Oral Treatments for COVID-19
There has been a great demand for oral antivirals to treat Covid-19 ever since the monoclonal antibodies and intravenous antiviral therapies appeared in the market. Molnupiravir and Nirmatrelvir-ritonavir were among the earliest candidates for oral treatment of Covid-19 infection. Molnupiravir which acts by competing to bind to the RNA dependent RNA polymerase (RdRP) of SARS CoV-2 virus and induce error in to the viral genome has largely become unpopular because of its lesser efficacy and mutagenic potential which can potentially leave the virus stronger than it was.
Nirmatrelvir-ritonavir has been studied in a phase 2-3 randomised controlled trial and found to reduce the risk of progression to severe Covid-19 among high-risk unvaccinated, non-hospitalised adults. It has further undergone a recent phase 2-3 trial among fully vaccinated individuals with risk factors for severe disease as well as unvaccinated individuals without such risk factors, and found to be not significantly different from placebo.
Simnotrelvir, a protease inhibitor combined with ritonavir is yet another oral drug which has shown efficacy against Covid-19 infection. Ensitrelvir which is also a protease inhibitor is undergoing a clinical trial.
Remdesivir acts by inhibiting viral RdRP but has to be parenterally administered. Mindeudesivir is an oral analogue of Remdesivir which has shown non-inferior efficacy against SARS CoV-2 replication as Nirmatrelvir-ritonavir. Obeldesivir is another remdesivir analogue which is being evaluated in a phase 3 clinical trial.
Notwithstanding the availability of oral treatments, as one may infer from the recent trial of Nirmatrelvir-ritonavir, vaccination should remain sufficient protection against severe Covid-19 among high-risk individuals.