Molnupiravir: The First Oral Pill Against COVID-19

Written by: Josephine Chen '24
Edited by: Jason Johnston '23
​​

Molnupiravir is the first oral antiviral drug for COVID-19, and it is highly anticipated to improve the accessibility and efficacy of treatment for patients around the world. 

The coronavirus (COVID-19) is an RNA virus, which means it contains RNA as its genetic material. While DNA consists of two strands of genetic material, RNA only has one strand, which increases the mutation rate and instability of RNA viruses.

Molnupiravir is the first oral antiviral drug for COVID-19, and it is highly anticipated to improve the accessibility and efficacy of treatment for patients around the world. 

The coronavirus (COVID-19) is an RNA virus, which means it contains RNA as its genetic material. While DNA consists of two strands of genetic material, RNA only has one strand, which increases the mutation rate and instability of RNA viruses. The spike proteins on the coronavirus particle allow the virus to attach and enter the body’s cells by binding to the cell’s entry receptors [1]. When inside the cell, the coronavirus is able to replicate their RNA, which allows the virus to spread. 

The coronavirus is abnormally large for an RNA virus with the largest genome of all RNA viruses [2]. Additionally, the coronavirus’ mechanism of infection involves genomic proofreading, which is rarely found in RNA viruses. This mechanism allows the virus to repair any mutations found in its genome when replicating, which is why established antiviral drugs that introduce mutations in the virus do not work effectively against it. While mutations allow some viruses to evolve in the body, the coronavirus utilizes recombination: one strand of the virus can exchange portions of its RNA with other strands of the virus in the body. This machinery creates various versions of the virus, allowing them to infect more cells and even other species [2]. 

Antiviral drugs that are effective against the coronavirus are designed to prevent this proofreading capability of the virus [3]. Molnupiravir can do so by adding “RNA-like building blocks” into the virus’ genome. After the virus replicates with these newly incorporated building blocks, the newly cloned viruses will contain multiple mutations that hinder their ability to function and further infect the body. 

A previous antiviral drug, Remdesivir, had gained much traction when it was first approved by the FDA. However, its efficacy on COVID-19 patients have been a topic of debate recently. Remdesivir, unlike Molnupiravir, avoids the virus’ proofreading capabilities by directly slowing down the replication of the virus [1]. 

One of the main benefits of Molnupiravir is its accessibility. Remdesivir, which is administered intravenously, requires the patient to receive the treatment in a hospital environment. Patients are unable to access the treatment until the illness has progressed so far that the patient must be hospitalized [2]. Furthermore, Remdesivir is only approved for treatment of hospitalized patients. Molnupiravir, on the other hand, can be administered orally in pill form. Without requiring the patient to receive the treatment under hospital supervision, Molnupiravir can be used early on before the illness progresses very much [2]. This is particularly promising for lower-income areas with low vaccination rates.

The effectiveness of Molnupiravir is still being investigated, but the company’s press release cites that the pill has reduced hospitalizations and deaths by 50 percent during the Phase III trial [4]. According to the U.S. Food and Drug Administration (FDA), during phase III of any clinical trial, the study is conducted using anywhere from 300 to 3000 participants who have had the illness. After 29 days of the trial, 7.3% of the patients who received Molnupiravir were hospitalized or died due to the virus. In comparison, 14.1% of patients receiving the placebo were hospitalized or died due to the virus [4]. Additionally, researchers have found that the pill is consistently effective against the different variants of the coronavirus [4]. The Delta, Gamma, and Mu mutations of the virus differ only in their spike proteins, and unlike the COVID-19 vaccines, Molnupiravir’s mechanism does not depend on said proteins.

Although Merck’s data states that there are no serious side effects on the participants in the study, it is important to note that the study excluded many groups: pregnant and breastfeeding woman, persons less than 18 years of age, persons who have received the COVID-19 vaccine prior to the study or plan on receiving the vaccine after the study, and many others [5]. An infectious diseases specialist from Yale Medicine, Dr. Jaimie Meyer, shared her concerns that the drug could have possible side effects on the RNA replication needed for a fetus to develop in the womb, thus leading to birth defects [6]. More research is required to uncover the potential side effects of the pill on these groups of patients. 

Merck has recently submitted a request for an emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA). If this request is accepted, use of Molnupiravir to protect the public from life-threatening situations will be authorized [7]. If the FDA authorization is passed, Merck plans on providing access to the pill to countries around the world, pricing the drug with consideration of the countries’ financial capabilities in midst of the pandemic [4]. 

On November 4, 2021, Britain authorized the use of Molunpiravir, being the first in the world to approve of the oral treatment [8]. Evidently, Molnupiravir has the potential to produce mutations in other RNA viruses beyond the coronavirus [3]. The technology that is being developed during this pandemic can be applied to viral diseases in the future as well. However, despite the promises provided by the pharmaceutical company, more research is needed to expand the scope of patients who can receive Molnupiravir safely. 


Sources:

[1] V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus Biology and replication: Implications for SARS-COV-2 [Internet]. Nature News. Nature Publishing Group; 2020 [cited 2021 Nov 2]. Available from: https://www.nature.com/articles/s41579-020-00468-6 

[2] Cyranoski D. Profile of a killer: The complex biology powering the coronavirus pandemic [Internet]. Nature News. Nature Publishing Group; 2020 [cited 2021 Nov 2]. Available from: https://www.nature.com/articles/d41586-020-01315-7 

[3] Molecular mechanisms of Corona drug candidate molnupiravir unraveled [Internet]. Max-Planck-Gesellschaft. 2021 [cited 2021 Nov 2]. Available from: https://www.mpg.de/17362204/0812-bich-molnupiravir-152115-x

[4] Merck and Ridgeback announce submission of emergency use authorization application to the U.S. FDA for Molnupiravir, an investigational oral antiviral medicine, for the treatment of mild-to-moderate COVID-19 in at risk adults [Internet]. Merck.com. 2021 [cited 2021 Nov 2]. Available from: https://www.merck.com/news/merck-and-ridgeback-announce-submission-of-emergency-use-authorization-application-to-the-u-s-fda-for-molnupiravir-an-investigational-oral-antiviral-medicine-for-the-treatment-of-mild-to-moderate-c/ 

[5] The safety of molnupiravir (EIDD-2801) and its effect on viral shedding of SARS-COV-2 (end-COVID)[Internet]. ClinicalTrials.gov. [cited 2021 Nov 2]. Available from: https://clinicaltrials.gov/ct2/show/NCT04405739 

[6] 9 things you need to know about the new COVID-19 Pill [Internet]. Yale Medicine; 2021 [cited 2021 Nov 2]. Available from: https://www.yalemedicine.org/news/9-things-to-know-about-covid-pill 

[7] Emergency use authorization [Internet]. U.S. Food and Drug Administration. FDA; [cited 2021 Nov 2]. Available from: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization 

[8] Britain authorizes Merck’s molnupiravir, the world’s first approval of oral covid-19 treatment pill. 
Washington Post [Internet]. [cited 2021 Nov 6]; Available from: 
https://www.washingtonpost.com/health/2021/11/04/covid19-pill-merck-molnupiravir-approval-u
k/

​[Image Citation] Aripaka P. Britain approves Merck’s COVID-19 pill in world first. Reuters [Internet]. 
2021 Nov 5 [cited 2021 Nov 6]; Available from: 
https://www.reuters.com/business/healthcare-pharmaceuticals/britain-approves-mercks-oral-covid-19-pill-2021-11-04/