Author: Suleiman Obeidat, Year 12
The COVID-19 pandemic has been taking over the world the past year. First appearing In Wuhan, China, the virus was quickly able to spread across the globe and cause worldwide panic. As of May 30th 2020, the WHO has reported 5,817,385 confirmed cases and 362 705 deaths deaths globally. Over the past couple months, scientists and pharmaceutical organisations all over the world have been rigorously researching the virus’ mechanisms and possible treatments and vaccines that can help us eradicate the disease.
Structure and Mechanism of the Virus:
Before attempting to develop treatments or vaccines, it is important to deduce the structure and mechanism of the virus causing the COVID-19 disease, called SARS-CoV-2. The virus is a single-strand RNA virus that enters the body by using Spike (S) Proteins on its surface to bind to a receptor in the body called angiotensin-converting enzyme 2 (ACE2) which is found in many cells around the body, primarily type II pneumocytes which are found in the alveoli of the lungs. After binding occurs, the enzyme type II transmembrane serine protease (TMPRSS2) that is present on the surface of the host cell will clear the ACE2 and activate the S proteins. This leads to conformational changes which allows the virus to enter cells. Upon entering the host body cell, SARS-CoV-2 then utilizes an enzyme called RNA-dependent RNA polymerase in order to force the host cell to produce many copies of the mRNA strand found in the virus. The mRNA strands are then translated by the host cell to form the proteins that make up SARS-CoV-2, in order to then produce many copies of the virus which are released from the host cell and infect the body, causing the COVID-19 disease.
Remdesivir:
One of the frontliners in terms of medication to treat COVID-19 is the investigational drug remdesivir, which has been developed by the American biopharmaceutical company Gilead Sciences and has demonstrated efficacy against previous coronaviruses that caused MERS and SARS in 2012 and 2002 respectively. On Friday May 1st the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to use remdesivir in hospitals to treat patients suffering from COVID-19. The FDA stated in the official authorization letter that “it is reasonable to believe that remdesivir may be effective in treating COVID-19” and that “there is no adequate, approved, and available alternative”. The drug is supposed to treat COVID-19 by inhibiting the activity of the RNA-dependent RNA polymerase in SARS-CoV-2, which would hopefully restrict copies of the virus being produced.
Gilead initiated 2 Phase 3 clinical trials to investigate the efficacy and safety of using remdesivir in 5- or 10-day courses to treat around 1600 participants with COVD-19. The trials began on March 15th and Gilead announced on Wednesday April 29th that they found no difference in the efficacy of a 5- or 10-day treatment. Gilead stated that this will “significantly expand the number of patients who could be treated with our current supply of remdesivir”. Also, the National Institute of Allergy and Infectious Diseases (NIAID) initiated an “adaptive, randomized, double-blind, placebo-controlled trial” to investigate the effects of the drug against a placebo and found that “patients who received remdesivir had a 31% faster time to recovery than those who received placebo”. Therefore, these studies tell us 2 important pieces of information; remdesivir speeds up recovery time and it is as effective in 5 days as in 10 days.
A major aspect that has been speculated is the availability and price of remdesivir if it is distributed. The CEO Daniel O’Day revealed In an open letter on April 4th that they have been able to increase their supply to “1.5 million individual doses” which they estimate can be used to provide “well over 140,000 treatment courses for patients.” However, it is important to remember that this is an investigational drug and its true efficacy against COVID-19 on a large scale might be unknown for many months. Furthermore, Gilead hasn’t revealed any information concerning the market and manufacturing price and estimations have been as high as $1000 per course, which causes concern regarding the drug’s availability in poorer countries like Liberia or Sierra Leone. However, despite a company being able to charge for a product under the EUA, Gilead have stated that they are “providing the entirety of this existing supply at no cost, to treat patients with the most severe symptoms of COVID-19. The 1.5 million individual doses are available for compassionate use, expanded access, and clinical trials and will be donated for broader distribution following any potential future regulatory authorizations."
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