The novel coronavirus disease 2019 (COVID-19) rapidly spread around the globe. Effective pharmacotherapy is needed to reduce the mortality of COVID-19. Antiviral medications can be a good candidate for the management of COVID-19. Molnupiravir, an antiviral drug, has anti-RNA polymerase activity.

The RNA-dependent RNA polymerase (RdRp) is a key enzyme required for SARS-CoV-2 replication and thus has a pivotal role in the pathophysiology of COVID-19. Molnupiravir (EIDD-2801, MK-4482), targets RdRp. It has been demonstrated to block the SARS-CoV-2 replication in cell lines, animal infected models, and culture media containing airway epithelial cells and thus has been proposed as a potential candidate for the treatment of COVID-19. 

Molnupiravir in COVID-19, a summary of published studies-

Numerous researchers have investigated the inhibitory effects of molnupiravir on COVID-19 replication in animal models.

• Wahl et al. utilized lung-only mice (LoM) to assess lung infection. They administered EIDD-2801, 12–48 h after infection, every 12 h, and observed a significant reduction in the number of viruses in lung tissue 2 days after the start of treatment. They also evaluated the prophylactic effects of molnupiravir by starting it 12 h before infection and found it to be even more effective in the prevention of COVID-19 infection if started earlier. 
• Cox et al. utilized ferrets, which were given EIDD-2801 in a BD dose, 12 and 36 h after infection by oral gavage and found the drug to block the virus transmission 24 h after administration.
• Another study on inhibitory effects of EIDD-2801 on COVID-19 replication utilizing Syrian hamster lung epithelial cells observed a significant reduction in virus replication. 
• Abdelnabi et al. observed a reduction in virus titer and the RNA load of the virus in a dose-dependent manner after being given EIDD-2801. Further, they mentioned that delaying therapy may not stop the virus replication. 
• Abdelnabi et al. also investigated the effect of combination therapy with favipiravir and molnupiravir on the COVID-19 infection. They utilized molnupiravir at 75, 150, 200, and 500 mg/kg doses BID for 4 days, which was initiated 1 h before infection and observed a dose-dependent decrease in virus RNA copies and virus load into lung tissue. Administrating molnupiravir after the first 24 h of COVID-19 infection slowed the progression of COVID-19. Further, administration of high doses of favipiravir (300 and 500 mg/kg) exhibited a reduction in virus load. Additionally, the combination therapy of molnupiravir and favipiravir increased the number of mutations in the RNA structure, further reducing the RNA titer.

 Source- Pharmacology Research and Perspectives, 2022;10(1):e00909. https://doi.org/10.1002/prp2.909