By Don Syiem & MB Syiem
Corona virus which has taken the world by storm of late is named so because of its crown structure. The purpose of this write –up is to present the few known facts about this virus in a nutshell. To begin with a virus isn’t “alive” in a typical sense. It’s just a collection of genetic material (DNA or RNA) and a small toolbox of proteins. The blueprint for the structure and functioning of a virus is contained in its genetic material while the proteins are used to perform two selfish tasks: 1. to get inside the cells of its host and 2. to hijack that cell’s own genetic machinery in order to produce thousands of copies of itself.
Since it can’t move on its own, a virus must piggyback its way across the globe through its hosts. Respiratory viruses like Covid-19travel primarily through respiratory secretions — the dribbling nose, sneeze or the cough. A cough or a sneeze produces a turbulent puff cloud that expands as it spreads. Because exhaled air is warmer and moister than room air, it billows out, carrying with it different-sized snot particles.These airborne particles can either be directly inhaled or end up in the eyes- the most direct and contagious way of catching a virus. Once the particles fall from the cloud and settle on public surfaces like door handles, etc., they then depend on human hands to provide any further transportation.Covid-19 survive inside their little mucus condo for a number of days, but their infectivity tails off sharply after a few hours. Non-porous surfaces like stainless steel and plastic slow the drying process and give the virus added time.
COVID-19 which is SARS-CoV-2 belongs to the genus beta-coronavirus carrying the largest genomes among all the RNA virus families. The virus has a few key features. These include: 1. A protective protein shell, or capsid 2. A nucleic acid genome (RNA), tucked inside of the capsid 3. A layer of membrane called the envelope. Its genome sequence is the complete list of the sequential arrangement of the four different chemical entities called nucleotides (abbreviated as A, C, G, and U) that makes its RNA genome.For a successful invasion, the corona virus needs to find a precise protein (a “receptor”) on the cells that line the human respiratory tract. These proteins exist to allow the cell to interact with its surroundings, but the virus takes advantage of them for its own purpose. A virus’ ability to enter the human body has two key variables: location of that receptor, and how strongly the virus binds to the receptor. If the virus binds tightly to its preferred receptor, the victim only needs to be exposed to a small number of viral particles to get infected. When it infects host cells, it replicates its genomic RNA (gRNA) and produces nine smaller RNAs known as subgenomic RNAs (sgRNAs) that are used for synthesizing variousproteins- spike protein (S), envelope protein (E), membrane protein (M), nucleocapsid protein (N), and several accessory proteins. The gRNA is packaged by the structural proteins to assemble progeny virions which burst out of the host cells and repeat the cycles of infection.
Diseases like SARS, MERS, and COVID-19 are all thought to have originated in bats, then moved to humans via another animal. Viruses are subjected to genetic alterationsin two primary wayswhich determine their infectivity. 1. Errors made during the replication process called mutations. And RNA viruses in particular are known to be bungling replicators as they undergo a lot of mutations.Since viruses reproduce in such massive numbers, eventually a “winning” combination comes up and a new viral strain is born. 2. The second way that viruses can acquire new infective capabilities is known as “reassortment” i.e.when a mammal has the misfortune of being infected with two (or more) respiratory viruses simultaneously, then as these viruses replicate, their genome parts can be shuffled together and then recombine/exchange. An example is H1N1 virus which combined the swine, human and an avian influenza (triple reassortment). That’s how the swine H1N1 pandemic was born.
There are two major factors that affect infectivity: 1. the virus’s innate ability to infect a host i.e. how capable is it of finding and binding to a suitable receptor in the lung. 2. ability to reproduce. A healthy-but-infected host is a Trojan horse unwittingly spreading the virus.
Mortality of any viral disease is calculated by dividing the number of patients who died by the number who have been infected. Mortality rates tend to range higher early on in an outbreak, because the denominator is falsely low. Without accurate diagnostic testing, the number of patients infected includes only those with obvious symptoms. This seems to be the case with COVID-19. Since symptoms alone make for a sketchy denominator, public health officials rely on lab verification of infection, but historically, viruses have been difficult to detect. Because they are hard to grow in a lab, the next best step is to look for antibodies against the virus. Unfortunately that can be inaccurate too as it often misses early infections because the body has yet to mount an antibody response.
In a diagnostic laboratory virus infections can be confirmed by a multitude of methods. These include: 1.Viral culture 2. Antibody test 3. Viral DNA or RNA detection test.In recent times Reverse Transcription-Polymerase Chain Reaction (RT-PCR) has become the techniqueof choicefor virus detection. The technique is the combination and convergence of genetics, virology, laboratory science, computer power, and international data-sharing. PCR basically detects genetic fragments of the virus.The process begins with constructing a primer (a short nucleotide strand which is highly specific for binding to the viral genome). The primer is designed with the help of bioinformatics tools and software. This primer binds to the viral RNA and is necessary for synthesizing the complementary DNA strand referred to as cDNA. It is this cDNA which is amplified in a thermocycler. The reaction is allowed to proceed in a cyclical manner which ultimately results in the mass production of the viral DNA reaching a threshold or detectable limit. The success of real time PCR largely relies on the specificity of the primer binding to the gene of interest.
In case of Covid-19 uncertainty over whether it is the virus itself or the response of a person’s immune system that ultimately overwhelms a patient’s organs, is making it difficult for doctors to determine the best way to treat people who are critically ill. There are reports suggesting that the immune system plays a part in the deterioration and death of people infected with the new coronavirus, and this has spurred a push for treatments such as steroids that rein in that immune response. Some of the earliest analyses of people with the coronavirus suggested that it might not be the virus alone that ravages the lungs and kills; rather, an overactive immune response might also contribute. High blood levels of proteins called cytokines, which can ramp up immune responses have been reported. They include signaling protein called interleukin-6 (IL-6)which is a call to arms components of the immune system, including macrophages. Macrophage cells fuel inflammation and candamage normal lung cells.The release of cytokines known as a “cytokine storm”, also occurs with other viruses.Thus, collateral damage from the immune response may aggravate the illness.
There are no specific medicines available to treat COVID-19 as yet; desperate search for a vaccine and hundreds of studies are being carried out. For those interested they may look up – What Drugs May Fight Coronavirus COVID-19? Drug Trials, Treatments, Vaccines; reviewed by Charles Patrick Davis, MD, PhD (3/26/2020).
In conclusion,there is much to be researched about Corona viruses in order to come up with effective therapeutic measures to combat the pandemic.
References:
1.Wikipedia; 2.Genotype and phenotype of COVID-19: Their roles in pathogenesis.J Microbiol, Immunol and Infect. Available online 31 March 2020. 3. Complete Genome Sequence of a 2019 Novel Coronavirus (SARS-CoV-2) Strain Isolated in Nepal. March 2020. MicrobiolResourAnnounc. https://doi.org/10.1128/MRA.00169-20. 4. Coronavirus Genomic and Subgenomic RNA Architecture Mapped. April 13, 2020. 5. Nature, Vol 580, 16 April 2020, pp. 311-312.
- Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know. Downloaded from https://annals.org published at Annals.org on 31 March 2020.
(The writers are Professors, Department of Biochemistry, NEHU).