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Chloroquine: Autophagy inhibitor, antimalarial, bitter taste receptor agonist in fight against COVID-19, a reality check

April 22, 2021 - 08:29 -- Open Access
Sharma P, McAlinden KD, Ghavami S, Deshpande DA
Eur J Pharmacol. 2021 Apr 15;897:173928

The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis.

COVID-19 and Syndemic challenges in 'Battling the Big Three': HIV, TB and malaria

March 31, 2021 - 14:20 -- Open Access
Velavan TP, Meyer CG, Esen M, Kremsner PG, Ntoumi F
Int J Infect Dis. 2021 Mar 26:S1201-9712(21)00289-7

Indirect effects of the COVID-19 pandemic have the potential to seriously undermine the health system in sub-Saharan Africa with an increase in the incidences of malaria, tuberculosis (TB) and HIV infections.

NOT Open Access | Antimalarial Quinacrine and Chloroquine Lose Their Activity by Decreasing Cationic Amphiphilic Structure with a Slight Decrease in pH

March 30, 2021 - 14:21 -- NOT Open Access
Kitagawa T, Matsumoto A, Terashima I, Uesono Y
J Med Chem. 2021 Mar 27

Quinacrine (QC) and chloroquine (CQ) have antimicrobial and antiviral activities as well as antimalarial activity, although the mechanisms remain unknown. QC increased the antimicrobial activity against yeast exponentially with a pH-dependent increase in the cationic amphiphilic drug (CAD) structure. CAD-QC localized in the yeast membranes and induced glucose starvation by noncompetitively inhibiting glucose uptake as antipsychotic chlorpromazine (CPZ) did.

NOT Open Access | Does hydroxychloroquine still have any role in the COVID-19 pandemic

March 17, 2021 - 16:58 -- NOT Open Access
Schilling WH, White NJ
Expert Opin Pharmacother. 2021 Mar 16:1-10

The 4-aminoquinolines, chloroquine, and hydroxychloroquine have been used for over 70 years for malaria and rheumatological conditions, respectively. Their broad-spectrum antiviral activity, excellent safety profile, tolerability, low cost, and ready availability made them prime repurposing therapeutic candidates at the beginning of the COVID-19 pandemic.

Pregnancy and COVID-19: Do not overlook malaria

March 17, 2021 - 09:33 -- Open Access
Papaccio M, Castellani R, Zanardini C, Sartori E, Prefumo F, Saccani B.
Int J Gynaecol Obstet. 2021 Mar 13

The synchronous co-infection of malaria and SARS-CoV-2 in pregnancy has recently been reported [1]. A 38-year-old woman born in Burkina Faso, gravida 4 para 3, lived in Italy for 8 years until November 2019 when she returned to Burkina Faso for a short visit.

Applying the CiPA Approach to Evaluate Cardiac Proarrhythmia Risk of some Antimalarials Used Off-label in the First Wave of COVID-19

February 25, 2021 - 09:44 -- Open Access
Delaunois A, Abernathy M, Valentin JP, et al.
Clin Transl Sci. 2021 Feb 23

We applied a set of in silico and in vitro assays, compliant with the CiPA (Comprehensive In Vitro Proarrhythmia Assay) paradigm, to assess the risk of chloroquine or hydroxychloroquine-mediated QT prolongation and Torsades de Pointes (TdP), alone and combined with erythromycin and azithromycin, drugs repurposed during the first wave of COVID-19. Each drug or drug combination was tested in patch clamp assays on 7 cardiac ion channels, in in silico models of human ventricular electrophysiology (Virtual Assay® ) using control (healthy) or high-risk cell populations, and in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes.

Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes

January 26, 2021 - 15:24 -- Open Access
Jordaan P, Dumotier B, Traebert M, Miller PE, Ghetti A, Urban L, Abi-Gerges N
Toxicol Sci. 2021 Jan 23:kfaa194

Substantial efforts have been recently committed to develop COVID-19 medications, and Hydroxychloroquine alone or in combination with Azithromycin has been promoted as a repurposed treatment. While these drugs may increase cardiac toxicity risk, cardiomyocyte mechanisms underlying this risk remain poorly understood in humans. Therefore, we evaluated the pro-arrhythmia risk and inotropic effects of these drugs in the cardiomyocyte contractility-based model of the human heart. We found Hydroxychloroquine to have a low pro-arrhythmia risk, while Chloroquine and Azithromycin were associated with high risk.

ACE2 mutation might explain lower COVID-19 burden in malaria endemic areas

January 26, 2021 - 15:04 -- Open Access
De A, Tiwari A, Dash M, Sinha A
Hum Cell. 2021 Jan 25

The evolving micro-epidemiology of COVID-19 has raised several intriguing concerns including its disproportionately lower burden in malaria–endemic regions. Although there are various explanations cited for this, evolutionary genetic linkages through Angiotensin-Converting Enzyme 2 (ACE2) polymorphisms have been superficially mentioned but not scrutinized further.

Accessing the syndemic of COVID-19 and malaria intervention in Africa

January 16, 2021 - 09:39 -- Open Access
Shi B, Zheng J, Xia S, Lin S, Wang X, Liu Y, Zhou XN, Liu J
Infect Dis Poverty. 2021 Jan 7;10(1):5

The pandemic of the coronavirus disease 2019 (COVID-19) has caused substantial disruptions to health services in the low and middle-income countries with a high burden of other diseases, such as malaria in sub-Saharan Africa. The aim of this study is to assess the impact of COVID-19 pandemic on malaria transmission potential in malaria-endemic countries in Africa.

Tuberculosis and malaria in the age of COVID-19

January 5, 2021 - 15:07 -- Open Access
The Lancet Infectious Diseases
Lancet Infect Dis. 2021 Jan;21(1):1

With the world still focused on the COVID-19 pandemic and hopes for vaccine rollout, the 2020 WHO global reports on tuberculosis and malaria are timely reminders that these diseases remain two of the three deadliest infectious diseases.


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