From Hydroxychloroquine to Ivermectin: what are the anti-viral properties of anti-parasitic drugs to combat SARS-CoV-2?

Background Nearly a year into the COVID-19 pandemic we still lack effective anti SARS-CoV-2 drugs with substantial impact on mortality rates except for dexamethasone. As the search for effective antiviral agents continues, we aimed to review data on the potential of repurposing antiparasitic drugs against viruses in general, with an emphasis on coronaviruses. Methods We performed a review by screening in vitro and in vivo studies that assessed the antiviral activity of several antiparasitic agents: chloroquine, hydroxychloroquine, mefloquine, artesiminins, ivermectin, nitazoxanide, niclosamide, atovaquone, and albendazole. Results For hydroxychloroquine and chloroquine we found ample in vitro evidence of antiviral activity. Cohort studies that assessed the use of hydroxychloroquine for COVID-19 reported conflicting results, but randomized controlled trials (RCTs) demonstrated no effect on mortality rates and no substantial clinical benefits of HCQ (hydroxychloroquine) used either for prevention or treatment of COVID-19. We found two clinical studies of artesiminins and two studies of nitazoxanide for treatment of viruses other than COVID-19, all of which showed mixed results. Ivermectin was evaluated in one RCT and few observational studies, demonstrating conflicting results. As the level of evidence of these data is low, the efficacy of ivermectin against COVID-19 remains to be proven. For chloroquine, hydroxychloroquine, mefloquine, artesiminins, ivermectin, nitazoxanide and niclosamide we found in vitro studies showing some effects against a wide array of viruses. We found no relevant studies for atovaquone and albendazole. Conclusions As the search for an effective drug active against SARS-CoV-2 continues, we argue that pre-clinical research of possible antiviral effects of compounds that could have antiviral activity should be conducted. Clinical studies should be conducted when sufficient in vitro evidence exists, and drugs should be introduced into widespread clinical use only after being rigorously tested in RCTs. Such a search may prove beneficial in this pandemic, or in outbreaks yet to come.