Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19

Despite the availability of vaccines, there remains an urgent need for antiviral drugs with potent activity against SARS-CoV-2, the cause of COVID-19. Millions of people are immune-suppressed and may not be able to mount a fully protective immune response after vaccination. There is also an increasingly critical need for a drug to cover emerging SARS-CoV-2 variants, against which existing vaccines may be less effective. Here, we describe the evolution of molnupiravir (EIDD-2801, MK-4482), a broad-spectrum antiviral agent originally designed for the treatment of Alphavirus infections, into a potential drug for the prevention and treatment of COVID-19. When the pandemic began, molnupiravir was in pre-clinical development for the treatment of seasonal influenza. As COVID-19 spread, the timeline for the development program was moved forward significantly, and focus shifted to treatment of coronavirus infections. Real time consultation with regulatory authorities aided in making the acceleration of the program possible.