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On the fastest path to finding a cure: COVID-19

March 30, 2020 | Expert Insights

Identifying the enemy

Every day, we hear world leaders like President Trump assuring a panicked and desperate population that the silver bullet to kill the coronavirus is within our grasp.  Fully aware of the deadly threat to millions of human beings, scientists are working frenetically for the elusive vaccine. In the interim, to keep the deadly virus at bay, health workers on the frontlines of the pandemic are using general treatment measures to control the symptoms. But the truth remains, there is no vaccine or cure, as of now.

A virus is a sub-microscopic infectious agent that replicates only inside the living cells of an organism. They can poison all life forms, from animals to plants and even microorganisms. They are essentially composed of genetic material contained within an organic particle that feeds on the host’s metabolism to reproduce viral particles. They are hardy and can travel through air, water, soil and aerosols, mutating furiously. Scientifically, they are not considered living organisms.

Bacteria are easy to fight with antibiotics as they store the molecular tools they need to replicate themselves within themselves. But antibiotics are useless against viruses as they hijack the metabolism of the host to create more copies of themselves. As per Diane Griffin, a professor of microbiology and immunology at the Bloomberg School of Public Health at Johns Hopkins University. “So it’s been harder to find drugs that target the virus but don’t damage the cell as well.” 

The viruses mutate so rapidly that specific treatments and vaccines, created to deal with one epidemic is useless for the next.  All the time and money invested in SARS and MERS vaccine is of little consequence in case of COVID-19.

The virus can remain inside the host and continue to replicate itself and infect others, even when the host is asymptotic. The delay is due to the body taking time to create new antibodies to deal with the threat and the symptoms like fever and inflammation are actually signs of the body fighting back. By then, either the host would be on the recovery curve, or if old and weakened by other ailments, it may be too late.

Lessons from earlier pandemics

Taking into account the genetic similarities between SARS-Cov-2 and COVID-19, scientists are trying to rejig drugs which proved effective at that time. The biotech industry had made considerable progress in making drugs for SARS and MERS. The previous research efforts enabled the scientist to quickly assess the severity and transmission potential of the new threat and develop countermeasures like slowing down the damage from the virus and expedite the body’s countermeasures.

Anti-viral drugs target the virus, its enzymes and surface proteins, without damaging the host. It tries to weaken the virus, preventing its ingress into cells or stop its replication.

Remdesivir, produced by Gilead Sciences worked with SARS Cov-2 and is being experimented with for COVID-19. Protease inhibitors like Lopiavir and Ritonavair,  HIV anti-virals, attack the enzyme of the virus, which makes the virus inert are also being tried in many countries and have been found effective. Some patients in Jaipur were cured by them.

Another defensive mechanism being researched is the creation of antibodies collected from engineered animals or recovered patients. These antibodies strengthen the human immune system enabling it to quickly identify the threat and start generating its own antibodies before getting overwhelmed. Interferons are drugs which help trigger the human immune system and have proved to be effective against persistent infections and were used in China as part of the treatment protocol.

The most effective vaccines are those that coach the human immune system to fight off the virus before it can infect the cells. But these need time to evolve and be tested to ensure they can safely be used universally.

The battle plan

China was able to decode the genetic sequence of COVID-19 and post it publicly by 10th January.  With this blueprint, computer algorithms can be used to design the vaccine. The WHO has launched a multi-country, clinical trial to test four-drug regimens:an experimental anti-viral drug called remdesivir, the antimalarial drug chloroquine (or the related hydroxychloroquine), a combination of two HIV drugs, and those same two HIV drugs along with the anti-inflammatory interferon beta. 

AI to the rescue

An effective weapon brought to bear on COVID-19 is Artificial Intelligence (AI). Companies like Inovio have used the Chinese viral sequence through a machine learning system to generate a DNA based vaccine called INO-4800, now in a preclinical trial.  Moderna Therapeutics also used AI to create a vaccine also under clinical trial. They too used the genetic blueprint posted online to finalise their vaccine mRNA-1273.

Once scientists are able to identify similarities in various viruses and their characteristics, machine learning algorithms can detect correlations in the huge amount of available data, expediting the design of vaccines. Deep learning is also being used to investigate the potential of available anti-viral drugs for use against COVID-19.

The Prognosis

Designing a virus for a deadly enemy like  COVID-19 has to follow the time tested protocols including identifying its genetic structure, designing the vaccine which will not do collateral damage, pre-trial research, animal trials and finally clinical trials on humans. Human clinical trials can often take years. Does mankind have the luxury of this time in the instant case?

Once the danger of COVID-19 had fully revealed itself in January, researchers all over the world had launched clinical trials to test existing medications against the new threat.  So far, the data collected does not give conclusive answers. Some treatments, which have appeared promising in some individual cases, may not work as a universal cure. In fact, the majority of clinical trials fail.

Critically ill volunteer patients are already receiving experimental drugs through the compassionate use programme, which permits hospitals to order such off label drugs in certain cases.  

The good news is that with a huge number of trials ongoing around the world, and billions being spent on them, more and more data is being generated and more important, being shared. 

“We commend the researchers around the world who have come together to systematically evaluate experimental therapeutics,” said Tedros Adhanom, director-general of the World Health Organization (WHO), in a press briefing. “Multiple small trials with different methodologies may not give us the clear, strong evidence we need about which treatments help to save lives.”

Assessments

  • While the biotech companies work relentlessly to find an effective drug and vaccine, governments have to put in place the accepted mantra: surveillance, source tracing, isolation and quarantine to flatten the curve. An integrated national action plan, support by WHO, and global sharing of data and best practices is the immediate need of the time.

  • Prevention remains the most effective measure and simple tools like soap and water can prove to be more effective against the COVID-19 scourge than the best medicines and vaccines.

  • It is preordained that at some point in time, sooner than later, we will have an anti-viral and vaccine for COVID 19. We estimate that it will take anywhere between 8 to 12 months before an effective vaccine is ready for mass use. However, a virus will always remain a threat. Despite the latest vaccines, influenza causes between 12,000 and 60,000 flu deaths each year in the United States. COVID-19 could be equally persistent.