The Potential Role of Lithium as an Antiviral Agent against SARS-CoV-2 via Membrane Depolarization: Review and Hypothesis

Studies on potential treatments of Coronavirus Disease 2019 (COVID-19) are important to improve the global situation in the face of the pandemic. This review proposes lithium as a potential drug to treat COVID-19. Our hypothesis states that lithium can suppress NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome activity, inhibit cell death, and exhibit immunomodulation via membrane depolarization. Our hypothesis was formulated after finding consistent correlations between these actions and membrane depolarization induced by lithium. Eventually, lithium could serve to mitigate the NLRP3-mediated cytokine storm, which is allegedly reported to be the inciting event of a series of retrogressive events associated with mortality from COVID-19. It could also inhibit cell death and modulate the immune system to attenuate its release, clear the virus from the body, and interrupt the cycle of immune-system dysregulation. Therefore, these effects are presumed to improve the morbidity and mortality of COVID-19 patients. As the numbers of COVID-19 cases and deaths continue to rise exponentially without a clear consensus on potential therapeutic agents, urgent conduction of preclinical and clinical studies to prove the efficacy and safety of lithium is reasonable.