Drug Discovery and Development for Treatment of Coronavirus Infection

Keywords: coronavirus, antiviral drug, immune system, secondary metabolites, synthetic analogues, granuloma

In the fight against the spread of coronavirus, it is reassuring to know that pharmaceutical companies are racing towards the development of a vaccine which has been forecasted to be available to the public in about a year from now. As good as this sounds, people fear that this infectious disease could become a global pandemic before the vaccine is available. According to several reports, the death toll from this infection is rising daily with the number of the elderly and people with underlying health conditions accounting for 90% of mortality. Clearly there is an urgent need to begin the development of therapeutics to treat this infection to slow down the mortality rate. There are two options on the table; to develop a drug with viricidal properties that is able to destroy the virus without damaging the host cells or an antiviral drug which inhibits the proliferation of the virus, with the hope that the body’s immune system will eventually destroy it by the end of the treatment.

A few weeks ago, the Chinese government celebrated some people in Wuhan who have recovered from the infection. They tested negative for coronavirus after a month of isolation even though they had no access to specialised medical treatment. Many other survival stories have also been reported across the globe. This fact gives scientists the assurance that given a strong immune system, the body can eliminate this virus in a matter of four weeks. Now we know we are not dealing with a virus such as HIV which the body is unable to eliminate because it tends to infect the very white blood cells designed to destroy it. Also, we know that virologists don’t fully understand the nature and behaviour of coronavirus yet, which means we can assume that it will be quicker to develop an antiviral drug than to develop a virucide. The problem is the fact that the conventional method for drug discovery and development is time consuming and scientists are very cautious to consider an alternative route because of fear of the unknown or perhaps the lack of funding in another area.

Herbal scientists with their knowledge of herbal medicine can offer a quicker alternative route to support the development of this antiviral drug especially at the initial stages where candidate synthetic molecules will be screened for potential drug leads. We know that plants produce compounds known as secondary metabolites to combat and protect against environmental disturbances such as external stress, diseases and predators. These bioactive compounds are very important to humans in fighting diseases. This explains the discovery and development of drugs like morphine (from poppy seeds), quinine (from cinchona tree bark) and aspirin (from willow tree bark). Selected plants by herbalists can be infected with coronavirus in a controlled environment, the numerous secondary metabolites the plants produce as a result of trying to fight this infection can be extracted, isolated and analysed to determine their molecular structures. The structures can be copied to derive synthetic analogues to be assessed for potency. Plants can be infected by integration of transgene (non-pathogenic bacteria carrying coronavirus gene) into plant cells. This type of plant engineering has been used to produce plant-based vaccines in the past however none of these vaccines were licenced by US Food and Drug Administration (FDA) as they were classified as under genetically modified crops category.

To develop an antiviral drug to treat coronavirus infection, we need to understand the aetiology of the disease. We have clues from the symptoms which include fever, cough, sneezing, shortness of breath and in severe cases pneumonia. There is no doubt that this is a respiratory disease and we can assume that the virus becomes infectious by inhalation, the reason why people are wearing masks for protection. The aetiology is likely to follow the pattern that the virus enters the airways, the body recognises it as foreign and activates macrophages in the lungs for phagocytosis. These macrophages recruit monocytes to form ‘’granuloma’’ a process where the immune system walls off infected areas with fibrous proteins such as keratin. When coronavirus is stable inside the granuloma, it remains dormant, resulting in latent infection. Pathogens can survive within granuloma for weeks or even years, in the case of coronavirus, scientists are speculating survival (incubation period) only lasts two weeks hence the reason why suspected cases are being quarantined for this length of time. Prolonged dormant phase allows the virus to avoid the host response until its entry into infectious cycle arising from compromised immune responses. This is when the individual starts to show symptoms and infectious coronavirus can be released back into the airways to be expelled and transmitted to another person. With this understanding, pharmaceutical companies can use human macrophage infection models during in-vitro tests for potency of the synthetic analogues. It will also allow them to bear in mind that the drug needs to target the airways especially the lungs before development reaches in-vivo tests and human clinical trials.

It’s obvious that surveillance testing for coronavirus infection has not been very effective. In many places, only people showing symptoms indicating infection are being tested and many have been given a false negative diagnosis. This problem caused by latent phase of infection can be solved by developing a substance/drug that can penetrate the granuloma to activate the dormant virus so that infection can be diagnosed at the very onset. If this substance becomes available before the actual antiviral drug, the only ethical argument that could disapprove its use would be that this substance would increase the chances of infection. However, when an antiviral drug or a virucide is available, this substance can be used in testing a larger population irrespective of visible evidence of clinical symptoms of the infection.

In summary, there are many plants and many varieties/genotypes of plants that can be used in this discovery and development process. This means several potent plant compounds can be isolated for analyses. Even though we know that only a few candidates pass clinical trials with very few to minor side effects, the wealth of information collected can allow scientists to prepare for the inevitable appearance of multiple strains of the virus. Anti-coronavirus drug candidates are expected to have the ability to block fatty acid synthase, inhibit RNA polymerase and inhibit virus cell wall development therefore, pharmaceutical companies should consider drug contraindications during this development.