Related Experiment Video

Updated: Dec 4, 2025

High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity
09:09

High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity

Published on: November 16, 2016

8.2K

System biological investigations of hydroxychloroquine and azithromycin targets and their implications in QT interval

Abdul Arif Khan1, Zakir Khan2

  • 1Indian Council of Medical Research-National AIDS Research Institute, Pune, Maharashtra, 411026, India.

Chemico-Biological Interactions
|October 25, 2020
PubMed

Insights

Hydroxychloroquine and Azithromycin combination may prolong QT interval. Computational analysis identified HSP90AA1 and AKT1 as key drug targets, suggesting PI3K/Akt, VEGF, and ERBB2 pathways are involved in this adverse event.

Area of Science:

  • Pharmacology
  • Computational Biology
  • Cardiology

Background:

  • The COVID-19 pandemic lacks a definitive treatment, leading to drug repurposing efforts.
  • Hydroxychloroquine (HCQ) and Azithromycin (AZM) combination is a widely discussed therapeutic option.
  • QT interval prolongation is a significant adverse event associated with HCQ and AZM.

Purpose of the Study:

  • To investigate the drug interactions between HCQ and AZM.
  • To identify molecular targets and pathways contributing to QT interval prolongation caused by this drug combination.
  • To provide a computational basis for understanding and mitigating HCQ-AZM associated cardiotoxicity.

Main Methods:

  • System biological investigation of HCQ and AZM targets.
  • Screening of key proteins and pathways involved in QT interval prolongation.
  • Identification of core hub protein drug targets using node degree value.

Main Results:

  • HSP90AA1 was identified as a key target exclusively associated with HCQ.
  • AKT1 was identified as a key target exclusively associated with AZM.
  • PI3K/Akt, VEGF, and ERBB2 pathways were highlighted as crucial for understanding the role of HCQ and AZM in QT interval prolongation.

Conclusions:

  • Computational findings suggest specific protein targets (HSP90AA1, AKT1) and pathways (PI3K/Akt, VEGF, ERBB2) linked to HCQ-AZM induced QT prolongation.
  • These identified targets and pathways offer potential strategies for reducing the risk of cardiotoxicity.
  • Experimental validation is recommended to confirm these computational predictions and draw definitive conclusions.
Keywords:
Adverse reactionsCOVID-19Cardiac arrhythmiaDrug targetsNetwork pharmacology

More Related Videos

Zebra II as A Novel System to Record Electrophysiological Signals in Zebrafish06:15

Zebra II as A Novel System to Record Electrophysiological Signals in Zebrafish

Published on: August 16, 2024

664
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.2K

Related Concept Videos

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
1.6K
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response01:15

Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response

Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
241
Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
158
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
2.4K
Antihypertensive Drugs: Thiazide-Class Diuretics01:15

Antihypertensive Drugs: Thiazide-Class Diuretics

Thiazide diuretics are sulfonamide derivatives featuring a benzothiadiazine ring system in their molecular structure. Based on this structure, thiazide diuretics can be categorized into two groups: thiazide-type and thiazide-like diuretics. Thiazide-type diuretics, including hydrochlorothiazide and chlorothiazide, consist of a benzothiadiazine backbone with an attached sulfonamide group. Thiazide-like diuretics, such as chlorthalidone and indapamide, lack the thiazide ring but demonstrate...
1.4K
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers01:20

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
1.3K