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COVID-19 induces an inflammatory response and, in severe cases, a cytokine storm that can damage the CNS. Antimalarials have unique properties that distinguish them from other anti-inflammatory drugs. (A) They are very lipophilic, which enhances their ability to cross the blood-brain barrier (BBB). Hence, they have the potential to act not only in the periphery but also in the CNS, and could be a useful addition to our limited armamentarium against the SARS-CoV-2 virus. (B) They are non-selective inhibitors of phospholipase A<jats:sub>2<\/jats:sub> isoforms, including cytosolic phospholipase A<jats:sub>2<\/jats:sub> (cPLA<jats:sub>2<\/jats:sub>). The latter is not only activated by cytokines but itself generates arachidonic acid, which is metabolized by cyclooxygenase (COX) to pro-inflammatory eicosanoids. Free radicals are produced in this process, which can lead to oxidative damage to the CNS. There are at least 4 ways that antimalarials could be useful in combating COVID-19. (1) They inhibit PLA<jats:sub>2.<\/jats:sub> (2) They are basic molecules capable of affecting the pH of lysosomes and inhibiting the activity of lysosomal enzymes. (3) They may affect the expression and Fe<jats:sup>2+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> symporter activity of iron transporters such as divalent metal transporter 1 (DMT1), hence reducing iron accumulation in tissues and iron-catalysed free radical formation. (4) They could affect viral replication. The latter may be related to their effect on inhibition of PLA<jats:sub>2<\/jats:sub> isoforms. Inhibition of cPLA<jats:sub>2<\/jats:sub> impairs an early step of coronavirus replication in cell culture. In addition, a secretory PLA<jats:sub>2<\/jats:sub> (sPLA<jats:sub>2<\/jats:sub>) isoform, PLA2G2D, has been shown to be essential for the lethality of SARS-CoV in mice. It is important to take note of what ongoing clinical trials on chloroquine and hydroxychloroquine can eventually tell us about the use of antimalarials and other anti-inflammatory agents, not only for the treatment of COVID-19, but also for neurovascular disorders such as stroke and vascular dementia.<\/jats:p>","DOI":"10.1007\/s12035-020-02093-z","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T05:02:32Z","timestamp":1599541352000},"page":"106-117","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Effects of Antimalarial Drugs on Neuroinflammation-Potential Use for Treatment of COVID-19-Related Neurologic Complications"],"prefix":"10.1007","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9756-7772","authenticated-orcid":false,"given":"Wei-Yi","family":"Ong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Lin","family":"Go","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irwin Kee-Mun","family":"Cheah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Halliwell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,8]]},"reference":[{"key":"2093_CR1","doi-asserted-by":"publisher","unstructured":"Beauverd Y, Adam Y, Assouline B, Samii K (2020) COVID-19 infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose-6-phosphate dehydrogenase deficiency. 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