THERE’S no escaping the pervasive imagery of the ball-like shape we know as Covid-19, also known as SARS-CoV-2. The virus’ physical shape serves the sole purpose of delivering the genetic payload contained within, referred to as a genome, to the next host.
Once inside, the virus hijacks the host cells to make more viruses using the information encoded in the genome — the total genetic content of an organism. All livings things have a genome, and although viruses are not considered alive, they too have genomes.
The SARS-CoV-2 genome is composed of a chemical substance called RNA, very similar to DNA that we are more familiar with because the majority of organisms use DNA as the constituents of their genomes. The information encoded within the genome can be extracted by a process called genome sequencing.
This process generates large amounts of data in the form of the letters A, C, G and T, which are strung along in various combinations. Each letter is referred to as a nucleotide, the basic unit of a genome.
The genome of SARS-CoV-2 contains nearly 30,000 nucleotides. Humans have more than three billion nucleotides, many bacteria will have millions. The 30,000 or so nucleotides contain the information for synthesising about 30 proteins (as a comparison, humans have over 20,000 proteins).
In general, the genomes are analysed to identify variations, sometimes termed as mutations, also used to track the genetic footprint left behind by the virus as it transmits from host to host. Analysis of the variations can reveal the potential effects of the mutations on the virus’ capacity to infect its host and cause disease.
At the time of writing, more than 78,000 SARS-CoV-2 genomes have been sequenced the world over and deposited in a publicly accessible database — GISAID (Global Initiative on Sharing All Influenza Data) — including about 100 genomes from Malaysia.
It was the discovery of a specific mutation profile that led scientists to classify Covid-19 as a newly discovered (novel) coronavirus, distinct from its genetic cousin, SARS. Mutations point to SARS-CoV-2 being more adept at invading the human host, making it more transmissible than SARS.
On Aug 6, Health director-general Datuk Dr Noor Hisham Abdullah mentioned the possibility of the Sivagangga cluster viruses having what is referred to as the D614G mutation, referring to a mutation in the sequence of the spike protein at position number 614.
This mutation first emerged in Europe in February, and peer-reviewed research regarding the mutation was published in the journal Cell last month. That paper reported that there are now more Covid-19 cases carrying the G614 mutation than the original D614, suggesting that G614 is more infectious and spreading faster.
Of the genomes sequenced here, the D614G mutation has been detected in nine. These highly transmissible mutants are already on our shores. Malaysians must therefore adhere to the procedures in place. Complacency may lead to us being overwhelmed by these highly spreadable mutants.
It is still not understood why this molecular-level change results in a more infectious variant of the virus. Recently published studies in Nature and Science suggest that individual genetics play a role in the severity of the disease, brought about by the different ways an individual’s immune system is responding to the virus infection.
For severe cases, the evidence points to the immune system going overboard in responding to an infection, akin to the Malay proverb “marahkan nyamuk, kelambu dibakar“. Since the immune system is not able to figure out the appropriate response to eliminate the virus, it throws everything in its arsenal to rid the body of the invaders, resulting in more harm than good.
This points to the genetics and environmental circumstances of the individual hosts as being crucial factors that determine how each body responds to the infection or is affected by the virus. Therefore, the obvious next course of investigation to understand Covid-19 is to understand what sets all these individuals apart.
To do that, scientists would have to gather massive amounts of data that include genome sequences of individuals who have succumbed to Covid-19 together with those who have survived and are asymptomatic as comparisons.