Molecule Information

General Information of the Molecule (ID: Mol02058)

• Name: Gag-Pol polyprotein (POL) ,Human immunodeficiency virus 1
• Synonyms: gag-pol
• Molecule Type: Protein
• Gene Name: gag-pol
• Gene ID: 155348
• Sequence:
  MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQI
  LGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQAAA
  DTGHSSQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGAT
  PQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTT
  STLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRF
  YKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKA
  RVLAEAMSQVTNTATIMMQRGNFRNQRKMVKCFNCGKEGHTARNCRAPRKKGCWKCGKEG
  HQMKDCTERQANFLREDLAFLQGKAREFSSEQTRANSPTISSEQTRANSPTRRELQVWGR
  DNNSPSEAGADRQGTVSFNFPQITLWQRPLVTIKIGGQLKEALLDTGADDTVLEEMSLPG
  RWKPKMIGGIGGFIKVRQYDQILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNFP
  ISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVF
  AIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLD
  EDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFKKQNPDIVIY
  QYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWTV
  QPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAEL
  ELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAH
  TNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPP
  LVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTNKGRQKVVPLTNTTNQKTELQA
  IYLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLAWVPAHKG
  IGGNEQVDKLVSAGIRKILFLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCD
  KCQLKGEAMHGQVDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFL
  LKLAGRWPVKTIHTDNGSNFTSATVKAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKI
  IGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQ
  NFRVYYRDSRNPLWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCV
  ASRQDED
• Function: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.
• Uniprot ID: POL_HV1B1

Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Genus: Lentivirus
Species: Human immunodeficiency virus 1

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

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

Emtricitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Human immunodeficiency virus infection [1]

• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Resistant Drug: Emtricitabine
• Molecule Alteration: Missense mutation+Missense mutation; p.M184V+p.M184I
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Certain amino acid substitutions in the reverse transcriptase of HIV-1 can also reduce susceptibility to emtricitabine (M184V/I) and tenofovir AF (K65R, sometimes plus S68N or L429I; and transiently K70E), although selection of high-level resistance has not occurred with the latter drug over extended periods of culture in vitro.

Zalcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Human immunodeficiency virus infection [2]

• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Resistant Drug: Zalcitabine
• Molecule Alteration: Mutation; .
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Resistance to zalcitabine usually arises from a series of mutations within the HIV pol gene and develops less frequently than resistance to zidovudine.

References

• Ref 1: Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks .Antimicrob Agents Chemother. 2019 Apr 25;63(5):e02533-18. doi: 10.1128/AAC.02533-18. Print 2019 May. 10.1128/AAC.02533-18
• Ref 2: Zalcitabine. An update of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of HIV infection .Drugs. 1997 Jun;53(6):1054-80. doi: 10.2165/00003495-199753060-00009. 10.2165/00003495-199753060-00009