Molnupiravir

Molnupiravir (MK-4482/EIDD-2801) is an oral, mutagenic, anti-viral compound. EIDD-2801 was invented at Drug Innovations at Emory (DRIVE), LLC, a not-for-profit biotechnology company wholly owned by Emory University, to treat against equine encephalitis and influenza.

The rights were bought by Ridgeback Biotherapeutics on March 19, 2020. After failing to receive any further government grants, Ridgeback signed a collaboration agreement to develop the compound with Merck (a.k.a. MSD [Merck Sharp & Dohme]), which was announced on May 26, 2020.

• Malone & Campbell (Sep 13, 2021) in Nature. Title: Molnupiravir: coding for catastrophe
  • Molnupiravir works by inserting catastrophic errors into the genome of the virus. “Molnupiravir, a wide-spectrum antiviral that is currently in phase 2/3 clinical trials for the treatment of COVID-19, is proposed to inhibit viral replication by a mechanism known as ‘lethal mutagenesis’. Two recently published studies reveal the biochemical and structural bases of how molnupiravir disrupts the fidelity of SARS-CoV-2 genome replication and prevents viral propagation by fostering error accumulation in a process referred to as ‘error catastrophe’.”

Seems…scary?

A paper authored by Kristian Thorlund, Kyle Sheldrick, Gideon Meyerowitz-Katz, Sonal Singh, and Andrew Hill critiqued the MOVe-OUT clinical trial.¹⁾

In October 2021, Merck and Ridgeback Biotherapeutics reported that data from their Phase 3 clinical trial showed molnupiravir “cuts the risk of hospitalization and death from COVID-19 by 50% in people who have mild to moderate forms of the disease.”^{2) 3)}

• December 13, 2021 (NYT) Merch's COVID pill might post risks for pregnant women
  • “Some laboratory studies suggest that molnupiravir can insert errors in DNA, which could in theory harm a developing fetus, sperm cells or children.”
• December ?, 2021 (leadpatriot.com) NYT Quietly Reported That Miracle Covid Drug Can Mutate DNA, Cause Birth Defects And Male Infertility
  • Researchers studying this drug included some from the University of North Carolina, including Ronald Swanson, which happens to be where Ralph Baric works.

The following is an ongoing list of countries that have purchased doses of molnupiravir, sorted by date.

A June 25, 2020 Washington Post article by Christopher Rowland ponders the ethics of the strategy “flipping” small molecules by the small, private company Ridgeback Biotherapeutics, who purchased the rights to license molnupiravir for an undisclosed sum after it was developed with federal funds. Then two months later, they ink a deal with Merk. Ridgeback Biotherapeutics is poised to profit handsomely selling the oral pill around the globe to reduce hospitalizations and deaths during the pandemic.

Former BARDA immunologist Rick Bright's whistleblower complaint argues that federal officials inappropriately tried to steer U.S. money to an unproven treatment for the covid pandemic.

It has shown broad spectrum anti-viral properties against respiratory syncytial virus, influenza, chikungunya, Ebola, Venezuelan equine encephalitis virus, and Eastern equine encephalitis viruses.

The development of EIDD-2801 has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), under contract numbers HHSN272201500008C and 75N93019C00058, and from the Defense Threat Reduction Agency DTRA, under contract numbers HDTRA1-13-C-0072 and HDTRA1-15-C-0075.

EIDD-2801 was first patented in 2018. (notable George R. Painter is one of the inventors listed on the patent.)

In testing with collaborators at the University of North Carolina at Chapel Hill and Vanderbilt University Medical Center, the active form of EIDD-2801, which is called EIDD-1931, has shown efficacy against the related coronaviruses SARS (Severe Acute Respiratory Syndrome)- and MERS-CoV. It is noteworthy that Ralph Baric is a contributing author in the Journal of Virology paper regarding EIDD-1931.

Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets

Webcast presentation by Wendy Painter "REDUCTION IN INFECTIOUS SARS-CoV-2 IN TREATMENT STUDY OF COVID-19 WITH MOLNUPIRAVIR"

An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice

Molnupiravir promotes SARS-CoV-2 mutagenesis via the RNA template

NCT04746183 AGILE (Early Phase Platform Trial for COVID-19) is a multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II Bayesian randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19.

NCT04392219 - Phase I Clinical Trial managed by Covance Leeds Clinical Research Unit in Leeds, United Kingdom

NCT04405739 END-COVID is a phase II multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of EIDD-2801 on SARS-CoV-2 Virus Shedding in Newly Hospitalized Adults with polymerase chain reaction (PCR)-Confirmed COVID-19.

NCT04405570 is a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare the safety, tolerability, and antiviral activity of EIDD-2801 versus placebo as measured by infectious virus detection in symptomatic adult outpatients with COVID-19.

NCT04575597 is a Phase 2/3 Clinical Trial to Study the Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19.

NCT04575584 is a phase 2/3 clinical trial to efficacy and safety of molnupiravir (MK-4482) in hospitalized adult participants with COVID-19.

A Phase III Clinical Trial was registered to determine the safety and efficacy of molunupiravir for post-exposure prophylaxis of Covid-19. Merk has an overview of their MOVe-AHEAD Trial on their website. Merk issued a press release with the interim results of their phase III trial.The results of the Phase III clinical trial were published in the NEJM on December 16, 2021.

On November 4, 2021, the UK Medicines and Healthcare products Regulatory Agency granted authorization in the United Kingdom for molnupiravir (with marketing/trade name Lagevrio) for mild to moderate cases of Covid-19.

On December 23, 2021, the USA FDA issued an emergency use authorization (EUA) for molnupiravir for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19. Based on findings from animal reproduction studies, molnupiravir may cause fetal harm when administered to pregnant individuals.

Phase III Clinical Trial in India

Bangladeshi drugmaker, Beximco Pharmaceuticals, manufactured and sold the world's first generic version of Merck's COVID-19 pill, molnupiravir, called Emorivir. The medicine is reported to have a maximum retail price of 70 taka (82 cents) per capsule, or 2,800 taka ($33) for a full course.

On November 30, 2021, the US FDA Antimicrobial Drugs Advisory Committee Voted 13-10 in favor of Molnupiravir for Treatment of Mild to Moderate COVID-19 in High Risk Adults. An article in Pharmacy Practice News provides a summary of the meeting. A youtube recording is available here. Presentation materials are available here.

After being rejected for publication in medical journals, a correspondence was posted on an online forum Virological.org that warns about sub-lethal mutagenesis when using molnupiravir for Covid-19.

Supercharging New Viral Variants: The Dangers Of Molnupiravir (Part 1)