Advances Towards the Development of Small-molecule Antiviral Therapeutics-Part 1

The human body is an intricate system and it is truly amazing to ponder how it overcomes the constant flow of challenges concerning its survival. The immune system plays a pivotal role in this aspect, especially dealing with destructive challenges to preserve the corporal health and wellbeing. Every single part of the body is tightly guarded by this immune system, defending the body from harmful stimuli. There are instances though, this protective wall fails, allowing a window of opportunity for external or internal disease-causing pathogens such as bacteria, fungi, and parasites to infiltrate into the body. One such type of pathogen is viruses. Viruses are the most ubiquitous microbes in the world and handy with efficient replication machinery to readily undergo multiplication in their respective hosts. The devilish beauty of viruses lies in their way of survival to persist through continual adaptation in different host-organisms, sensitizing to environmental changes, evolving and gaining fitness through beneficial mutations, and sometimes re-emerging over time. However, their ventures to replicate and survive in the host-organisms often lead to many types of virus-related complications or morbidities spanning from mild infections, to self-contained infections, and in certain instances to deadly pandemics such as Spanish flu, HIV/AIDS, SARS, and COVID-19. Despite the differences in morbidity and mortality rates associated with these different viral infections, the collective disease burden that they impose upon human inhabitants is significantly severe which consequently inundates the globe with a continuous health threat.

Failures in the natural resolution of viral-infection-triggered disease courses beg for medical intervention and this is where the vaccines and antiviral therapeutics play their indispensable role. Both of these vaccines and targeted antivirals are allies of the immune system. The primary purpose of vaccines is the prevention of viral infections and re-infections in the targeted host population, while the said purpose of therapeutics would be the treatment upon infection, though the emergence of preventive-purposed antivirals known as antiviral prophylactics is worthy of mention. Oftentimes, vaccines are designed to target an exposed component of the virion known as the antigen, such as the surface exposed spike protein of the SARS CoV-2 viral-particle which recognizes and interacts with the host cell surface receptor it eventually interacts for host cell entry. When it comes to the targets of antiviral therapeutics, they can be of any possible site directly affiliated to the viral replication cycle. Host cell components that are directly associated with the said viral replication cycle may be a choice when designing therapeutics and they rarely tend to develop drug-resistance in viral context, yet this could also possibly affect the normal physiology of the host, hence the possible undesired side effects. Therefore, viral components are most commonly targeted for the development of antivirals, and their design intends to selectively disrupt the viral replication stage of choice; viral-attachment to host cell-surface receptor, viral entry into the host cell, viral genome replication, and viral egress from the host cell. There are certain factors to consider when it comes to designing antivirals which primarily depends on the viral-target of choice.

So, let’s discuss that in the next chapter of this letter series.