Potential avenues of COVID19 drug research
Do you know how many proteins are possessed by COVID19? It’s 29 only when compared to a plethora of proteins contained in the very sophisticated species, Homo sapiens. Twenty nine proteins has the ability to conquer enough human cells leading to a catastrophic effect on the world. We cannot underestimate the power of the viral proteins.
Only way to bring an end to the viral activity either by — a drug or vaccine- is by blocking these proteins from hijacking, suppressing and evading the cellular machinery in humans. Unlike bacteria,these viruses have lesser number of weakness to be exploited. The fight is still ON. Several 100 drugs are under investigation to bring relief to the affected and on-the-verge-of-getting affected population.
Another set of clinical researchers are continuously working on the pathways taken by the proteins to interact with human cells. The target is to get a drug which will act on the host rather than the virus because the virus makes use of the host machinery by their tricks for their replication and multiplication.
To stop the viral activities from releasing orders to the human cells, the drug must have the potential to destroy the already affected human cells. This will open up many possibilities of drug targets in the host but it comes with a challenge too. It will be tough for the drug to differentiate between human cells and virus-hijacked cells. Now let us discuss the possible routes of attack which may unfold the mechanisms of action of a drug.
Prevent the virus from making an entry into the cell- The spike proteins on the viral membrane attaches themselves to the ACE2 receptors found in human cells. Plenty of them are found in the lungs and then in gastrointestinal tract. Lot of similarities in the spike proteins have been found in COVID19, SARS and MERS thereby making it advantageous for researchers to revise the strategies applied for SARS and MERS to combat COVID19. The Moderna vaccine is one such example.
The spike proteins have also helped scientists to evaluate the probabilities of antibody therapy. Moreover, it is a non-Herculian task when compared to the development of a new drug as it deals with the power of the human immune system. (The immune system has the expertise of producing antibodies to act on foreign viral proteins). Based on this, many hospitals are trying to infuse antibody-rich plasma from COVID19 survivors to existing patients.
This is interesting to know that merely an attachment to ACE2 receptors will not allow the virus to enter human cells. Another step comprising the activation of the spike proteins comes into place. This happens when the human enzyme called furin comes along and triggers the activation process. Once the process is completed, it gains entry into the cell via endocytosis. Many candidate drugs, like hydroxychloroquine, are based on inhibition of the spike-activation process.
Put a full-stop to the replication of the virus- When the viral RNA is inside a human cell, it gives orders to the cell to produce more viral proteins to make more viruses. As the naked COVID19 genome resembles a RNA, the human cell cannot distinguish between the viral genome and human RNA so it is bound to obey the instructions given by viral RNA.
Replication, being a very complex process, offers numerous potential targets for drugs. An experimental candidate drug, Remdesivir, which is in clinical trial acts by targeting the viral protein that copies the RNA. Now there are proteases (other viral proteins) which helps to free off individual viral proteins from the strand and help the virus to replicate. In addition to the above proteins, the virus has mysterious ‘accessory proteins’ which are believed to allow the virus to evade the human cell’s natural antiviral defense-another potential target for a drug.
Prevent the immune system from going out of control- Doctors have noticed that the critically ill COVID19 patients experience a cytokine storm in which the human body sparks a rush of antibodies to fight against the virus. Contrary to what is expected, this storm causes further damage to the lungs by fluid accumulation inside the tissues.
So another possible target is the immune system than the virus itself. As cytokine storms are very common in autoimmune disorders and bone marrow transplant cases, the drugs that treat the immune system rush are also under investigation for COVID19. Now this also needs to be balanced with clearing the virus from the body.
Much of the current research is into testing the existing drugs because these drugs will become more easily accessible at an early pace in hospitals. The pros of these drugs are that the side effects are already known and the companies are well equipped with the facilities.
“We just need to make a beginning”.
