While over a million people worldwide are now confirmed to be infected with COVID-19, we do not yet have an empirical cure or a vaccine for this potentially fatal disease. In this article, Deepak Kumar Sinha, Professor at Institute of Biological Sciences, SAGE University, Indore, discusses some of the approaches being taken by researchers around the world to come up with treatment strategies and vaccines for COVID-19.
A novel acute respiratory infection changed the global perspective of healthcare in December 2019. Humanity is currently facing the challenge of the century — the COVID-19 pandemic. The World Health Organization (WHO) has declared an emergency and governments around the world are devoting a significant amount of attention towards controlling the spread of this disease. The most commonly adopted strategy to contain the disease is a “lockdown” aimed at preventing a chain reaction which can wreak havoc on the medical infrastructure of any country.
In addition to governments, scientists and doctors are at the forefront of the battle against the novel coronavirus. Many researchers and medical professionals are toiling constantly to find a solution to this potentially fatal disease. This article focuses on some recent updates towards the development of new therapeutic strategies and vaccines against COVID-19.
The Novel Coronavirus
Viruses are chemical entities (non-living infectious agents) that need a cell to multiply and survive. SARS-CoV‑2, the virus which causes COVID-19 has single-stranded RNA as its genetic material. Its genome is very small, containing only 15 coding genes and ~30000 nucleotides. In contrast, humans have approximately 30,000 genes and over 3 billion nucleotides in their genome.
Current therapeutic strategies
Currently, the most common treatment strategy is to relieve the patients’ symptoms (which resemble pneumonia), while the hunt remains on to find a complete cure. One approach to devising therapeutic strategies is to unveil the biology of the virus — its structure, how it causes disease (pathogenesis), how it infects people, and how the disease progresses.
SARS-CoV‑2 attacks vital organs such as lungs, heart, intestine and blood vessels. In the lungs, the virus targets cells present in the lining of the lungs (called pneumocytes) and this results in respiratory distress. This, in turn, leads to a decrease in oxygen levels in the blood and finally to death.
A recent preprint report reveals that the virus interferes with heme, an iron-containing compound which is an important component of blood. Another study, also in the preprint stage currently, suggests greater susceptibility of patients with blood group A to SARS-CoV‑2 compared to other blood groups. Additionally, there exists evidence that patients with heart disease and diabetes are more susceptible to this disease. The above study also suggested that certain treatments for both these disorders lead to over-expression of a protein called angiotensin-converting enzyme 2 (ACE2), which SARS-CoV‑2 can bind to and use to access host cells. Hence, this further exacerbates the infection risk for these patients.
A pair of recent studies published in Science provides a clue towards understanding what makes SARS-CoV‑2 so infective. Like all coronaviruses, SARS-CoV‑2 has a spike-like structure on its surface, which gives it an appearance like a crown. These studies suggested that this spike-like structure binds tightly to human cells — much more tightly than the coronavirus that caused the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003.
Apart from understanding the biology of the virus, some drastic steps are needed to restrict the contagion in the current scenario. SARS-CoV‑2, being an RNA virus, can be inhibited by drugs previously used for other RNA viruses, e.g. the Human Immunodeficiency Virus (HIV). Trials are currently underway with a combination of two anti-HIV drugs — lopinavir and ritonavir.
Similarly, the National Institute of Infectious Disease (Japan) demonstrated the use of a drug that was previously developed against the SARS (2003) coronavirus. Additionally, a combination of drugs including chloroquine, a potent medicine used to treat malaria, has also been proposed for clinical usage. It is hypothesized that this combination can prevent the virus from binding to heme. Also in the pipeline are several drugs that are in various phases of clinical trials (Table 1). These include approved compounds such as Kevzara, a rheumatoid arthritis drug that decreases lung complications, successfully tested in COVID-19 patients.
A drug, starting from the time of its inception and research to qualifying all three phases of clinical trials, takes almost 10 to 15 long years to come to the market. Nonetheless, there is a possibility that coordinated international efforts and availability of good funding may make drugs against COVID-19 available within a record time. There is also hope for development of new therapies such as monoclonal antibodies, which may take less time to be available to the doctors due to their speedy trials and their high specificity.
Vaccines stimulate the immune system of an individual to prepare it against a future pathogen attack. This is done by pre-exposing the person to either killed or weakened pathogens, or some of the pathogen’s structural parts, which leads the body to mount a defence response.
For the development of a vaccine against SARS-CoV‑2, a similar approach is under consideration by Serum Institute of India and Sanofi Pasteur, France. An alternative strategy is also to generate antibodies against the spike proteins of the virus, which is being followed by Moderna Inc., MA, USA. Additionally, a German Enterprise, CureVac, aims to design an RNA-based vaccine against the virus. In this approach, RNA that codes for some of the viral proteins is introduced into the body. This RNA can be used to produce viral proteins, against which the body can then synthesize antibodies, thus preparing for the virus’s attack.
All these studies are under different phases of clinical trials (Table 1). These vaccines may become available in the near future, but the time it will take for these to reach the market depends on the efficacy and success in all three phases of clinical trials.
The COVID-19 pandemic has caused an enormous amount of financial and social burden. Research has accelerated, but is still in infancy and will require time and funds to translate into therapies and vaccines. Pandemics like the current outbreak disrupt developing countries that have inadequate financial capabilities or a fragile healthcare system. However, there is hope in the fact that countries across the world have been uniting to fight this challenge. As a citizen, our obligation is to follow official advisories, not believe in myths, and educate ourselves.
Table 1: Some companies currently developing drugs/vaccines against COVID-19CompanyApproachStageStrategyGilead SciencesTreatmentPhase 3RemdesivirAscletis PharmaTreatmentPhase 1Cocktail of Danoprevir and TitonavirModerna TherapeuticsVaccinePhase 1RNA vaccine (mRNA ‑1273)CanSino BiologicsVaccinePhase 1SARS-CoV‑2 genetic code entwined in harmless virusArcturus TherapeuticsVaccinePreclinicalEngineering RNA with nanoparticleBioNTechVaccinePreclinicalmRNACureVacVaccinePreclinicalman-made mRNAEli LillyTreatmentPreclinicalAntibody TreatmentGlaxoSmithkline+ CloverBiopharmaceuticalsVaccinePreclinicalEngineering adjuvants with proteinsInovio PharmaceuticalsVaccinePreclinicalDNA VaccineJohnson & JohnsonVaccine and TreatmentPreclinicalDeactivated virusPfizerVaccine and TreatmentPreclinicalHas not yet revealed strategy, Five-point plan releasedRegeneron PharmaceuticalsTreatmentPreclinicalCocktail of antibodiesSanofiVaccine and TreatmentPreclinicalChimera of RNA viruses, Kevzara drugTakedaTreatmentPreclinicalPlasma of treated patientsVir BiotechnologyTreatmentPreclinicalViral replication inhibitor
Data Derived from: “An updated guide to the coronavirus drugs and vaccines in development” by Damian Garde, STAT News, March 2020
This is a companion discussion topic for the original entry at https://indiabioscience.org/columns/general-science/covid-19-vaccine-development-and-therapeutic-strategies