Features of Virus
To understand antiviral medicines we need to understand some main features of the virus. The virus isn't a complex organism; it only consists of the outer membrane, RNA, or DNA as genetic material, and a few other proteins. Similar to every living thing virus tends to multiply itself infinitely, although they can't achieve multiplication on their own. Due to the unavailability of some major organelles in their own anatomy, they need a host cell.
Viruses use host cells to multiply themselves. When a virus production in a cell gets mature they attack other cells of the organism to carry on their multiplication process further. Most of the antiviral medicines try to stop this multiplication, it could be achieved by targeting several key processes and elements in the cell by the medicines.
RNA/DNA is the most important organelle in each virus's anatomy, as well as all living organisms, DNA is a series of building blocks (nucleotides) in a fixed pattern. To multiply itself the first thing the virus needs is to copy its own DNA for its offspring virus. Copying of DNA is done in the host cell using all its utilities. The synthesis of DNA consists of assembling individual nucleotides into a chain. Many special enzymes are utilized in this assembly of proteins.
Remdesivir is popularly used to cure hepatitis C and the Ebola virus disease. The general functioning of the drug is to stop the multiplication of the virus in the host cell. Disruption in the reproduction of the virus is achieved by terminating the basic sequencing function of the RNA. Sequencing function is common among all the viruses therefore the effect of this medicine is evident on almost all viruses, hence it is known as broad-spectrum antiviral.
In the host cell when the virus multiplies itself, it needs to polymerize (the process of making a chain of molecules) the long DNA/RNA molecule. To polymerize RNA it needs four types of building blocks; adenine, guanine, cytosine, and uracil. Remdesivir provides analog molecules for one of the building blocks, these molecules disrupt the sequencing process by resembling uracil molecules.
An enzyme known as 'RNA-dependent RNA polymerase' (RdRp) picks up building blocks and sequences them according to the master copy in the host cell. This enzyme mistakenly picks up a remdesivir molecule instead of uracil and tries to arrange it in the sequencing process. Remdesivir molecule adheres to the enzyme permanently and blocks this enzyme, thus further sequencing is stopped.
This drug is being used in covid-19 patients to slow down the reproduction of the virus in the cells. This drug neither kills the virus nor it can completely stop the reproduction process. It just gives some time to the patient's body to prepare.
The purpose of the virus to enter the host cell is to reproduce When the virus's genome(RNA/DNA) enters the host cell, RNA/DNA tends to generate multiple copies of itself. Copies of RNA will be used to make multiple copies of the virus.
RNA copies are made by the sequencing process of building blocks with the help of RdRp. RNA building blocks(nucleotides) are arranged in the same sequence as it is in the master copy. Before making an exact copy of the genome a template is made using the same building blocks. The template will be used to make copies of the original RNA.
RNA strands are made from four types of nucleotides; Adenine, Guanine, Cytosine, and Uracil. There might be thousands of nucleotides in a single strand of RNA. Template of RNA strand grows by the 'pairing rule'; adenine(A) always pairs with Cytosine(U), and Guanine(C) pairs with Uracil(G). Let an original RNA strand be 'AGUGGAACU' (each letter depicts a nucleotide). According to the rule, the first 'A' in the strand will pair with a 'U', the second 'G' will pair with a 'C', and so on. This process will generate a strand; 'UCACCUUGA'. Clearly, this strand is not a copy of the original strand, however, it will act as a template or a die for making copies of the original strand.
Now RdRp will use this template strand('UCACCUUGA') to make copies of the original RNA. The rule for sequencing again will be the same as above. The first nucleotide 'U' in the strand will pair with an 'A', the second nucleotide 'C' will pair with a 'G', and so on. In the end, we will get 'AGUGGAACU', the original RNA!!
Favipiravir in this process acts to confuse nucleotide'U' and 'C'. Both the nucleotide('U'&'C') consider favipiravir molecule 'F' as their pair. If we consider the same above example again then the third, eighth, and ninth positions are prone to error. if the third and ninth nucleotide in the original RNA considers favipiravir 'F' as its pair, then the template will end up as 'UCFCCUUGF'. This template may generate an RNA strand as 'AGCGGAACC' or 'AGUGGAACC' or 'AGCGGAACU' or 'AGUGGAACU', (we have considered that F is absent in the second sequencing process, otherwise, it may create more errors in sequencing processes.). These errors might lead to the termination of unfinished RNA sequencing, or at least it will end up in RNA with lots of errors. Faulty RNA will produce a virus with lots of mutations and hopefully not able to reproduce further.
Favipiravir is already an approved drug in Japan for influenza, and similar to remdesivir it does not stop the reproduction completely.
Function of favipiravir and process of sequencing in detail
Tocilizumab does not directly attack the virus, instead, it is an immunosuppressant. This drug functions as an 'IL6 receptor blocker'(Interleukin 6 receptor blocker). Interleukin is a protein that is produced by our immune cells as a signal. Receptors are bonding sites for interleukin on cell membranes.
Interleukin 6 (IL6) is involved in giving out pro-inflammatory signals to other cells when an infection is detected. When covid-19 infections reach a critical stage immune system may trigger these IL6 signals which will initiate inflammation in the lungs. Lung inflammation at this stage in the covid-19 patient is more damaging for the health as it restricts respiratory processes.
Cells that are involved in the inflammation process have special bonding places(receptors) on their cell walls. These receptors are designed for IL6 signals, when IL6 comes in contact with these bonding sites it is a signal for cells to start the inflammation process. Tocilizumab drug blocks the sites where IL6 could make a bond hence the drug is known as an IL6 receptor blocker.
Along with pro-inflammation signals, IL6 acts on other types of cells for other immune-related functions. Tocilizumab blocks other IL6 receptors irrespective of which type of cells they are. This blockage of sites on different cells may hamper some other immune functions of the body. That is why this drug is known as an immunosuppressant. The drug checks the inflammation of the lungs but it also makes the body prone to other infections.
mucormycosis is a fungal infection that became an epidemic in India after medicines like these and steroids were administered for a long period to covid-19 patients. Immunosuppressants like these make the body fragile which couldn't stand infections like black fungus.