COVID-19 therapeutics development
Updated: Dec 13, 2021
The mask mandate was lifted on July 4, 2021, and despite the immediate feeling of freedom, the number of newly diagnosed COVID-19 patients began to rise . Recently, the rate of rise appears to have achieved stasis in many areas of the country. At this point, prevention of infection is largely relying on an individual’s decision to get vaccinated as well as how well they adhere to the daily habit of face covering and sanitation. Although the delta variant is widely spread and is more transmissible , only one amino acid was mutated in the spike protein of this variant. The Centers for Disease Control and Prevention (CDC) announced that current vaccines should be 80 – 90% effective against most if not all new variants. Patients today have more treatment options against coronavirus disease compared to two years ago. Provided herein is an overview the available treatment options for COVID-19.
Remdesivir is the first and thus far, the only small molecule drug approved by the Food and Drug Administration (FDA) for the treatment of COVID-19. It is developed and sold by Gilead Sciences. The active metabolite of remdesivir is an ATP analog which interferes with the action of viral RNA-dependent RNA polymerase and evades proofreading by viral exoribonuclease, causing a decrease in viral RNA production. Remdesivir was originally tested as an antiviral agent against Ebola and Hepatitis C viruses, but appears to be terminating replication of SARS-CoV-2 RNA more efficiently. The FDA approved emergency authorization use of remdesivir for COVID-19 critically ill patients who need supplemental oxygen. Although WHO halted recommendation of remdesivir due to a lack of sufficient evidence, NIH and FDA still recommend remdesivir as the best treatment of critically ill patients. Further trials are expected.
Dexamethasone is a glucocorticoid steroid medication used to treat rheumatoid arthritis, blood/hormone disorders, allergic reactions, skin diseases, eye problems, breathing problems, bowel disorders, cancer, and immune system disorders. It is also used as a test for an adrenal gland disorder (Cushing's syndrome). In early 2020, some patients developed inflammation in their lungs that could became devastating leading to death. In the UK, among anti-inflammatory drugs, they reported that dexamethasone reduced COVD-19 patients’ death significantly in a clinical trial recruiting over 6,000 patients. For example, deaths were by one-third in patients on ventilators and by one-fifth in patients on oxygen. NIH guidelines recommends only using dexamethasone in patients with COVID-19 who are on a ventilator or supplemental oxygen, since it could harm patients who are at an earlier stage of infection. The British government estimated that the drug has saved a million lives worldwide.
REGEN-COV is an antibody cocktail developed by Regeneron Pharmaceuticals. It consists of two artificial monoclonal antibodies. The mixture of two antibodies bind to the spike protein and prevent mutational escape, producing resistance against SARS-CoV2 virus. REGEN-COV was swiftly focused on after former president Trump claimed that REGEN-COV cured him, although he received a combination of several other therapies as well. REGEN-COV may also act prophylactically. A clinical trial demonstrated a reduction of symptomatic infection by 81% of those who were exposed to the coronavirus within their households.
Interluekin-6 is secreted by immune cells, triggering a cytokine storm. A number of Interleukin-6 inhibitors have proven to treat arthritis and other immune disorders. WHO and NIH recommended two of these drugs sarilumab and tocilizumab for patients with severe or critical COVID-19 infection. Mortality rate was reduced in many cases where these monoclonal antibodies were utilized.
Baricitinib is a drug used to treat rheumatoid arteritis and is a JAK inhibitor which can prevent inflammation. In a large randomized clinical trial, they found that a combination of baricitinib and remdesivir versus remdesivir alone reduced the time of hospitalization by a day. Currently NIH recommends that use of baricitinib when dexamethasone cannot be used for patients with supplemental oxygen.
Favipiravir is an antiviral medication used to treat influenza and was developed by Fuji Film in Japan. Mechanism of action is thought to be related to inhibition of viral RNA-dependent RNA polymerase. Small studies suggested that the drug might clear the coronavirus from the airway in countries including Japan, Korea, Russia, Turkey and India. More rigorous studies are being investigated.
Another drug originally developed in Japan by Dr. Satoshi Ohmura of Kitasato University and Merck in 1970 was ivermectin. This drug is widely used to treat parasite infestations. In humans, this drug was used to treat head lice, scabies, river blindness etc. In veterinary medicine, it is used to prevent heartworm and acariasis. In April 2020, Australian researchers reported that ivermectin blocked replication of SARS-CoV-2 in vitro, however, doses were a lot higher than the maximum tolerant dose for humans. Despite these findings and the admonitions of many governments including Japan, US, and Latin America, the drug has been misused (self-treatment) resulting in hospitalization and in some cases deaths. The most recent warning of FDA stating “You are not a horse. You are not a cow. Seriously. y’all. Stop it.”
Ranging from promising repurposed drugs such as remdesivir to stem cells and other novel therapies, over 2000 clinical trials are under way to treat COVID-19 in U.S. Further investigations are sought to end this historical pandemic.
Written by: Misa S. Anekoji, Ph.D.
Keywords: COVID-19, SARS-CoV2, therapeutics, Remdesivir
NIH COVID-19 treatment guidelines https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/hospitalized-adults--therapeutic-management/
The New York Times Coronavirus Drug and Treatment Tracker
Trends in COVID-19 therapeutic clinical trials, Nature vol. 254, April 2021