Repurposing Quinoline and Artemisinin Antimalarials as Therapeutics for SARS-CoV-2: Rationale and Implications

[Image: see text] The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 116 million individuals globally and resulted in over 2.5 million deaths since the first report in December 2019. For most of this time, healthcare professionals have had few tools at their disposal. In December 2020, several vaccines that were shown to be highly effective have been granted emergency use authorization (EUA). Despite these remarkable breakthroughs, challenges include vaccine roll-out and implementation, in addition to deeply entrenched antivaccination viewpoints. While vaccines will prevent disease occurrence, infected individuals still need treatment options, and repurposing drugs circumvents the lengthy and costly process of drug development. SARS-CoV-2, like many other enveloped viruses, require the action of host proteases for entry. In addition, this novel virus employs a unique method of cell exit of deacidified lysosomes and exocytosis. Thus, inhibitors of lysosomes or other players in this pathway are good candidates to target SARS-CoV-2. Chemical compounds in the quinoline class are known to be lysomotropic and perturb pH levels. A large number of quinolines are FDA-approved for treatment of inflammatory diseases and antimalarials. Artemisinins are another class of drugs that have been demonstrated to be safe for use in humans and are widely utilized as antimalarials. In this Review, we discuss the use of antimalarial drugs in the class of quinolines and artemisinins, which have been shown to be effective against SARS-CoV-2 in vitro and in vivo, and provide a rationale in employing quinolines as treatment of SARS-CoV-2 in clinical settings.