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COVID-19 drugs: potential interaction with ATP-binding cassette transporters P-glycoprotein and breast cancer resistance protein



Review


doi: 10.1007/s40005-022-00596-6.


Online ahead of print.

Affiliations

Item in Clipboard

Review

Jaeok Lee et al.


J Pharm Investig.


.

Abstract


Background:

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in acute respiratory distress, fatal systemic manifestations (extrapulmonary as well as pulmonary), and premature mortality among many patients. Therapy for COVID-19 has focused on the treatment of symptoms and of acute inflammation (cytokine storm) and the prevention of viral infection. Although the mechanism of COVID-19 is not fully understood, potential clinical targets have been identified for pharmacological, immunological, and vaccinal approaches.


Area covered:

Pharmacological approaches including drug repositioning have been a priority for initial COVID-19 therapy due to the time-consuming nature of the vaccine development process. COVID-19 drugs have been shown to manage the antiviral infection cycle (cell entry and replication of proteins and genomic RNA) and anti-inflammation. In this review, we evaluated the interaction of current COVID-19 drugs with two ATP-binding cassette transporters [P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)] and potential drug-drug interactions (DDIs) among COVID-19 drugs, especially those associated with P-gp and BCRP efflux transporters.


Expert opinion:

Overall, understanding the pharmacodynamic/pharmacokinetic DDIs of COVID-19 drugs can be useful for pharmacological therapy in COVID-19 patients.


Keywords:

ABC transporters; BCRP; COVID-19; COVID-19 drug; Drug-drug interaction; P-gp.

Conflict of interest statement

Conflict of interestNone of the authors (J Lee, J Kim, J Kang and HJ Lee) have potential conflicts of interest to declare.

Figures



Fig. 1

SARS-CoV-2 infection. a SARS-CoV-2 structure. S-gp, spike glycoprotein; M, membrane protein; E, envelope protein; N, nucleocapsid protein. b Viral infection cycle and molecular interventions are comprised of cell entry, host cell entry by endocytosis or membrane fusion; Replication (of viral proteins and genomic RNA); Assembly; Exocytosis (of mature SARS-CoV-2); Cytokine storm, SARS-CoV-2 infection induces pro-inflammatory pathways (IL-6, TNF, CXCL 10, and cytokines) (Chen et al. 2021a, c). Blue, orange, yellow, and green boxes represent interventions of vaccines, drugs, antibodies, and traditional Chinese medicine plus and vitamins, respectively. CP, convalescent plasma


Fig. 2


Fig. 2

Therapeutic strategies for COVID-19


Fig. 3


Fig. 3

ABC transporters. a P-gp consists of 12 transmembrane domains (TMDs) and 2 nucleotide-binding domains (NBDs) (approximately 150 kDa in size). b BCRP consists of 6 TMDs and 1 NBD as a monomer (approximately 72 kDa). c Drug efflux function of the transporters. ① A drug (substrate/inhibitor [green triangle] of the transporters) permeates into the cell membrane and binds to the affinity site in the TMD of the transporters. ② ATP binds to NBD and then it is hydrolyzed by ATP-hydrolyses. ③ The inward structure of the transporters changes to outward, and transporters efflux the drug to the extracellular region. The green arrows indicate the path of the drug

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