In the past few months, the world has come to a standstill with the onslaught of the unprecedented pandemic caused by the SARS-CoV-2 a coronavirus, being the second of its kind encountered in the 21st century. This virus belongs to a family of viruses shaped like the outer layer of the sun, and hence the name.
What is so fearful about this particular viral infectious disease is the ease of its transmission across communities through populations and the fact that the mortality upon infection is not specific to a particular age group of the population. To develop strategies for vaccination or cures, we have to primarily understand the virus, its fundamental structure, mechanism of infection, and transmissibility.
GENOME AND STRUCTURE
A virus is “Simply a piece of bad news wrapped up in protein” a description used by biologists Jean and Peter Medawar in 1977(‘Bad news wrapped up in protein’, Jonathan Corum and Carl Zimmer, New York Times, 3rd April 2020). Viruses serve as the link between the animate living and the inanimate non-living, only able to show any true signs of life including the capacity to reproduce only inside living cells.
The SARS-CoV-2 virus belongs to the broad category of viruses called RNA viruses that as their name suggests, utilize ribonucleic acid as their chief genetic material. Fortunately, unlike DNA, RNA is generally more vulnerable to physical agents. Also, RNA viruses show higher degrees and rates of mutation as compared to DNA viruses. Hence more often than not, they can make the jump between species barriers as seen in the case of SARS-CoV-2. The outermost layer of the virus is constituted by a lipid membrane studded with a multitude of structural proteins. This coat shields the integral genetic material (RNA) from damage that can be caused due to external factors.
In January, the SARS-CoV-2 genetic set of instructions, the genome, was sequenced from a 41-year-old man who worked at the seafood market in Wuhan, China. The genome of this virus was found to be 30,000 bases long which is infinitesimally small in comparison to the gargantuan, 3 billion bases comprising the human genome. These 30,000 letters (nucleotide bases) comprise the multiple genes of the virus that code for a variety of proteins that perform a number of integral functions upon infecting a host cell. Proteins are the critical functional units’ at the most basic level, responsible for performing the cellular functions.
Scientists have already discovered 29 odd proteins coded for by the genome, the first 16 of which are all coded for by the first gene, which is seen to be truly novel.
This virus functions like an extremely well organized, but complicated machine through these very proteins, all playing different, yet key roles in the life cycle of the virus inside the host cell.
These functions include (all processes separately handled by individual proteins):
Sabotaging the cell’s production of its native proteins.
Preventing assembly of anti-viral host cell proteins and genetic camouflage against the same.
Un-tagging and cutting the long-chain polypeptides coded for, at specific points so that the new viral proteins formed can perform their respective roles.
Bubble making i.e., forming fluid-filled bubbles within infected cells that are the locations for new copies of the virus to be constructed.
Copy assistants required to replicate the viral template genome within the host cell.
Accessory proteins that enable the virus to escape after its reproduction and assembly by bursting out through holes created in the plasma membrane of the host cell.
CHARACTERISTICS AND OTHER PROPERTIES
One of the peripheral, structural proteins coded for by the genome is the ‘S’ spike protein, which is one of four such proteins covering the capsid of the SARS-CoV-2 virus. This protein helps the virus by attaching itself to a particular receptor protein called the ACE-2-receptor (Angiotensin Converting Enzyme) present on the outer surface of cells lining the lung.
A common question asked is with regards to how long a virus can remain on a solid surface. With respect to the surface stability of SARS-CoV-2, experiments were conducted utilizing aerosol, plastic and stainless steel, cardboard, and copper wherein a measured number of viral particles were placed in each medium and the time after which no viral particles were present on the surfaces was measured. It was seen that viable SARS-CoV-2 titer values were observed after 72 hours on plastic and after 48 hours on stainless steel. For cardboard, on the other hand, the time duly noted was 24 hours, and that for copper was 4 hours. This experimental data was conclusive of the fact that the virus was more stable on the surfaces of plastic and stainless steel than on cardboard and copper. This was further indicative of the following facts:
Reinstating the fact that copper is previously known for its excellent microbicidal activity, also provided a surface on which the virus could not remain for long owing to certain surface chemical interactions between the copper atoms and viral particles. It might make sense to use copper either for surfaces or utensils.
The virus particles were also found to remain viable for many hours even in aerosols and this was indicative of how easily transmittable the virus was through the air.
This also was conclusive of the fact that epidemiological characteristics of these viruses arise from other factors including high viral loads in the upper and lower respiratory tracks, for the potential transmission from people infected to transmit the virus asymptomatically.
Treating an infected person using antiviral drugs is, without a doubt, essential as seen in the use of ‘Remdesivir’, an antiviral that disrupts viral replication. However, as the clichéd saying holds well – “Prevention is better than cure”, vaccination might represent the best strategy to control the spread of the virus. The basis of using a vaccine is to elicit a protective antibody response to the pathogen.
Vaccines are of many types, the three main being:
· Live-attenuated vaccines (attenuation being the process of reduction of the virulence of the virus) that consist of live individual viral particles that upon bearing passage (a process enabling attenuation) are less virulent. However, there is always a narrow risk of reversion and re-infection of the patient.
· Inactive vaccines that consist of the killed viral particles that bear no risk of reversion and thereby re-infection.
· Conjugated vaccines that combine a weak antigen with a stronger antigen, trying to elicit or evoke a response by the immune system towards the weaker antigen.
All of these older methods employ the means of isolating the virus or one of its spike proteins and purifying it. However, a more modern, cutting-edge technique involves using short copies of the pathogens’ genetic code which can then produce only the coat proteins within our bodies. However, to date, the regulatory authorities like the US-FDA (United States-Food and Drug Administration department) have not approved of a vaccine made by this method. Hence the success of such a vaccine for SARS-CoV-2 would be revolutionary in the field of medical biotechnology.
To prepare a vaccine ready for use by the general population, three major steps have to be followed:
· Phase 1 – Development of the vaccine candidate using technologies that can produce purified versions of the coat proteins in sufficient quantities.
· Phase 2 – Clinical trials that require the most time to complete and generally cannot be sped up or hastened in any way (usually take 8-12 months for completion). This includes testing for safety and efficacy sequentially.
· Phase 3 – Scaling up manufacturing for worldwide use.
However, even after successful completion of all three steps there remains the considerable challenge of getting governments and people to make sure that all people needing the vaccine are able to receive it.
In terms of technicalities, having listed out these many points, I am of the opinion that designing a vaccine that can prevent the immediate binding of the spike protein ‘S’ to the ACE-2 receptor would be the best way moving forward. Furthermore, it might be invaluable if serological tests could be run on a large scale to check whether the person in question is already positive for the antibody to SARS-CoV-2 virus due to prior asymptomatic infection.
Now what we all must do is remain informed and make educated choices with all this information, hoping for the best.
By Rajeev Harsha Shreedhar
Fourth Semester Student of Biotechnology Engineering, B.E at M.S Ramaiah Institute of Technology, Bangalore.
· Bad news wrapped up in protein, by Jonathan Corum and Carl Zimmer, New York Times, 3rd April 2020.
· ‘It’s a razor’s edge we’re walking’: inside the race to develop a coronavirus vaccine, by Samanth Subramanian, The Guardian, 27th March 2020
· Aerosol and Surface Stability of SARS-CoV-2 as compared with SARS-CoV-1, by Dr.van Doremalen, Mr. Bushmaker, and Mr.Morris, The New England Journal of Medicine, 17th March 2020.
· Coronavirus Structure, Vaccine and Therapy Development, By Jonathan King and Eric Sundberg, Biophysical Society, 19th March 2020.