O, Soriano-Torres, E, Noa Romero, N L, González Sosa, J M, Enríquez Puertas, A, Fragas Quintero, M, García Montero, D, Martín Alfonso, Y, Infante Hernández, M, Lastre, L, Rodríguez-Pérez, Y, Borrego, V E, González, I G, Vega, R, Ramos Pupo, L M, Reyes, M T, Zumeta Dubé, Amaro, Hernández, I, García de la Rosa, A, Minguez Suárez, L A, Alarcón Camejo, M, Rodríguez, R, Oliva Hernández, C E, Rudd, O, Pérez, and Garcia de la Rosa, Iria/0000-0002-2338-9149
Introduction: Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3.& nbsp;Aims: To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19.& nbsp;Results: Six different concentrations of lithium, ranging 2-12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls.& nbsp;Conclusions: These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19 & PRIME;s patients. The authors are indebted to CICDC staff for their collaborative support and dedication during the experiments. We are grateful to YJ Gonzalez ´ for her technical support, constructive discussions, and scientific input. We also thank J Delgado and SR Paez from Empresa Central de Laboratorios “Jos´e Isaac del Corral”, Havana, Cuba, for their invaluable contribution. We also thank JF Infante for the anatomopathological evaluation of hamsters. CE Rudd is supported by a grant from the Canadian Institutes of Health Research (CIHR).