556 Abstract. – A novel coronavirus named se- vere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a current outbreak of infection termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 is currently a global pandemic that may cause close to half a billion deaths around the world. Until now, there is no effective treatment for COVID-19. Quinacrine (Qx) has been used since the 1930s as preventive antimalarial compound. It is a recognized small molecule inhibitor of RNA virus replication, with known anti-prion ac- tivity, and identifed as a potent Ebola virus in- hibitor both in vitro and in vivo. Recently, Qx has showed anti-SARS-CoV-2 activity. Herein, we re- view the potential mechanisms associated with quinacrine as an antiviral compound. Key Words: Quinacrine, SARS-CoV-2, COVID-19, Antiviral. Introduction Around the world, the scientifc community is facing a pandemic provoked by a virus from the family Coronaviridae, order Nidovirales and de- nominated SARS-CoV-2 that is the causal agent of COVID-19 pandemic 1,2 . SARS-CoV-2 has a positive-sense single-stranded RNA transmitted mainly from human to human through respira- tory droplets 3-5 . The envelope spike protein of the SARS-CoV-2 can attach the human angio- tensin-converting enzyme II (ACE2) as an entry receptor. ACE2 is expressed in several human tissues including lungs, small intestine, kidneys, heart, thyroid, and adipose tissue 6 . The SARS-CoV-2 infection mainly exhibits fu-like symptoms such as fever, cough, and as- thenia, similar to other coronaviruses 7,8 . It has been reported that high-risk individuals such as elderly subjects or those affected by multimorbid- ities such as hypertension, diabetes mellitus, and cardiovascular disorders, in which the virus pro- duces acute respiratory failure and consequently it can reach to a high death rate 9 . The world faces its worst public health crisis in the modern era, and the disease continues to spread without any effective treatment. Consequently, there is an urgent necessity to fnd effective treatments to reduce its dissemination until successful preven- tion method is developed through vaccination. Currently, there is no existence of any effective treatment against COVID-19 and clinical man- agement is only symptomatic 10 . Actually, the current pharmacological therapy for COVID-19 is focused on drugs with antiviral activ- ity (ribavirin, lopinavir, remdesivir, plasma/immu- noglobulin, chloroquine/hydroxychloroquine), im- munomodulators (interferons and corticosteroids), and supplements (vitamin C, alpha lipoid acid) 11-14 . Herein, we proposed the research of quinacrine, an antimalarial drug with potential antiviral effects along with immunomodulatory properties. Quinacrine Background Quinacrine is an aminoacridine, discovered in the 1920s, that has been used for the treatment of malaria since 1931. It is worth mentioning that its use was empirical during the frst years of World War II. The suppressive antimalarial activity of quinacrine (also known as atabrine or mepacrine) was examined in both Plasmodium vivax and Plasmodium falciparum infections induced by blood inoculation. Quinacrine was 200 times more active than quinine, thus, the oral dose of quinacrine was around one-third of that required of quinine 15 . Quinacrine was also European Review for Medical and Pharmacological Sciences 2021; 25: 556-566 B. PINEDA 1 , V. PÉREZ DE LA CRUZ 2 , R. HERNÁNDEZ PANDO 3 , J. SOTELO 1 1 Laboratorio de Neuroinmunología y Neurooncología, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México 2 Laboratorio de Neurobioquímica y Conducta, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México 3 Unidad de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México Corresponding Author: Benjamin Pineda, MD; e-mail: benpio76@hotmail.com Quinacrine as a potential treatment for COVID-19 virus infection