Remdesivir: Emergence as a potential cure to pandemic spread (the Concepts)

By Saroj Singh|Updated : May 29th, 2020

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first identified in Wuhan, China in December 2019 and has spread worldwide, resulting in a pandemic. As of May 2020, more than 5.64 million cases were reported across 188 countries resulting in more than 3.52 lakh deaths. More than 2.3 million people recovered.

Remdesivir: Emergence as a potential cure to pandemic spread 

According to the World Health Organization, there are no vaccines available, nor any specific antiviral treatments for COVID-19. However, a drug named remdesivir is designed to obstruct the replication stage of the novel coronavirus SARS-CoV2. 

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What is Remdesivir? 

  • Remdesivir is a broad-spectrum antiviral drug developed by Gilead Sciences, a biopharmaceutical firm. Remdesivir is being tested for COVID-19 treatment and has been authorized for emergency use in the U.S. and approved for use in Japan for people with severe symptoms.
  • It was also approved in the UK in May 2020 but will be rationed because of limited supply. The time it takes to recover from the infection can be shorter.
  • Remdesivir was designed by US-based biotechnology firm Gilead Sciences in 2014 to act against the Ebola virus (which is not a coronavirus).
  • It has since been used for MERS and SERS treatment, both caused by members of the coronavirus family. 
  • Current research is examining whether the antiviral properties of the drug work against SARS-CoV2, the coronavirus that causes the disease COVID-19.
  • Six major trials or studies on remdesivir are underway, including one by WHO. 

How does the Remdesivir Obstruct the novel coronavirus? 

  • The drug remdesivir is designed to obstruct the replication stage of the novel coronavirus SARS-CoV2.
  • The virus creates copies of itself at this stage, which is followed endlessly by the copies creating copies of themselves. Researchers have outlined the exact mechanism of the virus-drug interaction.
  • Once the virus enters the human cell, its genetic material is released which is then copied using the existing mechanism of the body. Various human proteins, viral proteins, and their interactions come into play at every stage of the infection.
  • The key protein in the virus at the replication stage is an enzyme called RdRp which makes copies of the virus by processing the RNA components.
  • Scientifically, an enzyme like this is called polymerase or replicase. In any case, RdRp is the enzyme that is targeted by remdesivir. 

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How it targets the RdRp enzyme? 

  • RdRp processes raw material from the virus RNA to replicate. 
  • When remdesivir is given to a patient, it imitates some of this material, and is incorporated into the replication site. The virus fails to replicate further as remdesivir replace the material that it needs. 

Some new findings on remdesivir action: 

  • With respect to SARS-CoV2, a Chinese research paper has added to the emerging knowledge on remdesivir's action. They imaged the high-resolution SARS-CoV-2 replicase complex structure, with remdesivir bound to it.
  • The structure indicates where the virus RNA template enters the spot for replication. It also shows where the remdesivir is incorporated, and where the replication process is ended.
  • Glied Sciences through a press release confirm that its experimental drug remdesivir, had reduced the time for COVID-19 patients to get better. That is, patients respond to treatment.
  • Patients who received remdesivir showed recovery within 11 days. The drug can help people to survive, who are very ill with the virus. According to a statement from the National Institutes of Health, for those taking remdesivir the mortality rate was 8 percent compared to 11 percent for those in the placebo group. 

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Some Cause of concerns: 

A.Side effect of Remdesivir : 

  • The most common adverse effects of remdesivir include respiratory failure and impairment of organs, including low albumin, low potassium, low red blood cell counts, low number of platelets that help with coagulation, and yellow skin discolouration. Other side effects reported include gastrointestinal distress, elevated blood transaminase levels (liver enzymes), and reactions from the infusion site. 

2.Other possible side effects of remdesivir: 

  • Infusion-related reactions : Infusion-related reactions were seen during  infusion of remdesivir or around the time of administering remdesivir. Signs and symptoms may include: low blood pressure, nausea , vomiting, sweating and shivering.
  • Increases in liver enzyme levels : Increases in liver enzyme levels as seen in abnormal liver blood tests have been seen in people who have received remdesivir, which may be a sign of inflammation or damage to liver cells. 

How India is fighting covid-19 till now : 

a. Remdesivir use in India for Covid-19 patients: 

  • Most doctors are trying ritonavir, lopinavir, and even tocilizumab immuno suppressant, but not remdesivir due to global reports of COVID-19 patients having an adverse reaction of remdesivir.  
  • It is, however a doctor's call whether or not to use the drugs before the results of clinical trials. 

Availability of Remdesivir in India: 

  • Investments have been made since January in ramping up production and establishing a supply chain.
  • It was scaled to 30,000 patients by March end and the company plans to produce enough stock for 1.4 lakh patients by May end.
  • With the exception of pregnant women and children with severe infection, Gilead (the company manufacturing remdesivir) has for now stopped fulfilling individual supply requests under its Compassionate Use programme. 

India will continue to use HCQ 

  • Due to safety concerns, the World Health Organization (WHO) temporarily suspended clinical trials of hydroxychloroquine (HCQ) under its multi-country Solidarity Trial.
  • India has, however, decided to continue using hydroxychloroquine as a prophylactic drug for all frontline workers, including those not in the healthcare sector. 

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Reasons for continuing the use of this drug in India: 

  • The decision by India is based on the country's experience of using HCQ and sufficient data from observational and case-control studies.
  • While this is a new virus whose behaviour is still unclear, it has been known that HCQ works in other coronaviruses. There is some biological validity for its use because it is known to increase the pH of the cell and make it alkaline. Additionally, it blocks the virus entry into the cell.
  • HCQ has minimal and tolerable side effects like nausea, abnormal ECG and occasional palpitations, but the benefits outweigh the risks by far.
  • Additionally, the Solidarity Trial of the WHO used double the dosage prescribed for its patients by ICMR. Given the low dosage in India, the authorities are not extremely concerned about side effects. 

Way Forward: 

  • As researchers have outlined the exact mechanism of the virus-drug interaction. It can be a game-changer as it emerges as a potential cure to Covid -19 pandemic spread.
  • Access to the drug is limited as no one yet knows whether remdesivir is effective in COVID-19 treatment. Also,we can not ignore the fact that limited published information is available on the treatment of COVID-19.
  • Gilead has announced that it has granted non-exclusive voluntary licenses to five generic drug companies to produce remdesivir for distribution in 127 countries.
  • The agreements have been structured so that licensees can set their own prices and do not have to pay royalties to Gilead until the WHO declares an end to the COVID-19 emergency or another medicine or vaccine has been approved for COVID-19.
  • Research and trials are still going on and we must hope something fruitful will come out. The only way to be safe is to take precautions as per WHO's advisory and stay home.

 

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Saroj SinghSaroj SinghMember since Dec 2019
Community Manager [https://www.quora.com/profile/Saroj-Singh-745]
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Rajani Kumari Baodya
Very helpful notes....provide in hindi...🙏

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