Molecule Information

General Information of the Molecule (ID: Mol01013)

• Name: Multidrug resistance protein 1 (ABCB1) ,Plasmodium vivax
• Synonyms: MDR1; Multidrug resistant protein 1; Fragment
• Molecule Type: Protein
• Gene Name: MDR1
• Sequence:
  DEVEKELNKKGTFELYKKIKTQKIPFFLPFKCLPSSHRKLLGVSFVCATISGGTLPFFVS
  VFGVIMKNMNLGENVNDIIFSLVLIGIFQFILSFISSFCMDVVTTKILKTLKIEFLKSVF
  YQDGQFHDNNPGSKLTSDLDFYLEQVNAGIGTKFITIFTYASAFLGLYIWSLFKNARLTL
  CITCVFPLIYICGVICNKKVKINKKTSLLYNNNTMSIIEEALVGIRTVVSYCGENTILKK
  FNLSEKLYSKYTLKANLMESLHIGMINGFILASYAFGFWYGTRIIISDLSNQQPNNDFHG
  GSVISILLGVLISMFMLTIILPNITEYMKSLEATNNLYEIINRKPLVENNQDGKKLKDIK
  KIQFKNVRFHYDTRKDVEIYKDLNFTLTEGKTYAFVGESGCGKSTILKLIERLYDPTEGD
  VIINDSHNLKDVNLKWWRSKIGVVSQDPLLFSNSIKNNIKYSLYSLKDLEALSEESNEDG
  FSSQSDSNSRNSCRAKCAGDLNDMIQTTDSTELIQVRKNYETIEDSEVVSVSKKVLIHDF
  VSALPDKYETLVGSNASKLSGGQKQRISIARAIIRNPKILILDEATSSLDNKSEYLVQKT
  INNLKGNENRITIIIAHRLSTIRYANTIFVLSNRENGSTVDVDVLGEDPTKDSNEKNEKH
  DKQEKGGKNSSANQKIGNAGSYIIEQGTHDALMKNKNGIYYTMINNQKVSSKSSSNNDND
  KDSDMKSSIYKDSERGYDPDEANGNAKNESASAKKSEKMSDAKASNTNAGGRLAFLRNLF
  KRKPKAPNNLRVVYREIFSYKKDIAIIALSIMVAGGLYPLFALFYAKYVGTLFDFANLEA
  NSNKYSLYILVIAIAMFISETLKNYYNNVIGEKVEKTMKLRLFENILYQEISFFDQDSHA
  PGLLSAHINRDVHLLKTGLVNNIVIFTHFIVLFLVSMVMSFYFCPIVAAVLTGTYFIFMR
  VFAIRARIAANKDVEKKRVNQPGTAFVYNSDDEIFKDPSFLIQEAFYNMNTVIIYGLEDY
  FCTLIEKAIDYSNKGQKRKTLINSMLWGFSQSAQLFINSFAYWFGSFLIRRGTIQVDDFM
  KSLFTFLFTGSYAGKLMSLKGDSENAKLSFERYYPLITRKSLIDVRDNGGIKIKNSNDIK
  GKIEIMDVNFRYLSRPNVPIYKDLTFSCESKKTTAIVGETGSGKSTVMSLLMRFYDLKND
  HHIVFKNEQTGESSKEQMQQGDEEQNVGMKNANEFSSSKEGADGQSSTLFKNSGKILLDG
  VDICDYNLKDLRNLFSIVSQEPMLFNMSIYENIKFGKENATREDVKRACKFAAIDEFIES
  LPNQYDTNVGPYGKSLSGGQKQRIAIARALLREPKILLLDEATSSLDSNSEKLIEKTIVD
  IKDKADKTIITIAHRIASIKRSDKIVVFNNPDRTGSFVQAQ
• Uniprot ID: A0A1V0PL80_PLAVI

Kingdom: N.A.
Phylum: Apicomplexa
Class: Aconoidasida
Order: Haemosporida
Family: Plasmodiidae
Genus: Plasmodium
Species: Plasmodium vivax

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Chloroquine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Malaria [1]

• Resistant Disease: Malaria [ICD-11: 1F45.0]
• Resistant Drug: Chloroquine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Plasmodium vivax strains; 5855
• Mechanism Description: Patients with CQ-resistant P. vivax parasites presented a higher gene expression of pvcrt-o and pvmdr-1 at D0 and DR when compared to the susceptible group. For the CQR patients, median gene expression values at D0 and DR, presented 2.4 fold (95% CI: 0.96-7.1) and 6.1 fold (95% CI: 3.8-14.3) increase in pvcrt-o levels compared to the susceptible patients at D0 with 0.12 fold (95% CI: 0.034-0.324). Median gene expression for pvmdr-1 presented 2.0 fold (95% CI: 0.95-3.8) and 2.4 fold (95% CI: 0.53-9.1) increase levels at D0 and DR, for the CQR patients versus 0.288 fold (95% CI: 0.068-0.497) for the susceptible patients.

Disease Class: Malaria [2]

• Resistant Disease: Malaria [ICD-11: 1F45.0]
• Resistant Drug: Chloroquine
• Molecule Alteration: Missense mutation; p.976F
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Plasmodium vivax isolates; 5855
• Mechanism Description: In Southeast Asia the pvmdr1 976 F allele has been associated with reduced susceptibility to CQ. Finding the pvmdr1 976 F allele in 7/41 (17%) P. vivax might thus indicate a degree of CQ tolerance but probably not resistance in Honduras.

Quinine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Malaria [3]

• Resistant Disease: Malaria [ICD-11: 1F45.0]
• Resistant Drug: Quinine
• Molecule Alteration: Missense mutation; p.M908L
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Plasmodium vivax isolates; 5855
• Experiment for Molecule Alteration: In vitro drug assay
• Experiment for Drug Resistance: Analysis of genetic polymorphisms assay
• Mechanism Description: The pvmdr1 M908L substitutions in pvmdr1 in our samples was associated with reduced sensitivity to chloroquine, mefloquine, pyronaridine, piperaquine, quinine, artesunate and dihydroartem.

Investigative Drug(s) 1 drug(s) in total

Dihydroartemisinin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Malaria [3]

• Resistant Disease: Malaria [ICD-11: 1F45.0]
• Resistant Drug: Dihydroartemisinin
• Molecule Alteration: Missense mutation; p.M908L
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Plasmodium vivax isolates; 5855
• Experiment for Drug Resistance: In vitro drug assay
• Mechanism Description: Studies of genetic polymorphisms in two candidate genes of drug resistance (pvmdr1 and pvcrt-o) of the P. vivax isolates from this area and found association between the M908L substitution in pvmdr1 with reduced sensitivities to and chloroquine, mefloquine, pyronaridine, piperaquine, quinine, artesunate and dihydroartem.

References

• Ref 1: Expression levels of pvcrt-o and pvmdr-1 are associated with chloroquine resistance and severe Plasmodium vivax malaria in patients of the Brazilian Amazon. PLoS One. 2014 Aug 26;9(8):e105922. doi: 10.1371/journal.pone.0105922. eCollection 2014.
• Ref 2: Drug resistance associated genetic polymorphisms in Plasmodium falciparum and Plasmodium vivax collected in Honduras, Central America. Malar J. 2011 Dec 19;10:376. doi: 10.1186/1475-2875-10-376.
• Ref 3: Ex vivo susceptibilities of Plasmodium vivax isolates from the China-Myanmar border to antimalarial drugs and association with polymorphisms in Pvmdr1 and Pvcrt-o genes. PLoS Negl Trop Dis. 2020 Jun 12;14(6):e0008255. doi: 10.1371/journal.pntd.0008255. eCollection 2020 Jun.