New viruses: Coronavirus and SARS disease

Cases of severe acute respiratory syndrome, or better known as SARS (Severe Acute Respiratory Syndrome) still place headlines in most of the world’s mass media. And even day by day people are increasingly panicking because the number of patients continues to grow, while there is no way to overcome them. WHO has appointed 11 laboratories in various countries, including the Tokyo Institute of Infectious Diseases (NIID) and The Center for Disease Control and Prevention (CDC) -Atlanta, to examine the virus that causes it. Initially researchers in China said that the cause was Chlamydia bacteria. But after that researchers from Hong Kong and several researchers from other countries suspected that there were two possible causes, namely Coronavirus and Paramyxovirus. After going through a long period of time, finally WHO announced that the mastermind of SARS was Coronavirus.

Coronavirus and SARS disease

Analysis of the search for the cause of SARS is done by isolating the virus from patients suspected of having SARS. Certainty against Coronavirus is due to the discovery of this virus from SARS patients. The analysis carried out included analysis by microscopy, PCR and sequencing. The results of microscopy and PCR analysis confirmed that the virus concerned was Coronavirus, but the results of the sequential analysis found differences between Coronavirus from SARS patients and Coronavirus found so far. This difference in sequence raises the prejudice that the possible virus that causes SARS is a mutated Coronavirus. Because of this difference, specifically for Coronavirus that causes SARS, it has been given a new name, the SARS virus.

What is Coronavirus?

The word “Corona” comes from the Latin meaning crown or crown. This is in accordance with the form of Coronavirus itself which when viewed with a microscope looks like a crown (see picture). The shape of this crown is marked by the presence of “Protein S” in the form of shoes, so it is called a spike protein, which is spread around the surface of the virus (arrow). “Protein S” is what plays an important role in the process of virus infection in humans.

Microscope image of Coronavirus. Taken from the home page of Queen University Belfast, UK). Appears on the arrow “Protein S” around the surface of the virus to make the virus shape like a crown.

Coronavirus is a round virus with a diameter of around 100-120 nm. Therefore, prevention of Coronavirus infection will be effective when using masks that are porous smaller than 100 nm.

This virus was first isolated in 1965, from a child’s nasal discharge which showed symptoms of a cold (common cold), which is usually caused by a Rhinovirus infection or influenza virus. And, in fact, it is indeed very difficult to distinguish between the symptoms of Rhinovirus infection, Influenza virus and Coronavirus.

This is also an obstacle in determining the virus that causes SARS. Because if a virus is found from a patient who is not suffering from SARS and it is stated as the cause of SARS it will result in a fatal error. That is, patient selection is very important for the determination of the virus that causes SARS.

This virus has positive RNA as its genome, and is usually often called an RNA virus. Viral mutations occur at the time of replication and RNA viruses mutate about 1 million times faster than DNA viruses. If the DNA virus has a mutation speed of 10-8 to 10-11 nucleotides each time the replication process, the RNA virus has a 10-3 to 10-4 density. Therefore, it cannot be denied that the virus that causes SARS is a mutated Coronavirus.

Coronavirus genome length ranges from 27 to 32 kilobasas. This genome forms viral body building proteins such as phosphoprotein N, glycoprotein M, protein E, protein S, and glycoprotein HE, and proteins or enzymes needed for replication of the virus itself.

Besides infecting humans, Coronavirus also infects animals such as pigs, dogs, cats, mice, rabbits, cows, and chickens. In these animals, this viral infection generally also causes respiratory symptoms (pneumonia) as well as in humans.

However, this virus is very host-specific, so Coronavirus that infects one animal only infects the animal. The virus cannot infect other animals and even humans. This virus is unstable in the air, and can only live for 3 hours, so there is very little possibility of airborne transmission. Most likely the transmission of this virus is through sneezing or coughing from an infected person to someone close to him.

Coronavirus replication

Most Coronaviruses only infect cells from their parent species and species that are closely related to their parent. In these stem cells, Coronavirus can only multiply in certain tissues. That is, the cells and tissues for breeding this virus are very specific. This specificity is determined by the nature and distribution of the receptor molecule from the cell and the variation of the “Protein S” sequence from the virus itself.

Coronavirus replication takes place in the cytoplasm of cells and this virus can also multiply in cells that have already taken nucleus (enucleated cells). In experiments outside the body (in vitro), actinomycin D can inhibit the replication of Coronavirus in cells. But there are no studies on the effectiveness of these antibiotics clinically. Therefore, there is no decision whether antibiotics can suppress the proliferation of this virus in the human body.

The Coronavirus replication process can be simply explained as follows. The virus first binds to cells through interactions between “Protein S” and receptors. After that the virus enters the cell and the viral RNA genome comes out of the viral membrane. Then part of the RNA genome functions as mRNA and partly as a template for negative RNA synthesis. The genome that functions as mRNA is translated into various proteins. Among these proteins, some of which function to form the body of the virus and some that function for the process of replication / multiplication of RNA. While some other RNA genomes are used for negative RNA synthesis. This negative RNA is then used as a template for positive RNA synthesis. And so on this process takes place repeatedly. With this process, finally the positive RNA that becomes the genome will multiply. The positive RNA that has been multiplied is wrapped by viruses that make up the body of the virus, so new viruses are formed (progeny). This new virus finally comes out of the cell and has a function as a normal virus that can infect the next cell.

Coronavirus mutation

RNA virus mutations, not just Coronavirus, usually occur during the RNA replication process. In this process, negative RNA is synthesized from positive RNA or vice versa. This synthesis is carried out by the enzyme RNA polymerase and the sequences of synthesized RNA are those that complement the template. At the time of this RNA synthesis, RNA polymerase is sometimes misread so that what is formed is not a sequence that complements the template. As a result, the sequence formed is mutated.

For DNA viruses, where DNA polymerase is at play, the same error occurs. But this error can be fixed, because for DNA replication there is an enzyme exonuclease that functions as “proof-reading” or “error correction”. That is, if there is a synthesized sequence that does not complement the template, this exonulease enzyme will get rid of the sequence, and only then the synthesis process will proceed again.

This difference actually causes the RNA virus, which includes Coronavirus, to mutate much faster than the DNA virus.

Now the extent to which Coronavirus is suspected to be the cause of SARS is mutated. The results of a team analysis from The Centers for Disease Control and Prevention (CDC), United States, showed that protein genes from proteins that make up the body of Coronavirus that causes SARS are very different from Coronavirus known during this, compared to viruses that infect humans and animals.