Molnupiravir, an Oral Antiviral Treatment for COVID-19

Fischer, William A.; Eron, Joseph J.; Holman, Wayne; Cohen, Myron S.; Fang, Lei; Szewczyk, Laura J; Sheahan, Timothy P.; Baric, Ralph S.; Mollan, Katie R.; Wolfe, Cameron R.; Duke, Elizabeth R; Azizad, Masoud; BorrotoiEsoda, Katyna; Wohl, David A.; Loftis, Amy James; Alabanza, Paul; Lipansky, Felicia; Painter, Wendy

doi:10.1101/2021.06.17.21258639

Cited by 190 publications

(192 citation statements)

References 23 publications

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…Animal testing trials have also found it to be effective in reducing viral load (18,19). Results from a Phase IIa trial indicated a shorter time to viral RNA clearance and a greater proportion of participants achieving overall clearance with 800 mg of molnupiravir compared to a placebo (20). Molnupilavir was generally well tolerated, with a similar number of adverse events in all groups.…”

Section: Advance Publicationmentioning

confidence: 98%

Update: Drug treatment options for coronavirus disease 2019 (COVID-19)

Shao

2021

BST

View full text Add to dashboard Cite

there were 205 million cumulative diagnoses of coronavirus disease 19 (COVID-19) and 4.3 million deaths worldwide (1). The COVID-19 pandemic has triggered a global health crisis, and effective pharmacological interventions may be the solution to the existing dilemma. The current authors previously proposed three approaches to drug screening for the treatment of COVID-19 (2), and the current article updates the potential treatment options that are currently available (Table 1).The first approach is to standardize existing broadspectrum antivirals that are used to treat other viral infections. Representative drugs are interferon (INF) and ribavirin. In vitro experiments have confirmed that IFN-β effectively blocks the replication of SARS-CoV-2 (3). In a prospective, open-label, randomized, phase II trial in Hong Kong, 86 patients with COVID-19 were given subcutaneous INF β-1b along with lopinavir/ ritonavir and ribavirin within 7 days of symptom onset for 14 days. The time to nucleic acid conversion (7 days verse 12 days) was significantly shorter in patients receiving the triple combination compared to the antiviral control group not receiving interferon (4). In the United Kingdom, a randomized, double-blind, placebocontrolled phase II trial that evaluated the effect of IFN β-1a, known as SNG001, after 14 days of continuous inhalation found a greater likelihood of improvement in patients receiving IFN β-1a than in the placebo group (5). However, another clinical trial of IFN beta-1a given subcutaneously or intravenously found that it did not reduce overall or subgroup mortality in patients with . Therefore, further clinical trials of IFN-β are urgently warranted.The second method is to screen established chemical libraries and to then conduct antiviral trials.Repurposing of older drugs has accelerated the deployment of new therapies for COVID-19. Based on previous experience with the treatment of SARS, Middle East respiratory syndrome, and other novel influenza viruses, numerous large-scale clinical trials have explored various drugs. Two studies have found that mortality and the need for invasive mechanical ventilation are reduced

show abstract

Section: Advance Publicationmentioning

confidence: 98%

Update: Drug treatment options for coronavirus disease 2019 (COVID-19)

Shao

2021

BST

View full text Add to dashboard Cite

show abstract

“…Hence, some other possible RdRp inhibitors are being considered for COVID-19 treatment, which includes molnupiravir, galidesivir, ribavirin, sofosbuvir, and tenofovir [14,15]. Recently molnupiravir, an orally active RdRp inhibitor with a favorable pharmacokinetic profile, has received considerable attention owing to its ability to inhibit SARs-COV-2 replication, its quick clearance of SARs-COV-2, and the accompanying reduction in viral load and fast recovery time [20]. Molnupiravir reaches quantifiable concentration in 0.5 h between 600-1600 mg. Administration of a single dose produces mean C max values up to 13.2 ng/mL and shows median t max between 0.25 and 0.75 h and a biological half-life (t 1/2 ) of 7 h. Its C max and area under the plasma concentration versus time curve (AUC) increases in a dose-proportional manner with no accumulation following multiple doses suggesting that molnupiravir has no accumulative toxicity.…”

Section: Rna-dependent Rna-polymerase (Rdrp)mentioning

confidence: 99%

Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19

Imran

Arora

Asdaq³

et al. 2021

Molecules

154

157

View full text Add to dashboard Cite

The COVID-19 pandemic needs no introduction at present. Only a few treatments are available for this disease, including remdesivir and favipiravir. Accordingly, the pharmaceutical industry is striving to develop new treatments for COVID-19. Molnupiravir, an orally active RdRp inhibitor, is in a phase 3 clinical trial against COVID-19. The objective of this review article is to enlighten the researchers working on COVID-19 about the discovery, recent developments, and patents related to molnupiravir. Molnupiravir was originally developed for the treatment of influenza at Emory University, USA. However, this drug has also demonstrated activity against a variety of viruses, including SARS-CoV-2. Now it is being jointly developed by Emory University, Ridgeback Biotherapeutics, and Merck to treat COVID-19. The published clinical data indicate a good safety profile, tolerability, and oral bioavailability of molnupiravir in humans. The patient-compliant oral dosage form of molnupiravir may hit the market in the first or second quarter of 2022. The patent data of molnupiravir revealed its granted compound patent and process-related patent applications. We also anticipate patent filing related to oral dosage forms, inhalers, and a combination of molnupiravir with marketed drugs like remdesivir, favipiravir, and baricitinib. The current pandemic demands a patient compliant, safe, tolerable, and orally effective COVID-19 treatment. The authors believe that molnupiravir meets these requirements and is a breakthrough COVID-19 treatment.

show abstract

“…Remdesivir (moderately ill patients [10,11], per the metaanalysis of the two trials) Monoclonal antibodies [18][19][20] Molnupiravir [15,16] 25-75% reduction in chance of hospitalisation…”

Section: Role Of the Funding Sourcementioning

confidence: 99%

“…Postulated for Monoclonal antibodies due to effect on viral loads [18][19][20] Possibly Molnupiravir [15,16] Possibly Peginterferon-Lambda [17] 25-75% reduction in duration of infectiousness 25-50%…”

Section: Reduce Duration Of Infectiousnessmentioning

confidence: 99%

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis

Whittaker

Watson

Álvarez-Moreno

et al. 2021

Clinical Infectious Diseases

View full text Add to dashboard Cite

Background The public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods Using a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. Results The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions Advances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

show abstract

Molnupiravir, an Oral Antiviral Treatment for COVID-19

Cited by 190 publications

References 23 publications

Update: Drug treatment options for coronavirus disease 2019 (COVID-19)

Update: Drug treatment options for coronavirus disease 2019 (COVID-19)

Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis

Contact Info

Product

Resources

About