virus mutating increases. The more opportunities a virus has to spread - the more replicates and the more opportunities it has to undergo changes.'

Note: On the site of  WHO , this has been explained with a nice illustrative video to understand the mutational change in Covid-19 virus genome to form the newer variant. 
Following screenshots are shared thankfully from the above said video put in public domain to understand the possible change in four bases of the RNA's; i.e. Adenine, Guanine, Uracil, Cytosine. 










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