Hidroxicloroquina

Hydroxychloroquine accumulation in human organelles also raise their pH, which inhibits antigen processing, prevents the alpha and beta chains of the major histocompatibility complex (MHC) class II from dimerizing, inhibits antigen presentation of the cell, and reduces the inflammatory response.4 Elevated pH in the vesicles may alter the recycling of MHC complexes so that only the high affinity complexes are presented on the cell surface.4 Self peptides bind to MHC complexes with low affinity and so they will be less likely to be presented to autoimmune T cells.4 Hydroxychloroquine also reduces the release of cytokines like interleukin-1 and tumor necrosis factor, possibly through inhibition of Toll-like receptors.4,11

The raised pH in endosomes, prevent virus particles (such as SARS-CoV and SARS-CoV-2) from utilizing their activity for fusion and entry into the cell.8

Hydroxychloroquine inhibits terminal glycosylation of ACE2, the receptor that SARS-CoV and SARS-CoV-2 target for cell entry.9,8 ACE2 that is not in the glycosylated state may less efficiently interact with the SARS-CoV-2 spike protein, further inhibiting viral entry.

Lim HS, Im JS, Cho JY, Bae KS, Klein TA, Yeom JS, Kim TS, Choi JS, Jang IJ, Park JW: Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax. Antimicrob Agents Chemother. 2009 Apr;53(4):1468-75. doi: 10.1128/AAC.00339-08. Epub 2009 Feb 2. 

Furst DE: Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases. Lupus. 1996 Jun;5 Suppl 1:S11-5. 

Collins KP, Jackson KM, Gustafson DL: Hydroxychloroquine: A Physiologically-Based Pharmacokinetic Model in the Context of Cancer-Related Autophagy Modulation. J Pharmacol Exp Ther. 2018 Jun;365(3):447-459. doi: 10.1124/jpet.117.245639. Epub 2018 Feb 8. 

Fox RI: Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum. 1993 Oct;23(2 Suppl 1):82-91. [Article]

Chou AC, Fitch CD: Heme polymerase: modulation by chloroquine treatment of a rodent malaria. Life Sci. 1992;51(26):2073-8. doi: 10.1016/0024-3205(92)90158-l. 

Shippey EA, Wagler VD, Collamer AN: Hydroxychloroquine: An old drug with new relevance. Cleve Clin J Med. 2018 Jun;85(6):459-467. doi: 10.3949/ccjm.85a.17034. 

Devaux CA, Rolain JM, Colson P, Raoult D: New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020 Mar 11:105938. doi: 10.1016/j.ijantimicag.2020.105938. 

Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST: Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005 Aug 22;2:69. doi: 10.1186/1743-422X-2-69. 

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G: Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. 

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20:105949. doi: 10.1016/j.ijantimicag.2020.105949. 

Chary MA, Barbuto AF, Izadmehr S, Hayes BD, Burns MM: COVID-19: Therapeutics and Their Toxicities. J Med Toxicol. 2020 Apr 30. pii: 10.1007/s13181-020-00777-5. doi: 10.1007/s13181-020-00777-5. 

Browning, David J. (2014). Hydroxychloroquine and chloroquine retinopathy. Springer. [ISBN:9781493905973]

FDA Approved Drug Products: Hydroxychloroquine Oral Tablets 

FDA: Emergency use Authorization for Hydroxychloroquine and Chloroquine Revoked