Molnupiravir in Combination with Remdesivir for Severe COVID-19 Patients Admitted to Hospital: a Case Series

Seyed Mohammad Reza  Hashemian; Hamidreza  Jamaati; Farima  Khalili-Pishkhani; Soheil  Roshanzamiri; Raha  Eskandari; Navid  Shafigh; Abbas  Ahmadi; Farzaneh Dastan

doi:10.54034/mic.e1366

Authors

Seyed Mohammad Reza Hashemian Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Hamidreza Jamaati Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Farima Khalili-Pishkhani Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Soheil Roshanzamiri Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0001-8193-5649
Raha Eskandari Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0002-6038-1250
Navid Shafigh Department of Anesthesiology and Critical Care Medicine, School of Medicine, Masih Daneshvari Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0002-1314-296X
Abbas Ahmadi Department of Anesthesiology, School of Medicine, Shahid Beheshti Hospital, Qom University of Medical Sciences, Qom, Iran
Farzaneh Dastan Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0001-7253-4333

DOI:

https://doi.org/10.54034/mic.e1366

Keywords:

SARS-CoV-2, COVID-19, molnupiravir, remdesivir, severe patients, hospitalized

Abstract

Since the start of the COVID-19 pandemic, a large number of trials have examined the efficacy of various medications as potential treatments for COVID-19, but a promising therapeutic option is still missing and under investigation. Molnupiravir is an investigational oral antiviral medication and a nucleoside analogue that suppresses SARS-CoV-2 replication and has been found to be active against common virus variations (including the Delta variant). Several phase 2 and 3 clinical trials have shown high efficacy for direct antiviral activity of molnupiravir as well as its favorable safety and tolerability in mild to moderate Covid-19 patients. The current study was done on five hospitalized, severe COVID-19 patients. It seems that in combination with remdesivir, this novel antiviral could exert a synergistic effect on reducing the severity of symptoms as well as the duration of hospitalization. However, further clinical studies on the use of molnupiravir in the treatment of severe COVID-19 are warranted.

References

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China. N Engl J Med. 2020; 382 (8): 727-733.

WHO Coronavirus (COVID-19) Dashboard. Covid19.who.int. 2022 [cited 16 March 2022]. Available from: https://covid19.who.int/

Mohammadi M, Shayestehpour M, Mirzaei H. The impact of spike mutated variants of SARS-CoV2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines. The Brazilian Journal of Infectious Diseases. 2021;25(4): 101606.

Tabarsi P, Barati S, Jamaati H, Haseli S, Marjani M, Moniri A, et al. Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial. International Immunopharmacology. 2021; 90: 107205.

Zhou S, Hill C, Sarkar S, Tse L, Woodburn B, Schinazi R, et al. β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells. J Infect Dis. 2021; 224 (3): 415-419.

Abdelnabi R, Foo C, De Jonghe S, Maes P, Weynand B, Neyts J. Molnupiravir Inhibits Replication of the Emerging SARS-CoV-2 Variants of Concern in a Hamster Infection Model. J Infect Dis. 2021; 224(5): 749-753.

Cox R, Wolf J, Plemper R. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat Microbiol. 2020; 6(1): 11-18.

Fischer W, Eron J, Holman W, Cohen M, Fang L, Szewczyk L, et al. Molnupiravir, an Oral Antiviral Treatment for COVID-19. 2021. DOI: 10.1101/2021.06.17.21258639.

Hashemian S, Pourhanifeh M, Hamblin M, Shahrzad M, Mirzaei H. RdRp inhibitors and COVID-19: Is molnupiravir a good option?. Biomed Pharmacother. 2022; 146: 112517.

Szemiel A, Merits A, Orton R, MacLean O, Pinto R, Wickenhagen A et al. In vitro selection of Remdesivir resistance suggests evolutionary predictability of SARS-CoV-2. PLOS Pathogens. 2021; 17(9): e1009929.

Gandhi S, Klein J, Robertson A, Peña-Hernández M, Lin M, Roychoudhury P et al. De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report. Nature Communications. 2022; 13(1).

Coronavirus (COVID-19) Update: FDA Authorizes Additional Oral Antiviral for Treatment of COVID-19 in Certain Adults. U.S. Food and Drug Administration. 2022 [cited 5 April 2022]. Available from:

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-oral-antiviral-treatment-covid-19-certain

Kabinger F, Stiller C, Schmitzová J, Dienemann C, Kokic G, S. Hillen H, et al. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nature Structural & Molecular Biology. 2021; 28(9): 740-746.

Abdelnabi R, Foo C, Kaptein S, Zhang X, Do T, Langendries L, et al. The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model. eBioMedicine. 2021; 72: 103595.

Schultz D, Johnson R, Ayyanathan K, Miller J, Whig K, Kamalia B, et al. Pyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2. Nature. 2022. DOI: 10.1038/s41586-022-04482-x.