The antiviral agents against COVID-19 mostly interfere with viral functions or host proteins. Most of the investigational antiviral drugs for the treatment of COVID-19 patients were indicated for other conditions and now are being repurposed for their probable activity against SARS-CoV-2. Some of the potential antivirals currently under investigation have shown promising against COVID-19.

Nitric oxide (NO) is an available, cheap, and well-tolerated antiviral with adequate evidence for its therapeutic and prophylactic effects. Patients with mild to severe COVID-19 and ARDS have been shown to benefit from NO treatment. Further, it also reduces respiratory effort and oxygen requirement in patients receiving oxygen supplementation and prevents COVID-19 progression in infected patients. Its common adverse effects are Methemoglobinemia and the production of nitric dioxide (a byproduct of NO with a safety limit of 2 ppm) which should be viewed while determining the proper dose. Evidence suggests the minimum effective dose of NO in the treatment of bacterial pneumonia to be 160 ppm, where no adverse effect was observed. Numerous trials are evaluating NO at various dosages and in patients with different levels of severity of COVID-19.

Molnupiravir has shown its effectiveness by reducing the duration of infection in patients with COVID-19 and preventing inter-individual viral transmission. Thus, it can be utilized in individuals for whom a vaccine is not available or who are unwilling to be vaccinated. molnupiravir has been described as safe, with a few mild or moderate adverse effects such as diarrhea and headache. 

Plitidepsin has demonstrated in vivo and ex vivo antiviral effects against SARS-CoV-2 and is nearly 27-fold more potent than remdesivir. It prevents viral resistance as it affects a host protein instead of a viral target.

Arbidol remains the agent with the most controversial results regarding COVID-19 patients. It has not demonstrated good efficacy in patients with severe COVID-19 and the clinical outcomes of treatment with arbidol depend on disease severity. Thus more RCTs with large sample sizes are warranted to evaluate the effectiveness of arbidol in patients with COVID-19. A study that compared the effectiveness of arbidol and lopinavir/ritonavir showed that arbidol could significantly decrease the mortality rate.

Thus the current evidence predicts molnupiravir, plitidepsin, and NO to play a major role in the treatment of COVID-19 soon. More RCTs are warranted to evaluate the safety and efficacy of repurposed investigational antivirals for the treatment of COVID-19.

Source- Arch Virol, 2022. https://doi.org/10.1007/s00705-022-05368-z