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Reverse-transcriptase inhibitor

Source πŸ“

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Mutations in response to NNRTIs decrease the binding of the drug to this pocket. Treatment with a regimen including efavirenz (EFV) and nevirapine (NVP) typically results in mutations L100I, Y181C/I, K103N, V106A/M, V108I, Y188C/H/L and G190A/S. There are three main mechanisms of NNRTI resistance. In the first NRTI mutations disrupt specific contacts between the inhibitor and the NNRTI binding pocket. An example of this is K103N and K101E which sit at the entrance of the pocket, blocking the entrance/binding of the drug. A second mechanism is the disruption of important interactions on the inside of the pocket. For example, Y181C and Y188L result in the loss of important aromatic rings involved in NNRTI binding. The third type of mutations result in changes in the overall conformation or the size of the NNRTI binding pocket. An example is G190E, which creates a steric bulk in the pocket, leaving little or no room for an NNRTI to tightly bind.
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the drug . A prime example for this mechanism is the M184V mutation that confers resistance to lamivudine (3TC) and emtricitabine (FTC). Another well characterized set of mutations is the Q151M complex found in multi-drug resistant HIV which decreases reverse transcriptase's efficiency at incorporating NRTIs, but does not affect natural nucleotide incorporation. The complex includes Q151M mutation along with A62V, V75I, F77L, and F116Y. A virus with Q151M alone is intermediately resistant to zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), and slightly resistant to abacavir (ABC). A virus with Q151M complexed with the other four mutations becomes highly resistant to the above drugs, and is additionally resistant to lamivudine (3TC) and emtricitabine (FTC).
518:. This is a reverse of the polymerase reaction in which the pyrophosphate/PPI released during nucleotide incorporation reacts with the incorporated drug (monophosphate) resulting in the release of the triphosphate drug. This 'unblocks' the DNA chain, allowing it to be extended, and replication to continue. Excision enhancement mutations, typically M41L, D67N, K70R, L210W, T215Y/F, and K219E/Q, are selected for by thymidine analogs AZT and D4T; and are therefore called thymidine analog mutations (TAMs). Other mutations including insertions and deletions in the background of the above mutations also confer resistance via enhanced excision. 502:
mutations in reverse transcriptase that make the virus less susceptible to NRTIs and NNRTIs. Aspartate residues 110, 185, and 186 in the reverse transcriptase polymerase domain are important in the binding and incorporation of nucleotides. The side chains of residues K65, R72, and Q151 interact with the next incoming nucleotide. Also important is L74, which interacts with the template strand to position it for base pairing with the nucleotide. Mutation of these key amino acids results in reduced incorporation of the analogs.
320:, also known as TDF is a so-called 'prodrug' with the active compound deactivated by a molecular side chain that dissolves in the human body allowing a low dose of tenofovir to reach the site of desired activity. One example of the prodrug form is tenofovir disoproxil fumarate with the trade name Viread (Gilead Sciences Inc USA). It is approved in the US for the treatment of both HIV and hepatitis B. 85:. The viral DNA is then integrated into the host chromosomal DNA, which then allows host cellular processes, such as transcription and translation, to reproduce the virus. RTIs block reverse transcriptase's enzymatic function and prevent completion of synthesis of the double-stranded viral DNA, thus preventing HIV from multiplying. 510:
There are two major mechanisms of NRTI resistance. The first being reduced incorporation of the nucleotide analog into DNA over the normal nucleotide. This results from mutations in the N-terminal polymerase domain of the reverse transcriptase that reduce the enzyme's affinity or ability to bind to
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In contrast, NNRTIs have a completely different mode of action. NNRTIs block reverse transcriptase by binding directly to the enzyme. NNRTIs are not incorporated into the viral DNA like NRTIs, but instead inhibit the movement of protein domains of reverse transcriptase that are needed to carry out
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A similar process occurs with other types of viruses. The hepatitis B virus, for example, carries its genetic material in the form of DNA, and employs an RNA-dependent DNA polymerase to replicate. Some of the same compounds used as RTIs can also block HBV replication; when used in this way they are
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Hsiou, Y; Das, K; Ding, J; Clark Jr, AD; Kleim, JP; RΓΆsner, M; Winkler, I; Riess, G; et al. (1998). "Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug
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While NRTIs and NNRTIs alike are effective at terminating DNA synthesis and HIV replication, HIV can and eventually does develop mechanisms that confer the virus resistance to the drugs. HIV-1 RT does not have proof-reading activity. This, combined with selective pressure from the drug, leads to
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NNRTIs do not bind to the active site of the polymerase but in a less conserved pocket near the active site in the p66 subdomain. Their binding results in a conformational change in the reverse transcriptase that distorts the positioning of the residues that bind DNA, inhibiting polymerization.
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needed to synthesize the viral DNA and they compete with the natural deoxynucleotides for incorporation into the growing viral DNA chain. However, unlike the natural deoxynucleotides substrates, NRTIs and NtRTIs lack a 3β€²-hydroxyl group on the deoxyribose moiety. As a result, following
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Ren, J; Nichols, C; Bird, L; Chamberlain, P; Weaver, K; Short, S; Stuart, DI; Stammers, DK (2001). "Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors".
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Arion, D; Kaushik, N; McCormick, S; Borkow, G; Parniak, MA (1998). "Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase".
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Shafer, RW; Kozal, MJ; Winters, MA; Iversen, AK; Katzenstein, DA; Ragni, MV; Meyer, WA III; Gupta, P; et al. (1994). "Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of
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Das, K; Ding, J; Hsiou, Y; Clark Jr, AD; Moereels, H; Koymans, L; Andries, K; Pauwels, R; et al. (1996). "Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant".
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Das, Kalyan; Sarafianos, SG; Clark Jr, AD; Boyer, PL; Hughes, SH; Arnold, E (2007). "Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097".
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Nucleoside analog reverse-transcriptase inhibitors (NARTIs or NRTIs) compose the first class of antiretroviral drugs developed. In order to be incorporated into the viral DNA, NRTIs must be activated in the cell by the addition of three
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Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are the third class of antiretroviral drugs that were developed. In all cases, patents remain in force until beyond 2007. This class of drugs was first described at the
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Maeda, Y; Venzon, DJ; Mitsuya, H (1998). "Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance".
2198: 229:, also called FTC, has the trade name Emtriva (formerly Coviracil). Structurally similar to lamivudine, it is approved for the treatment of HIV and undergoing clinical trials for hepatitis B. 2203: 301:
step, but host enzymes must still phosphorylate the phosphonate nucleotide analogue to the phosphonate-diphosphate state for anti-viral activity. These molecules were first synthesized by
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Hsiou, Y; Ding, J; Das, K; Clark Jr, AD; Boyer, PL; Lewi, P; Janssen, PA; Kleim, JP; et al. (2001). "The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance".
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Ren, J; Esnouf, R; Garman, E; Somers, D; Ross, C; Kirby, I; Keeling, J; Darby, G; et al. (1995). "High resolution structures of HIV-1 RT from four RT-inhibitor complexes".
1785: 451: 2155: 2213: 2133: 241:, made of emtricitabine and tenofovir disoproxil fumarate, is used to treat and prevent HIV. It is approved for HIV prevention in the US and manufactured by Gilead. 193:, also called AZT, ZDV, and azidothymidine, has the trade name Retrovir. Zidovudine was the first antiretroviral drug approved by the FDA for the treatment of HIV. 2218: 447: 2166: 1567: 2188: 2172: 3217: 2183: 3640: 2193: 2627: 2460: 2104: 755:
Hachiya, A; Kodama, EN; Schuckmann, MM; Kirby, KA; Michailidis, E; Sakagami, Y; Oka, S; Singh, K; Sarafianos, SG (2011). Ambrose, Zandrea (ed.).
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While often listed in chronological order, NRTIs/NtRTIs are nucleoside/nucleotide analogues of cytidine, guanosine, thymidine and adenosine:
330:. It is not approved by the FDA for treatment of HIV due to toxicity issues, but a lower dose is approved for the treatment of hepatitis B. 199:, also called ddI, with the trade names Videx and Videx EC, was the second FDA-approved antiretroviral drug. It is an analog of adenosine. 489:
Researchers have designed molecules which dually inhibit both reverse transcriptase (RT) and integrase (IN). These drugs are a type of "
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enzymes. NRTIs can induce mitochondrial impairment that leads to a number of adverse events, including symptomatic lactic acidosis.
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bond needed to extend the DNA chain. Thus, when an NRTI or NtRTI is incorporated, viral DNA synthesis is halted, a process known as
578:"Bench-to-bedside review: Severe lactic acidosis in HIV patients treated with nucleoside analogue reverse transcriptase inhibitors" 235:, also called ETV, is a guanosine analog used for hepatitis B under the trade name Baraclude. It is not approved for HIV treatment. 3512: 2233: 2117: 700:
Derbalah, Abdallah; Karpick, Hayley Christine; Maize, Holly; Skersick, Preston; Cottrell, Mackenzie; Rao, Gauri G. (2022-07-01).
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in 2017 and is currently used on its own or in fixed-dose combination with tenofovir disoproxil and emtricitabine (Elpida Combi).
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De Clercq, E (1998). "The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection".
3472: 3379: 2123: 1113:"A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase" 3566: 3400: 1545: 3599: 3591: 2620: 1553: 3495: 3485: 3467: 3408: 3312: 3178: 2576: 461: 217:, also called 3TC, has the trade name Zeffix and Epivir. It is approved for the treatment of both HIV and hepatitis B. 205:, also called ddC and dideoxycytidine, has the trade name Hivid. This drug has been discontinued by the manufacturer. 822:"Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids" 3349: 3291: 3254: 3203: 923:"Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy" 162: 1276:; Pillay, D; Schapiro, JM; Richman, DD (2009). "Update of the drug resistance mutations in HIV-1: December 2009". 3615: 3438: 3304: 306: 3571: 3433: 2660: 2400: 2310: 2178: 2139: 1539: 2605: 1071:"The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase" 3546: 3524: 3490: 3249: 3166: 2613: 2564: 2160: 1535: 3507: 3477: 3443: 3416: 3328: 3244: 2781: 2238: 3556: 3113: 3062: 2918: 2435: 2248: 2128: 1998: 1597: 683:"Elpida Combi (tenofovir+elsulfavirine+emtricitabine) Film-Coated Tablets. Full Prescribing Information" 490: 138: 58: 3057: 2914: 2144: 1993: 1751: 833: 768: 3421: 3336: 3043: 3006: 2758: 2253: 2112: 1984: 1902: 1701: 1580: 541: 129:
incorporation of an NRTI or an NtRTI, the next incoming deoxynucleotide cannot form the next 5′–3β€²
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Iversen, AK; Shafer, RW; Wehrly, K; Winters, MA; Mullins, JI; Chesebro, B; Merigan, TC (1996).
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The second mechanism is the excision or the hydrolytic removal of the incorporated drug or
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of NRTIs and NtRTIs is essentially the same; they are analogues of the naturally occurring
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analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs) directly obviates the initial
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Sarafianos, SG; Das, K; Clark Jr, AD; Ding, J; Boyer, PL; Hughes, SH; Arnold, E (1999).
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Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors
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Claessens, Yann-Erick; Chiche, Jean-Daniel; Mira, Jean-Paul; Cariou, Alain (2003).
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It is orally available, long acting antiviral, being tested as ART against HIV-1.
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Matsumi, S; Kosalaraksa, P; Tsang, H; Kavlick, MF; Harada, S; Mitsuya, H (2003).
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When HIV infects a cell, reverse transcriptase copies the viral single stranded
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Proceedings of the National Academy of Sciences of the United States of America
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Discovery and development of non-nucleoside reverse-transcriptase inhibitors
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Nucleotide analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs)
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groups to their deoxyribose moiety, to form NRTI triphosphates. This
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has the trade name Edurant, and was approved by the FDA in May 2011.
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Nucleoside analog reverse-transcriptase inhibitors (NARTIs or NRTIs)
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Gao, HQ; Boyer, PL; Sarafianos, SG; Arnold, E; Hughes, SH (2000).
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has the trade name Intelence, and was approved by the FDA in 2008.
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Nucleoside reverse transcriptase translocation inhibitor (NRTTIs).
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being the first agent of this group. Islatravir was developed by
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Nucleoside reverse transcriptase translocation inhibitor (NRTTIs)
326:, also known as ADV or bis-POM PMPA, has trade names Preveon and 161:
the process of DNA synthesis. NNRTIs are therefore classified as
1644: 1632: 282:) for both viral and host DNA, causing respectively the desired 46: 3199: 2609: 1549: 702:"Role of islatravir in HIV treatment and prevention: an update" 1669: 1584: 82: 78: 42: 1111:
Meyer, PR; Matsuura, SE; Mian, AM; So, AG; Scott, WA (1999).
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Mechanisms of resistance to reverse transcriptase inhibitors
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Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide
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analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs)
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Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil
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Boyer, PL; Sarafianos, SG; Arnold, E; Hughes, SH (2001).
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It was FDA-approved in August 2018. It is also used in a
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analog reverse-transcriptase inhibitors (NARTIs or NRTIs)
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Darunavir/cobicistat/emtricitabine/tenofovir alafenamide
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Non-nucleoside reverse-transcriptase inhibitors (NNRTIs)
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Non-nucleoside reverse-transcriptase inhibitors (NNRTIs)
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Johnson, VA; Brun-Vezinet, F; Clotet, B; Gunthard, HF;
424:, currently rarely used, has the trade name Rescriptor. 211:, also called d4T, has trade names Zerit and Zerit XR. 278:
analogs. The latter serve as poison building blocks (
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doravirine/lamivudine/tenofovir disoproxil fumarate
809:from the original on Mar 17, 2022 – via PMC. 65:that is required for replication of HIV and other 968:from the original on Jul 3, 2024 – via PMC. 2156:Dolutegravir/emtricitabine/tenofovir alafenamide 2214:Emtricitabine/rilpivirine/tenofovir alafenamide 2134:Bictegravir/emtricitabine/tenofovir alafenamide 2219:Emtricitabine/rilpivirine/tenofovir disoproxil 1705:(Integrase strand transfer inhibitors (INSTI)) 473:This is a new class of antivirals, MK-8591 or 3211: 2621: 2167:Dolutegravir/lamivudine/tenofovir alafenamide 1561: 442:has the trade name Pifeltro, is developed by 149:for both. The former explains NRTIs'/NtRTIs' 8: 2189:Efavirenz/emtricitabine/tenofovir disoproxil 2173:Dolutegravir/lamivudine/tenofovir disoproxil 3277: 3218: 3204: 3196: 3075: 2693: 2683: 2674: 2665: 2628: 2614: 2606: 2287: 2184:Doravirine/lamivudine/tenofovir disoproxil 2021: 1887: 1792: 1568: 1554: 1546: 460:, sold as Elpida, was approved by Russian 2194:Efavirenz/lamivudine/tenofovir disoproxil 1538:at the U.S. National Library of Medicine 1177: 1128: 1106: 1104: 1037: 948: 938: 857: 847: 837: 792: 782: 772: 603: 593: 137:. All NRTIs and NtRTIs are classified as 2461:Zinc finger protein transcription factor 412:has the trade names Sustiva and Stocrin. 1015: 1013: 1011: 557: 629:"Elsulfavirine: First Global Approval" 89:referred to as polymerase inhibitors. 7: 627:Al-Salama, Zaina T. (October 2017). 81:genome into a double-stranded viral 2209:Emtricitabine/tenofovir alafenamide 687:Russian State Register of Medicines 399:Rega Institute for Medical Research 2224:Emtricitabine/tenofovir disoproxil 982:The Journal of Infectious Diseases 888:The Journal of Infectious Diseases 153:, while the latter explains their 25: 3641:Reverse transcriptase inhibitors 2597:. Formerly or rarely used agent. 2234:Lamivudine/nevirapine/zidovudine 2118:Abacavir/dolutegravir/lamivudine 1536:Reverse+Transcriptase+Inhibitors 1170:10.1128/JVI.75.10.4832-4842.2001 1039:10.1097/00002030-200305230-00003 182:step is carried out by cellular 139:competitive substrate inhibitors 31:Reverse-transcriptase inhibitors 18:Reverse-transcriptase inhibitors 2401:Epigallocatechin gallate (EGCG) 2244:Lamivudine/tenofovir disoproxil 2229:Lamivudine/nevirapine/stavudine 940:10.1128/JVI.70.2.1086-1090.1996 706:Current Opinion in HIV and AIDS 267:As described above, host cells 2124:Abacavir/lamivudine/zidovudine 1: 1251:10.1016/S0166-3542(98)00025-4 1130:10.1016/S1097-2765(00)80185-9 1457:Journal of Molecular Biology 1421:Journal of Molecular Biology 1385:Journal of Molecular Biology 1341:Journal of Molecular Biology 1075:Journal of Molecular Biology 784:10.1371/journal.pone.0016242 718:10.1097/COH.0000000000000740 418:has the trade name Viramune. 27:Class of antiretroviral drug 1999:Tenofovir alafenamide (TAF) 3657: 3396:Dihydropteroate synthetase 3255:Non-competitive inhibition 1994:Tenofovir disoproxil (TDF) 288:drug toxicity/side effects 165:of reverse transcriptase. 163:non-competitive inhibitors 155:drug toxicity/side effects 3616:Steroidogenesis inhibitor 3156: 2554: 2015:Discovery and development 1786:Discovery and development 1622:Discovery and development 1492:Nature Structural Biology 1318:10.1016/j.jmb.2006.08.097 645:10.1007/s40265-017-0820-3 307:Czech Academy of Sciences 97:RTIs come in four forms: 3552:Matrix metalloproteinase 3355:Ribonucleotide reductase 3250:Uncompetitive inhibition 2311:Transcription inhibitors 2263:Pharmacokinetic boosters 2179:Dolutegravir/rilpivirine 2140:Cabotegravir/rilpivirine 1780:Protease Inhibitors (PI) 1540:Medical Subject Headings 900:10.1093/infdis/169.4.722 849:10.1073/pnas.96.18.10027 309:, and commercialized by 3321:Dihydrofolate reductase 3079:Nucleic acid inhibitors 2595:initial regimen options 2161:Dolutegravir/lamivudine 1638:Enfuvirtide (ENF, T-20) 1616:Entry/fusion inhibitors 3417:Nucleotidyltransferase 3245:Competitive inhibition 2436:Portmanteau inhibitors 2329:Translation inhibitors 2239:Lamivudine/raltegravir 2009:Non-nucleoside (NNRTI) 1967:Islatravir (EFdA, ISL) 1469:10.1006/jmbi.1998.2171 1433:10.1006/jmbi.1996.0698 1397:10.1006/jmbi.2001.4988 1353:10.1006/jmbi.2001.4648 1278:Topics in HIV Medicine 1087:10.1006/jmbi.2000.3823 491:portmanteau inhibitors 485:Portmanteau inhibitors 3427:Reverse transcriptase 3114:Peginterferon alfa-2a 3063:Tenofovir alafenamide 2451:Synergistic enhancers 2249:Lamivudine/zidovudine 2129:Atazanavir/cobicistat 2105:Combined formulations 1942:Zidovudine (AZT, ZDV) 1880:Reverse-transcriptase 1752:Maturation inhibitors 375:Adenosine analogues: 364:Guanosine analogues: 349:Cytidine analogues: 338:Thymidine analogues: 59:reverse transcriptase 3473:Acetylcholinesterase 3380:Thymidylate synthase 3058:Tenofovir disoproxil 3044:Nucleotide analogues 3007:Nucleoside analogues 2292:Uncoating inhibitors 2145:Darunavir/cobicistat 1985:Nucleotide analogues 1903:Nucleoside analogues 1702:Integrase inhibitors 1581:antiretroviral drugs 49:, and in some cases 39:antiretroviral drugs 3567:Histone deacetylase 3401:Farnesyltransferase 2759:Pyrimidine analogue 2284:Experimental agents 2254:Lopinavir/ritonavir 2113:Abacavir/lamivudine 2087:Elsulfavirine (ESV) 1922:Emtricitabine (FTC) 1808:Fosamprenavir (FPV) 1504:10.1038/nsb0495-293 1158:Journal of Virology 927:Journal of Virology 839:1999PNAS...9610027S 774:2011PLoSO...616242H 542:Protease inhibitors 73:Mechanism of action 3600:Carbonic anhydrase 3592:Dopa decarboxylase 3260:Suicide inhibition 3183:Never to phase III 3109:Interferon alfa 2b 2581:Never to phase III 1727:Elvitegravir (EVG) 1722:Dolutegravir (DTG) 1717:Cabotegravir (CAB) 1239:Antiviral Research 516:pyrophosphorolysis 462:Ministry of Health 448:combination tablet 3628: 3627: 3624: 3623: 3496:Alpha-glucosidase 3486:Polygalacturonase 3468:Phosphodiesterase 3409:GABA transaminase 3313:Monoamine oxidase 3297:HMG-CoA reductase 3231:enzyme inhibition 3193: 3192: 3152: 3151: 2991: 2990: 2909: 2908: 2857: 2856: 2837: 2836: 2603: 2602: 2550: 2549: 2396:Diarylpyrimidines 2099: 2098: 2095: 2094: 2075:Rilpivirine (RPV) 2059:diarylpyrimidines 2042:Delavirdine (DLV) 1937:Zalcitabine (ddC) 1894:nucleotide (NRTI) 1874: 1873: 1732:Raltegravir (RAL) 1712:Bictegravir (BIC) 1691:Fostemsavir (FTR) 1606:Lenacapavir (LEN) 1598:Capsid inhibitors 1216:10.1021/bi981200e 886:gene mutations". 639:(16): 1811–1816. 280:chain terminators 147:chain terminators 135:chain termination 37:) are a class of 16:(Redirected from 3648: 3350:Xanthine oxidase 3292:Aldose reductase 3278: 3265:Mixed inhibition 3220: 3213: 3206: 3197: 3123:Multiple/unknown 3076: 3072:Multiple/general 2842:Not TK activated 2694: 2684: 2675: 2666: 2630: 2623: 2616: 2607: 2421:Hydroxycarbamide 2288: 2082:Doravirine (DOR) 2070:Etravirine (ETR) 2065:Dapivirine (DPV) 2037:Nevirapine (NVP) 2022: 1927:Lamivudine (3TC) 1917:Didanosine (ddI) 1888: 1861:Tipranavir (TPV) 1849:Atazanavir (ATV) 1833:Saquinavir (SQV) 1823:Nelfinavir (NFV) 1803:Amprenavir (APV) 1793: 1675:Ibalizumab (IBA) 1570: 1563: 1556: 1547: 1524: 1523: 1487: 1481: 1480: 1451: 1445: 1444: 1415: 1409: 1408: 1379: 1373: 1372: 1336: 1330: 1329: 1300: 1294: 1293: 1269: 1263: 1262: 1234: 1228: 1227: 1210:(45): 15908–17. 1198: 1192: 1191: 1181: 1149: 1143: 1142: 1132: 1108: 1099: 1098: 1066: 1060: 1059: 1041: 1017: 1006: 1005: 976: 970: 969: 967: 952: 942: 918: 912: 911: 878: 872: 871: 861: 851: 841: 832:(18): 10027–32. 817: 811: 810: 796: 786: 776: 752: 746: 745: 697: 691: 690: 679: 673: 672: 624: 618: 617: 607: 597: 573: 567: 562: 522:NNRTI resistance 284:antiviral effect 151:antiviral effect 126:deoxynucleotides 122:antiviral effect 21: 3656: 3655: 3651: 3650: 3649: 3647: 3646: 3645: 3631: 3630: 3629: 3620: 3604: 3576: 3452: 3439:Tyrosine kinase 3359: 3269: 3233: 3224: 3194: 3189: 3188: 3173:Clinical trials 3148: 3118: 3095: 3067: 2987: 2964: 2940: 2936:Podophyllotoxin 2905: 2853: 2833: 2753: 2698:Purine analogue 2679: 2655: 2634: 2604: 2599: 2598: 2586: 2571:Clinical trials 2546: 2497:Dexelvucitabine 2465: 2456:Tre recombinase 2359: 2341: 2323: 2319:Tat antagonists 2305: 2279: 2258: 2091: 2046: 2032:Efavirenz (EFV) 2011: 2003: 1932:Stavudine (d4T) 1893: 1881: 1870: 1855:Darunavir (DRV) 1837: 1828:Ritonavir (RTV) 1818:Lopinavir (LPV) 1813:Indinavir (IDV) 1782: 1774: 1746: 1704: 1696: 1650:Maraviroc (MVC) 1618: 1610: 1592: 1577:Antiviral drugs 1574: 1532: 1527: 1489: 1488: 1484: 1453: 1452: 1448: 1427:(5): 1085–100. 1417: 1416: 1412: 1381: 1380: 1376: 1338: 1337: 1333: 1302: 1301: 1297: 1271: 1270: 1266: 1236: 1235: 1231: 1200: 1199: 1195: 1164:(10): 4832–42. 1151: 1150: 1146: 1110: 1109: 1102: 1068: 1067: 1063: 1019: 1018: 1009: 978: 977: 973: 965: 920: 919: 915: 880: 879: 875: 819: 818: 814: 754: 753: 749: 699: 698: 694: 681: 680: 676: 626: 625: 621: 575: 574: 570: 563: 559: 555: 533: 524: 508: 506:NRTI resistance 499: 487: 479:Merck & Co. 471: 444:Merck & Co. 394: 299:phosphorylation 265: 180:phosphorylation 171: 95: 75: 28: 23: 22: 15: 12: 11: 5: 3654: 3652: 3644: 3643: 3633: 3632: 3626: 3625: 3622: 3621: 3619: 3618: 3612: 3610: 3606: 3605: 3603: 3602: 3595: 3594: 3587: 3585: 3578: 3577: 3575: 3574: 3572:Beta-lactamase 3569: 3562: 3561: 3560: 3559: 3554: 3549: 3539: 3538: 3537: 3532: 3522: 3521: 3520: 3515: 3499: 3498: 3493: 3488: 3481: 3480: 3475: 3470: 3463: 3461: 3454: 3453: 3451: 3450: 3449: 3448: 3447: 3446: 3434:Protein kinase 3431: 3430: 3429: 3424: 3412: 3411: 3404: 3403: 3398: 3391: 3390: 3383: 3382: 3377: 3370: 3368: 3361: 3360: 3358: 3357: 3352: 3345: 3344: 3339: 3332: 3331: 3324: 3323: 3316: 3315: 3308: 3307: 3300: 3299: 3294: 3287: 3285: 3282:Oxidoreductase 3275: 3271: 3270: 3268: 3267: 3262: 3257: 3252: 3247: 3241: 3239: 3235: 3234: 3225: 3223: 3222: 3215: 3208: 3200: 3191: 3190: 3187: 3186: 3185: 3184: 3181: 3170: 3164: 3158: 3157: 3154: 3153: 3150: 3149: 3147: 3146: 3141: 3132: 3126: 3124: 3120: 3119: 3117: 3116: 3111: 3105: 3103: 3097: 3096: 3094: 3093: 3088: 3082: 3080: 3073: 3069: 3068: 3066: 3065: 3060: 3055: 3039: 3038: 3033: 3028: 3023: 3018: 3002: 3000: 2993: 2992: 2989: 2988: 2986: 2985: 2980: 2974: 2972: 2966: 2965: 2963: 2962: 2950: 2948: 2942: 2941: 2939: 2938: 2933: 2923: 2921: 2911: 2910: 2907: 2906: 2904: 2903: 2898: 2886: 2881: 2876: 2871: 2865: 2863: 2859: 2858: 2855: 2854: 2852: 2851: 2845: 2843: 2839: 2838: 2835: 2834: 2832: 2831: 2818: 2817: 2816: 2815: 2810: 2805: 2792: 2791: 2785: 2775: 2763: 2761: 2755: 2754: 2752: 2751: 2738: 2737: 2727: 2725:Valganciclovir 2718: 2702: 2700: 2691: 2681: 2672: 2663: 2657: 2656: 2635: 2633: 2632: 2625: 2618: 2610: 2601: 2600: 2585: 2584: 2583: 2582: 2579: 2568: 2562: 2556: 2555: 2552: 2551: 2548: 2547: 2545: 2544: 2539: 2534: 2529: 2524: 2519: 2514: 2509: 2504: 2499: 2494: 2489: 2484: 2479: 2473: 2471: 2467: 2466: 2464: 2463: 2458: 2453: 2448: 2443: 2438: 2433: 2428: 2423: 2418: 2413: 2408: 2403: 2398: 2393: 2388: 2383: 2378: 2373: 2367: 2365: 2361: 2360: 2358: 2357: 2351: 2349: 2343: 2342: 2340: 2339: 2333: 2331: 2325: 2324: 2322: 2321: 2315: 2313: 2307: 2306: 2304: 2303: 2296: 2294: 2285: 2281: 2280: 2278: 2277: 2272: 2270:Cobicistat (c) 2266: 2264: 2260: 2259: 2257: 2256: 2251: 2246: 2241: 2236: 2231: 2226: 2221: 2216: 2211: 2206: 2201: 2196: 2191: 2186: 2181: 2176: 2170: 2164: 2158: 2153: 2147: 2142: 2137: 2131: 2126: 2121: 2115: 2109: 2107: 2101: 2100: 2097: 2096: 2093: 2092: 2090: 2089: 2084: 2079: 2078: 2077: 2072: 2067: 2054: 2052: 2048: 2047: 2045: 2044: 2039: 2034: 2028: 2026: 2019: 2005: 2004: 2002: 2001: 1996: 1980: 1979: 1974: 1969: 1964: 1959: 1954: 1949: 1944: 1939: 1934: 1929: 1924: 1919: 1914: 1912:Abacavir (ABC) 1898: 1896: 1892:Nucleoside and 1885: 1876: 1875: 1872: 1871: 1869: 1868: 1863: 1858: 1852: 1845: 1843: 1839: 1838: 1836: 1835: 1830: 1825: 1820: 1815: 1810: 1805: 1799: 1797: 1790: 1776: 1775: 1773: 1772: 1767: 1762: 1756: 1754: 1748: 1747: 1745: 1744: 1739: 1734: 1729: 1724: 1719: 1714: 1708: 1706: 1698: 1697: 1695: 1694: 1682: 1666: 1652: 1641: 1628: 1626: 1612: 1611: 1609: 1608: 1602: 1600: 1594: 1593: 1575: 1573: 1572: 1565: 1558: 1550: 1544: 1543: 1531: 1530:External links 1528: 1526: 1525: 1498:(4): 293–302. 1482: 1446: 1410: 1391:(4): 795–805. 1374: 1331: 1295: 1264: 1229: 1193: 1144: 1117:Molecular Cell 1100: 1061: 1032:(8): 1127–37. 1007: 994:10.1086/515282 988:(5): 1207–13. 971: 933:(2): 1086–90. 913: 873: 812: 747: 712:(4): 240–246. 692: 674: 619: 595:10.1186/cc2162 588:(3): 226–232. 568: 556: 554: 551: 550: 549: 544: 539: 532: 529: 523: 520: 507: 504: 498: 495: 486: 483: 470: 467: 466: 465: 455: 437: 431: 425: 419: 413: 393: 390: 389: 388: 373: 362: 347: 332: 331: 321: 264: 261: 260: 259: 242: 236: 230: 224: 218: 212: 206: 200: 194: 170: 167: 131:phosphodiester 118: 117: 114: 111: 105: 94: 91: 74: 71: 63:DNA polymerase 41:used to treat 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 3653: 3642: 3639: 3638: 3636: 3617: 3614: 3613: 3611: 3609:Miscellaneous 3607: 3601: 3597: 3596: 3593: 3589: 3588: 3586: 3583: 3579: 3573: 3570: 3568: 3564: 3563: 3558: 3555: 3553: 3550: 3548: 3547:Enkephalinase 3545: 3544: 3543: 3540: 3536: 3533: 3531: 3528: 3527: 3526: 3525:Endopeptidase 3523: 3519: 3516: 3514: 3511: 3510: 3509: 3505: 3501: 3500: 3497: 3494: 3492: 3491:Neuraminidase 3489: 3487: 3483: 3482: 3479: 3476: 3474: 3471: 3469: 3465: 3464: 3462: 3459: 3455: 3445: 3442: 3441: 3440: 3437: 3436: 3435: 3432: 3428: 3425: 3423: 3420: 3419: 3418: 3414: 3413: 3410: 3406: 3405: 3402: 3399: 3397: 3393: 3392: 3389: 3385: 3384: 3381: 3378: 3376: 3372: 3371: 3369: 3366: 3362: 3356: 3353: 3351: 3347: 3346: 3343: 3340: 3338: 3334: 3333: 3330: 3326: 3325: 3322: 3318: 3317: 3314: 3310: 3309: 3306: 3302: 3301: 3298: 3295: 3293: 3289: 3288: 3286: 3283: 3279: 3276: 3272: 3266: 3263: 3261: 3258: 3256: 3253: 3251: 3248: 3246: 3243: 3242: 3240: 3236: 3232: 3228: 3221: 3216: 3214: 3209: 3207: 3202: 3201: 3198: 3182: 3180: 3177: 3176: 3174: 3171: 3168: 3165: 3163: 3160: 3159: 3155: 3145: 3142: 3140: 3136: 3133: 3131: 3128: 3127: 3125: 3121: 3115: 3112: 3110: 3107: 3106: 3104: 3102: 3098: 3092: 3091:Brincidofovir 3089: 3087: 3084: 3083: 3081: 3077: 3074: 3070: 3064: 3061: 3059: 3056: 3054: 3051: 3049: 3045: 3041: 3040: 3037: 3034: 3032: 3029: 3027: 3024: 3022: 3019: 3017: 3014: 3012: 3008: 3004: 3003: 3001: 2998: 2994: 2984: 2981: 2979: 2976: 2975: 2973: 2971: 2967: 2961: 2958: 2956: 2952: 2951: 2949: 2947: 2943: 2937: 2934: 2932: 2928: 2925: 2924: 2922: 2920: 2916: 2912: 2902: 2899: 2896: 2892: 2891: 2890:early protein 2887: 2885: 2882: 2880: 2877: 2875: 2872: 2870: 2867: 2866: 2864: 2860: 2850: 2847: 2846: 2844: 2840: 2829: 2825: 2824: 2820: 2819: 2814: 2811: 2809: 2806: 2804: 2801: 2800: 2799: 2798: 2794: 2793: 2789: 2786: 2783: 2779: 2776: 2774: 2770: 2769: 2765: 2764: 2762: 2760: 2756: 2749: 2745: 2744: 2740: 2739: 2735: 2731: 2728: 2726: 2722: 2719: 2717: 2713: 2709: 2708: 2704: 2703: 2701: 2699: 2695: 2692: 2689: 2685: 2682: 2678:DNA-synthesis 2676: 2673: 2671: 2667: 2664: 2662: 2658: 2653: 2649: 2645: 2641: 2638: 2631: 2626: 2624: 2619: 2617: 2612: 2611: 2608: 2596: 2593: 2590: 2580: 2578: 2575: 2574: 2572: 2569: 2566: 2563: 2561: 2558: 2557: 2553: 2543: 2540: 2538: 2535: 2533: 2530: 2528: 2525: 2523: 2520: 2518: 2515: 2513: 2510: 2508: 2505: 2503: 2500: 2498: 2495: 2493: 2490: 2488: 2485: 2483: 2480: 2478: 2475: 2474: 2472: 2470:Failed agents 2468: 2462: 2459: 2457: 2454: 2452: 2449: 2447: 2444: 2442: 2439: 2437: 2434: 2432: 2429: 2427: 2424: 2422: 2419: 2417: 2414: 2412: 2409: 2407: 2404: 2402: 2399: 2397: 2394: 2392: 2389: 2387: 2384: 2382: 2379: 2377: 2374: 2372: 2369: 2368: 2366: 2362: 2356: 2353: 2352: 2350: 2348: 2344: 2338: 2337:Trichosanthin 2335: 2334: 2332: 2330: 2326: 2320: 2317: 2316: 2314: 2312: 2308: 2301: 2298: 2297: 2295: 2293: 2289: 2286: 2282: 2276: 2275:Ritonavir (r) 2273: 2271: 2268: 2267: 2265: 2261: 2255: 2252: 2250: 2247: 2245: 2242: 2240: 2237: 2235: 2232: 2230: 2227: 2225: 2222: 2220: 2217: 2215: 2212: 2210: 2207: 2205: 2202: 2200: 2197: 2195: 2192: 2190: 2187: 2185: 2182: 2180: 2177: 2174: 2171: 2168: 2165: 2162: 2159: 2157: 2154: 2151: 2148: 2146: 2143: 2141: 2138: 2135: 2132: 2130: 2127: 2125: 2122: 2119: 2116: 2114: 2111: 2110: 2108: 2106: 2102: 2088: 2085: 2083: 2080: 2076: 2073: 2071: 2068: 2066: 2063: 2062: 2061: 2060: 2056: 2055: 2053: 2049: 2043: 2040: 2038: 2035: 2033: 2030: 2029: 2027: 2023: 2020: 2018: 2016: 2010: 2006: 2000: 1997: 1995: 1992: 1990: 1986: 1982: 1981: 1978: 1975: 1973: 1970: 1968: 1965: 1963: 1960: 1958: 1955: 1953: 1950: 1948: 1945: 1943: 1940: 1938: 1935: 1933: 1930: 1928: 1925: 1923: 1920: 1918: 1915: 1913: 1910: 1908: 1904: 1900: 1899: 1897: 1895: 1889: 1886: 1883: 1877: 1867: 1864: 1862: 1859: 1856: 1853: 1850: 1847: 1846: 1844: 1840: 1834: 1831: 1829: 1826: 1824: 1821: 1819: 1816: 1814: 1811: 1809: 1806: 1804: 1801: 1800: 1798: 1794: 1791: 1789: 1787: 1781: 1777: 1771: 1768: 1766: 1763: 1761: 1758: 1757: 1755: 1753: 1749: 1743: 1740: 1738: 1735: 1733: 1730: 1728: 1725: 1723: 1720: 1718: 1715: 1713: 1710: 1709: 1707: 1703: 1699: 1692: 1688: 1687: 1683: 1680: 1676: 1672: 1671: 1667: 1664: 1660: 1656: 1653: 1651: 1647: 1646: 1642: 1639: 1635: 1634: 1630: 1629: 1627: 1625: 1623: 1617: 1613: 1607: 1604: 1603: 1601: 1599: 1595: 1590: 1586: 1583:used against 1582: 1578: 1571: 1566: 1564: 1559: 1557: 1552: 1551: 1548: 1541: 1537: 1534: 1533: 1529: 1521: 1517: 1513: 1509: 1505: 1501: 1497: 1493: 1486: 1483: 1478: 1474: 1470: 1466: 1463:(2): 313–23. 1462: 1458: 1455:resistance". 1450: 1447: 1442: 1438: 1434: 1430: 1426: 1422: 1414: 1411: 1406: 1402: 1398: 1394: 1390: 1386: 1378: 1375: 1370: 1366: 1362: 1358: 1354: 1350: 1347:(2): 437–45. 1346: 1342: 1335: 1332: 1327: 1323: 1319: 1315: 1311: 1307: 1299: 1296: 1291: 1287: 1284:(5): 138–45. 1283: 1279: 1275: 1274:Kuritzkes, DR 1268: 1265: 1260: 1256: 1252: 1248: 1245:(3): 153–79. 1244: 1240: 1233: 1230: 1225: 1221: 1217: 1213: 1209: 1205: 1197: 1194: 1189: 1185: 1180: 1175: 1171: 1167: 1163: 1159: 1155: 1148: 1145: 1140: 1136: 1131: 1126: 1122: 1118: 1114: 1107: 1105: 1101: 1096: 1092: 1088: 1084: 1081:(2): 403–18. 1080: 1076: 1072: 1065: 1062: 1057: 1053: 1049: 1045: 1040: 1035: 1031: 1027: 1023: 1016: 1014: 1012: 1008: 1003: 999: 995: 991: 987: 983: 975: 972: 964: 960: 956: 951: 946: 941: 936: 932: 928: 924: 917: 914: 909: 905: 901: 897: 893: 889: 885: 877: 874: 869: 865: 860: 855: 850: 845: 840: 835: 831: 827: 823: 816: 813: 808: 804: 800: 795: 790: 785: 780: 775: 770: 767:(1): e16242. 766: 762: 758: 751: 748: 743: 739: 735: 731: 727: 723: 719: 715: 711: 707: 703: 696: 693: 689:(in Russian). 688: 684: 678: 675: 670: 666: 662: 658: 654: 650: 646: 642: 638: 634: 630: 623: 620: 615: 611: 606: 601: 596: 591: 587: 583: 582:Critical Care 579: 572: 569: 566: 561: 558: 552: 548: 545: 543: 540: 538: 535: 534: 530: 528: 521: 519: 517: 512: 505: 503: 496: 494: 492: 484: 482: 480: 476: 468: 463: 459: 458:Elsulfavirine 456: 453: 449: 445: 441: 438: 435: 432: 429: 426: 423: 420: 417: 414: 411: 408: 407: 406: 404: 400: 391: 386: 382: 378: 374: 371: 367: 363: 360: 359:emtricitabine 356: 352: 348: 345: 341: 337: 336: 335: 329: 325: 322: 319: 316: 315: 314: 312: 308: 304: 300: 296: 293: 289: 285: 281: 277: 273: 270: 269:phosphorylate 262: 258: 254: 250: 246: 243: 240: 237: 234: 231: 228: 227:Emtricitabine 225: 222: 219: 216: 213: 210: 207: 204: 201: 198: 195: 192: 189: 188: 187: 185: 181: 177: 168: 166: 164: 158: 156: 152: 148: 144: 143:DNA synthesis 140: 136: 132: 127: 123: 115: 112: 109: 106: 103: 100: 99: 98: 92: 90: 86: 84: 80: 72: 70: 68: 64: 60: 56: 52: 48: 45:infection or 44: 40: 36: 32: 19: 3541: 3508:Exopeptidase 3478:Ribonuclease 3444:Janus kinase 3426: 3329:Lipoxygenase 3305:5Ξ±-Reductase 3227:Pharmacology 3130:Filociclovir 3042: 3005: 2953: 2901:Tromantadine 2888: 2821: 2795: 2778:Trifluridine 2766: 2741: 2716:Valaciclovir 2705: 2591: 2391:Cyanovirin-N 2381:Calanolide A 2057: 2051:2 generation 2025:1 generation 2012: 1983: 1962:Elvucitabine 1952:Apricitabine 1901: 1891: 1879: 1842:2 generation 1796:1 generation 1783: 1770:Fipravirimat 1684: 1679:Semzuvolimab 1668: 1659:Cenicriviroc 1643: 1631: 1619: 1495: 1491: 1485: 1460: 1456: 1449: 1424: 1420: 1413: 1388: 1384: 1377: 1344: 1340: 1334: 1312:(1): 77–89. 1309: 1305: 1298: 1281: 1277: 1267: 1242: 1238: 1232: 1207: 1204:Biochemistry 1203: 1196: 1161: 1157: 1147: 1123:(1): 35–43. 1120: 1116: 1078: 1074: 1064: 1029: 1025: 985: 981: 974: 930: 926: 916: 894:(4): 722–9. 891: 887: 883: 876: 829: 825: 815: 764: 760: 750: 709: 705: 695: 686: 677: 636: 632: 622: 585: 581: 571: 560: 525: 513: 509: 500: 488: 472: 454:(Delstrigo). 395: 333: 303:Antonin Holy 266: 172: 159: 145:, acting as 119: 96: 87: 76: 67:retroviruses 57:activity of 34: 30: 29: 3557:Oxytocinase 3365:Transferase 3169:from market 3139:Taribavirin 3031:Telbivudine 2997:Hepatitis B 2983:Tecovirimat 2978:Methisazone 2773:Idoxuridine 2734:Famciclovir 2730:Penciclovir 2721:Ganciclovir 2670:Herpesvirus 2661:Baltimore I 2642:(primarily 2592:recommended 2567:from market 2517:Lersivirine 2492:Capravirine 2431:Miltefosine 2416:Griffithsin 2411:Fosdevirine 1957:Censavudine 1587:(primarily 434:Rilpivirine 422:Delavirdine 383:(TDF), and 357:(3TC), and 351:zalcitabine 292:phosphonate 274:analogs to 253:hepatitis C 203:Zalcitabine 51:hepatitis B 3144:Moroxydine 3101:Interferon 3021:Lamivudine 2970:Poxviridae 2960:Rifampicin 2931:Resiquimod 2895:Fomivirsen 2879:Letermovir 2869:Amenamevir 2828:Cytarabine 2813:Sorivudine 2782:+tipiracil 2748:Vidarabine 2640:antivirals 2522:Lodenosine 2502:Droxinavir 2487:Brecanavir 2482:Atevirdine 2446:Seliciclib 2441:Scytovirin 2355:Elipovimab 2300:TRIM5alpha 1977:Stampidine 1882:inhibitors 1866:TMC-310911 1765:BMS-955176 1663:Leronlimab 1655:Vicriviroc 1306:J Mol Biol 565:Islatravir 553:References 475:Islatravir 440:Doravirine 428:Etravirine 416:Nevirapine 377:didanosine 368:(ABC) and 355:lamivudine 342:(AZT) and 340:zidovudine 295:nucleotide 276:nucleotide 272:nucleoside 257:SARS-CoV-2 215:Lamivudine 197:Didanosine 191:Zidovudine 108:Nucleotide 102:Nucleoside 61:, a viral 3458:Hydrolase 3422:Integrase 3337:Aromatase 3274:Substrate 3179:Phase III 3167:Withdrawn 3135:Ribavirin 3086:Cidofovir 3036:Clevudine 3026:Lobucavir 3016:Entecavir 2927:Imiquimod 2884:Maribavir 2874:Docosanol 2849:Foscarnet 2803:Brivudine 2788:Edoxudine 2712:Aciclovir 2690:activated 2680:inhibitor 2637:DNA virus 2577:Phase III 2565:Withdrawn 2542:Telinavir 2537:Palinavir 2532:Mozenavir 2512:Emivirine 2507:Lasinavir 2477:Aplaviroc 2406:Foscarnet 2386:Ceragenin 1947:Amdoxovir 1760:Bevirimat 1737:BI 224436 742:250078665 726:1746-6318 653:0012-6667 410:Efavirenz 381:tenofovir 370:entecavir 344:stavudine 318:Tenofovir 290:. Taking 233:Entecavir 209:Stavudine 176:phosphate 3635:Category 3504:Protease 3053:Adefovir 2955:assembly 2946:Vaccinia 2823:cytosine 2527:Loviride 1520:34618424 1405:11575933 1361:11371163 1326:17056061 1290:20068260 1188:11312355 1139:10445025 1095:10873473 1056:21484628 1048:12819513 963:Archived 868:10468556 807:Archived 803:21249155 761:PLOS ONE 734:35762379 669:25316512 661:28940154 614:12793872 531:See also 385:adefovir 366:abacavir 324:Adefovir 245:Azvudine 221:Abacavir 3530:Trypsin 2797:thymine 2768:uridine 2743:adenine 2707:guanine 2646:, also 2426:KP-1461 1972:Racivir 1742:MK-2048 1512:7540934 1477:9813120 1441:9000632 1369:3109889 1259:9754886 1224:9843396 1002:9593005 959:8551567 908:8133086 834:Bibcode 794:3020970 769:Bibcode 403:Belgium 379:(ddI), 353:(ddC), 328:Hepsera 305:at the 239:Truvada 55:inhibit 53:. RTIs 3584:(EC 4) 3460:(EC 3) 3367:(EC 2) 3327:1.13 3284:(EC 1) 3162:WHO-EM 3048:NtRTIs 3011:NARTIs 2808:FV-100 2560:WHO-EM 2376:BIT225 2371:Abzyme 2302:(gene) 1989:NtRTIs 1884:(RTIs) 1542:(MeSH) 1518:  1510:  1475:  1439:  1403:  1367:  1359:  1324:  1288:  1257:  1222:  1186:  1179:114238 1176:  1137:  1093:  1054:  1046:  1000:  957:  950:189915 947:  906:  866:  856:  801:  791:  740:  732:  724:  667:  659:  651:  612:  605:270672 602:  311:Gilead 255:, and 184:kinase 3582:Lyase 3542:Mixed 3535:Renin 3513:DPP-4 3348:1.17 3342:COX-2 3335:1.14 3238:Class 2999:(VII) 2862:Other 2652:D06BB 2648:S01AD 2364:Other 2347:BNAbs 1907:NRTIs 1686:gp120 1516:S2CID 1365:S2CID 1052:S2CID 966:(PDF) 859:17836 738:S2CID 665:S2CID 633:Drugs 387:(ADV) 372:(ETV) 361:(FTC) 346:(d4T) 93:Types 3598:4.2 3590:4.1 3565:3.5 3502:3.4 3484:3.2 3466:3.1 3415:2.7 3407:2.6 3394:2.5 3388:PARP 3386:2.4 3375:COMT 3373:2.1 3319:1.5 3311:1.4 3303:1.3 3290:1.1 2650:and 2589:DHHS 1645:CCR5 1633:gp41 1508:PMID 1473:PMID 1437:PMID 1401:PMID 1357:PMID 1322:PMID 1286:PMID 1255:PMID 1220:PMID 1184:PMID 1135:PMID 1091:PMID 1044:PMID 1026:AIDS 998:PMID 955:PMID 904:PMID 864:PMID 799:PMID 730:PMID 722:ISSN 657:PMID 649:ISSN 610:PMID 286:and 249:AIDS 120:The 47:AIDS 35:RTIs 3518:ACE 2915:HPV 2644:J05 1670:CD4 1589:J05 1585:HIV 1500:doi 1465:doi 1461:284 1429:doi 1425:264 1393:doi 1389:312 1349:doi 1345:309 1314:doi 1310:365 1247:doi 1212:doi 1174:PMC 1166:doi 1125:doi 1083:doi 1079:300 1034:doi 990:doi 986:177 945:PMC 935:doi 896:doi 892:169 884:pol 854:PMC 844:doi 789:PMC 779:doi 714:doi 641:doi 600:PMC 590:doi 493:". 450:as 405:). 83:DNA 79:RNA 43:HIV 3637:: 3506:: 3229:: 3175:: 2919:MC 2688:TK 2573:: 1677:, 1661:, 1657:, 1579:: 1514:. 1506:. 1494:. 1471:. 1459:. 1435:. 1423:. 1399:. 1387:. 1363:. 1355:. 1343:. 1320:. 1308:. 1282:17 1280:. 1253:. 1243:38 1241:. 1218:. 1208:37 1206:. 1182:. 1172:. 1162:75 1160:. 1156:. 1133:. 1119:. 1115:. 1103:^ 1089:. 1077:. 1073:. 1050:. 1042:. 1030:17 1028:. 1024:. 1010:^ 996:. 984:. 961:. 953:. 943:. 931:70 929:. 925:. 902:. 890:. 862:. 852:. 842:. 830:96 828:. 824:. 805:. 797:. 787:. 777:. 763:. 759:. 736:. 728:. 720:. 710:17 708:. 704:. 685:. 663:. 655:. 647:. 637:77 635:. 631:. 608:. 598:. 584:. 580:. 313:. 251:, 157:. 69:. 3219:e 3212:t 3205:v 3137:/ 3050:: 3046:/ 3013:: 3009:/ 2957:: 2929:/ 2917:/ 2897:) 2893:( 2830:) 2826:( 2790:) 2784:) 2780:( 2771:( 2750:) 2746:( 2736:) 2732:/ 2723:/ 2714:/ 2710:( 2654:) 2629:e 2622:t 2615:v 2587:Β° 2175:Β° 2169:Β° 2163:Β° 2152:Β° 2136:Β° 2120:Β° 2017:) 2013:( 1991:: 1987:/ 1909:: 1905:/ 1857:Β° 1851:Β° 1788:) 1784:( 1693:) 1689:( 1681:) 1673:( 1665:) 1648:( 1640:) 1636:( 1624:) 1620:( 1591:) 1569:e 1562:t 1555:v 1522:. 1502:: 1496:2 1479:. 1467:: 1443:. 1431:: 1407:. 1395:: 1371:. 1351:: 1328:. 1316:: 1292:. 1261:. 1249:: 1226:. 1214:: 1190:. 1168:: 1141:. 1127:: 1121:4 1097:. 1085:: 1058:. 1036:: 1004:. 992:: 937:: 910:. 898:: 870:. 846:: 836:: 781:: 771:: 765:6 744:. 716:: 671:. 643:: 616:. 592:: 586:7 401:( 33:( 20:)

Index

Reverse-transcriptase inhibitors
antiretroviral drugs
HIV
AIDS
hepatitis B
inhibit
reverse transcriptase
DNA polymerase
retroviruses
RNA
DNA
Nucleoside
Nucleotide
antiviral effect
deoxynucleotides
phosphodiester
chain termination
competitive substrate inhibitors
DNA synthesis
chain terminators
antiviral effect
drug toxicity/side effects
non-competitive inhibitors
phosphate
phosphorylation
kinase
Zidovudine
Didanosine
Zalcitabine
Stavudine

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