Molnupiravir and Combination of Nirmatrelvir and Ritonavir (PaxlovidTM) - Oral Anti-viral Drugs in COVID-19: A Systematic Review

The COVID-19 pandemic situation demands the discovery of newer drugs and/ or repurposing of the existing drugs. The anti-viral drugs approved for COVID-19 are remdesivir and favipiravir. Two more directly acting oral anti-viral drugs have been granted Emergency Use Authorization by US-FDA, molnupiravir on December 23, 2021, and nirmatrelvir and ritonavir (PaxlovidTM) on December 22, 2021. Molnupiravir, an RNA-dependent RNA polymerase (RdRp) inhibitor, has also been approved in the UK and is under review with other regulatory agencies. PaxlovidTM (a combination of the new anti-viral drugs nirmatrelvir and ritonavir) has been developed and approved by US-FDA and CDSCO, India. Nirmatrelvir acts by inhibiting 3CL (chymotrypsin-like) protease enzyme and it is combined with ritonavir to slow down its breakdown by cytochrome P450 enzymes and to increase the bioavailability. Both molnupiravir and PaxlovidTM have been approved for mild and moderate COVID-19 and in patients who have a higher risk of disease progression to severe disease including hospitalisation and death. This article systematically reviews the clinical trials of molnupiravir and PaxlovidTM that evaluated their efficacy and safety against COVID-19 in both published and unpublished literature.