Could oral antivirals be the key to conquering COVID-19?

Woman taking oral antiviral tablet

 

The vulnerabilities of vaccines

There is no doubt that the development of vaccines was a pivotal moment in the COVID-19 pandemic and that they have saved hundreds of thousands of lives globally [1]. However, accessibility issues surrounding the vaccines have highlighted huge inequalities between high- and low-income countries [2, 3]. To achieve global herd immunity, it is estimated that at least 11 billion doses of the vaccine will be needed – the figure required to immunise 70% of the world’s population [2]. At the current rate, approximately 6 billion doses will have been administered by the end of 2021, predominantly in high-income countries [2]. Sadly, it is likely that most people in low-income countries will have to wait another two years before they receive their first dose [3, 4]. This inequitable distribution has allowed the virus to continue to spread and mutate (as with the emergence of the omicron variant in Southern Africa) which, if it continues to do so, could ultimately render the vaccines ineffective [3].

In April 2020, a global initiative known as COVAX was established to enable access to vaccines for all countries, regardless of income. A heavy reliance was placed on the manufacture of COVID-19 vaccines in India; however, the devastating spread of the delta variant of the virus throughout India in April 2021 resulted in a total vaccine export halt due to the huge domestic demand. Bans on vaccine export to meet domestic demand have also occurred in the USA and Europe, further restricting access for low-income countries [3]. In addition, essential components for manufacturing vaccines have been in short supply because of the extraordinary demand, contributing to the issues of accessibility [4].

Antiviral treatment

Historically, developing antiviral drugs to specifically target acute viral infections has been a lengthy process, and often public health measures eradicate the target virus before one can be developed and marketed. An antiviral treatment for COVID-19 was approved in 2020, but as an injectable drug, its use was restricted to hospitalised patients [5].

When someone is infected with COVID-19, the viral load is at its highest around the time of symptom onset. The more unwell a patient becomes, the more the disease is driven by overwhelming systemic inflammation as opposed to viral multiplication, making antivirals virtually redundant at this stage. An antiviral that can be taken orally and prescribed at the onset of symptoms has the best chance of stopping coronavirus in its tracks, before it can spread, and symptoms become severe [5].

The development of an oral antiviral

There are several oral antiviral treatments in the final stages of clinical trials that show promising results as they appear to cut hospitalisations and deaths by up to 89% [6]. In November 2021, The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK granted approval for the first oral antiviral treatment for COVID-19 in the world. It is to be used in patients with mild to moderate COVID-19 symptoms with at least one risk factor for developing severe disease (e.g. obesity, aged >60 years, diabetes or cardiovascular disease) [7–9]. The drug approved by the MHRA mimics the building blocks of virus RNA (its genetic code), called nucleosides. When a virus attempts to replicate its RNA genome to create new copies of itself, the drug is incorporated into the RNA strands, where it has a devastating effect. The drug has the ability to shift its configuration, sometimes mimicking one type of nucleoside (cytidine) and sometimes another (uridine). The insertion of these rogue nucleosides leads to the creation of a faulty blueprint of RNA for the next round of viral genome replication. The eventual result is that the virus suffers insurmountable mutations and dies. This process of non-specific, random nucleoside incorporation means that the drug may well be effective against COVID-19 variants and other coronaviruses [10].

Therefore, this development could not only add to our virus-fighting arsenal here in the UK but may also become a game changer in addressing health inequality globally. Oral medications are inexpensive to produce; they do not require the many components needed to manufacture a vaccine nor do they require cold storage, and they can be taken by the patient at home [11]. The pharmaceutical companies responsible for these breakthrough drugs are already in the process of setting up supply chains and tiered pricing that can be used to support their provision to lower income countries [11].

It has been reiterated many times over the course of the last two years that none of us are safe until we are all safe; perhaps this breakthrough provides the long-awaited key to finally freeing the world of the burden of COVID-19.

The information in this article is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. All content is for general information purposes only. Always seek the guidance of your doctor or other qualified healthcare professional with any questions you may have regarding your health or medical condition.

References

  1. Report: Vaccines saved hundreds of thousands of U.S. lives. Available at: https://www.statista.com/chart/25292/us-lives-saved-by-covid-19-vaccines/. Accessed November 2021.
  2. Nature. COVID vaccines to reach poorest countries in 2023 – despite recent pledges. Available at: https://www.nature.com/articles/d41586-021-01762-w. Accessed November 2021.
  3. UK Parliament: House of Lords Library. Covid-19 vaccinations: Is the global south falling behind? Available at: https://lordslibrary.parliament.uk/covid-19-vaccinations-is-the-global-south-falling-behind/. Accessed November 2021.
  4. Feinmann J. COVID-19: Global vaccine production is a mess and shortages are down to more than just hoarding. BMJ 2021; 375: n2375.
  5. c&en. To conquer COVID-19, create the perfect pill. Available at: https://cen.acs.org/pharmaceuticals/drug-discovery/covid-19-oral-antiviral-pill-candidates/99/i19. Accessed November 2021.
  6. PharmaTimes online. Pfizer’s COVID-19 pill cuts hospitalisation/death risk by 89%. Available at: https://www.pharmatimes.com/news/pfizers_covid-19_pill_cuts_hospitalisationdeath_risk_by_89_1383066. Accessed November 2021.
  7. c&en. Two COVID-19 antiviral pills advance to late-stage trials. Available at: https://cen.acs.org/policy/global-health/Two-COVID-19-antiviral-pills/99/web/2021/09?utm_source=YMAL&utm_medium=YMAL&utm_campaign=CEN&utm_content=pos1. Accessed November 2021.
  8. UK. First oral antiviral for COVID-19, Lagevrio (molnupiravir), approved by MHRA. Available at: https://www.gov.uk/government/news/first-oral-antiviral-for-covid-19-lagevrio-molnupiravir-approved-by-mhra. Accessed November 2021.
  9. The Pharmaceutical Journal. ‘Game-changing’ COVID-19 antiviral drug gets approval in UK for at-risk patients. Available at: https://pharmaceutical-journal.com/article/news/game-changing-covid-19-antiviral-drug-gets-approval-in-uk-for-at-risk-patients. Accessed November 2021.
  10. Nature. How antiviral pill molnupiravir shot ahead in the COVID drug hunt. Available at: https://www.nature.com/articles/d41586-021-02783-1. Accessed November 2021.
  11. Bill & Melinda Gates Foundation. How a new drug for COVID-19 could help improve treatment equity. Available at: https://www.gatesfoundation.org/ideas/articles/molnupiravir-covid-19-drug-access. Accessed November 2021.
  12. Nature. How antiviral pill molnupiravir shot ahead in the COVID drug hunt. Available at: https://www.nature.com/articles/d41586-021-02783-1. Accessed November 2021.

Author: Suzanne Brunt BM

Medical Writer | Porterhouse Medical