Rudi Pauwels

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Rudi Pauwels
Rudi Pauwels.jpg
Dr. Rudi Pauwels
Born1960
NationalityBelgian
EducationPh.D. in pharmaceutical sciences
Alma mater KU Leuven
Occupation(s)Pharmaceutical scientist and biotech entrepreneur
Organization(s)Praesens Foundation, Praesens Care, miDiagnostics
AwardsPrix Galien MedStartUpAward (2019), Global Technology Pioneer Award (2012), INSEAD Innovator Prize (2002)

Rudi Pauwels (born 1960) is a Belgian pharmacologist and biotech entrepreneur. [1]

Contents

He was one of the first researchers in the field of HIV, and he played a key role in the fight against the AIDS pandemic by discovering several widely used anti-HIV drugs during his doctorate studies at the Rega Institute (Leuven, Belgium) and while leading biotech companies Tibotec and Virco. [2]

Since 1994 he has either founded or co-founded several biotech companies, specialising in personalized and high precision medicine. His current roles include founder and president of the Praesens Foundation, chairman of Praesens Care, executive chairman of IMEC/Johns Hopkins spin-off company miDiagnostics and board positions in various companies and research institutes. He is an author of more than 150 peer-reviewed papers and recipient of numerous awards and distinctions. [3] [4]

In 2020 he was appointed as co-chair of the Diagnostics R&D Working Group of the Access to COVID-19 Tools Accelerator. [5] [ failed verification ] [6]

Education and early research

He studied pharmaceutical sciences at the Katholieke Universiteit Leuven (KU Leuven), Belgium, and graduated as a pharmacist in 1983.[ citation needed ]

Within a year after the 1983 discovery of HIV, the viral pathogen that causes AIDS, [7] Pauwels began work on the topic while still a doctorate student. In 1984, in the laboratory of Professor Erik De Clercq at the Rega Institute (University of Leuven, Belgium), he started to develop the first laboratory models in search of new anti-HIV compounds. The methods he published were widely used by fellow scientists that joined the search for new anti-AIDS (HIV) treatments. [8]

In 1987, Pauwels obtained a research fellowship of the Janssen Research Foundation, which started a long-standing collaboration and close friendship with the late Dr. Paul Janssen, founder of Janssen Pharmaceuticals. Janssen became a mentor and would influence his pharmaceutical work. In 1990, the Janssen-funded collaboration of his small team at the Rega Institute would lead to the discovery of the first non-nucleoside reverse transcriptase inhibitor (NNRTI). It was also Janssen who would introduce him to Dr. Paul Stoffels, with whom he would collaborate at Tibotec, Virco and Johnson & Johnson. [8]

Pauwels obtained his Ph.D. in pharmaceutical sciences from the KU Leuven in 1990 with greatest distinction ( maxima cum laude ), with De Clercq and Janssen as his promotors. His thesis was entitled "Development of new agents against the Human Immunodeficiency Virus (HIV)". [9]

Career

Tibotec, Virco and Johnson & Johnson

A few years after obtaining his Ph.D. and leading a small group of researchers at the Rega Institute, Pauwels began to work on the problem of HIV drug resistance. In 1994, he founded the anti-HIV drug discovery company Tibotec together with his wife, pharmacist Carine Claeys.

A year later they founded, together with Paul Stoffels, the diagnostics company Virco, which would develop HIV-treatment diagnostic services that would help physicians select the optimal therapy for their patients (e.g. Antivirogram). [10]

Tibotec-Virco was acquired by Johnson & Johnson in 2002, after which Pauwels became vice president of Johnson & Johnson's global anti-infectives drug discovery group, focusing on Hepatitis C and respiratory diseases. Here, he worked on drugs and diagnostics for respiratory diseases. In the middle of the SARS crisis in 2003, he started a project to develop an anti-SARS drug discovery system that, in 2020, was used as the basis for efforts to find inhibitors for SARS-CoV-2.[ as of? ] [11] This effort, involving a number of pharmaceutical companies, occurred at the Rega Institute, continuing the work based on his original large-scale anti-HIV drug screening and recently[ as of? ] received funding from the Bill & Melinda Gates Foundation.

The work of Pauwels and his colleagues resulted in several drugs that were successfully introduced for modern antiviral AIDS therapies. They include next-generation anti-HIV compounds by Tibotec/Johnson & Johnson,  Prezista, Intelence and Edurant, as well as the direct precursor to Gilead Sciences' Viread. These drugs, together with the diagnostic technologies by Virco, have helped to turn AIDS into the chronic, manageable disease it is today,[ when? ] for those who have access to the medicines. The drugs have also generated several billion dollar revenues yearly, providing returns for investors and shareholders and helping to finance the R&D for the treatment of important diseases. [10]

In 1999, Pauwels was one of the driving forces behind the creation of the Tibotec spin-out, Galapagos Genomics, that would combine functional genomic technologies from Tibotec and Crucell, a Dutch-based biotech company. [12] [ when? ]

Biocartis

In early 2000, it became clear to Pauwels that the future of medicine was increasingly depending on our molecular insights of disease. New generations of drugs would target the underlying molecular dysfunctional processes. It meant that measuring relevant biomarkers would become even more essential. But experiences from the global AIDS crisis and Virco in particular, taught him that the operational model of sending samples from patients to central laboratories was time-consuming and wasteful. It appeared that his approach did not scale easily around the world. Ideally, the lab functionality needed to come (in miniaturized format) to patients and their direct environment, not the other way around.

During his Ph.D. studies, he broadened his interests beyond virology into software programming and robotics. Realizing the need for better, scalable diagnostics at the point of need, he decided in 2004 to go on a three-year sabbatical at the Swiss Federal Institute of Technology-EPFL in Lausanne (Switzerland), one of the leading research centres in micro- and nano-technology.

In 2007, he created Biocartis, a molecular diagnostics company that would develop and commercialize the Idylla platform, a fully integrated and automated sample-to-molecular diagnostic (PCR) result solution. The company grew rapidly and was taken public. The company offered precision diagnostics for cancer therapies, but there was ultimately no broader support for his expansion plans into infectious diseases. After leading the company for a decade, he decided in 2017 to further pursue his interests in infectious diseases.

Praesens Foundation

During the Ebola outbreak in 2014 and 2015, and after spending the better part of his life in laboratories, Pauwels wanted to observe first hand how the world was dealing with outbreaks of that scale. He saw the need for rapid, accurate and easy-to-use diagnostics close to the affected communities.

Inspired by this experience in West Africa, in 2016 he created the Praesens Fund under the Belgian King Baudouin Foundation. The name is related to the Latin word praesens, meaning 'being here now, making an impact'. With the help of a series of early believers – among which passionate collaborators, sponsors and technology providers – the initial sketch of a first-generation mobile lab was soon made a reality.

As the project entered the next stage in 2017, Pauwels created the Praesens Foundation, co-directed by Professor Peter Piot. It is developing, providing and implementing solutions that contribute to better epidemic preparedness, early warning and rapid response for existing and emerging infectious disease threats. In 2017 and 2018, an initial pilot study led by the Praesens Foundation deployed the first all-terrain Mobile Biosafety Laboratory for infectious disease testing across Senegal. It offers rapid deployment, connectivity and technology for effective field diagnostics, reducing turn-around time and improving case management. This has potential to improve epidemic preparedness and contribute to disease intelligence. [13]

The latest initiative is Praesens Care. Through this venture it intends to expand geographically and functionally. Praesens Care offers "lab as a service" (LAAS). Praesens Care offers mobile biosafety laboratories in a regional hub approach to countries and partners to reinforce their healthcare delivery system, with integrated diagnostic services (multi-disease testing and real-time reporting), primary healthcare and community engagement. It offers an outreach capacity to provide medical (e.g. diagnostics, therapies, vaccination) and non-medical (health promotion, social mobilization) services at the peripheral level of the health system, as close as possible to the communities. [14] [ when? ]

miDiagnostics

In 2018, Pauwels was appointed executive chairman of miDiagnostics, a large life science spin-off company of IMEC and Johns Hopkins University. IMEC is a nano-electronics R&D hub with more than 4,000 engineers and scientists headquartered in Leuven, Belgium. Based on nearly a decade of IMEC research on nano-fluidics and silicon-based nanostructures, miDiagnostics is developing a next generation diagnostic platform with broad in vitro diagnostics applications, particular in the point of care area. It is developing a series of new nanofluidic silicon processors that are embedded in test cards – about the size of a credit card – and that are inserted in a compact reader. [15] [ as of? ]

Investment experience

In 2007, Pauwels joined Advent Partners, a venture capital firm in London. He assisted Advent in reviewing investment opportunities and supported several portfolio companies. [16] He was involved in the formation of Respivert Ltd., where he acted as chairman of the board. Respivert was a molecule drug discovery company working towards the identification of new treatments for patients with chronic obstructive pulmonary disease. Respivert was acquired by Johnson & Johnson in 2010. [17]

Other professional roles

Personal life

Pauwels is the father of actress Eline Powell. [18] [19]

Awards and recognition

Selected publications

Pauwels is an author or co-author of more than 150 papers in peer-reviewed journals. [4] A selected list is shown below by topic.

Related Research Articles

<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.

<span class="mw-page-title-main">Zidovudine</span> Antiretroviral medication

Zidovudine (ZDV), also known as azidothymidine (AZT), was the first antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child spread during birth or after a needlestick injury or other potential exposure. It is sold both by itself and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It can be used by mouth or by slow injection into a vein.

The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.

Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS, hepatitis C and COVID-19. These protease inhibitors prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.

Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses.

<span class="mw-page-title-main">Tenofovir disoproxil</span> Antiviral drug used to treat or prevent HIV and hepatitis infections

Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention of HIV/AIDS among those at high risk before exposure, and after a needlestick injury or other potential exposure. It is sold both by itself and together in combinations such as emtricitabine/tenofovir, efavirenz/emtricitabine/tenofovir, and elvitegravir/cobicistat/emtricitabine/tenofovir. It does not cure HIV/AIDS or hepatitis B. It is available by mouth as a tablet or powder.

<span class="mw-page-title-main">Nelfinavir</span> Antiretroviral drug

Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is almost always used in combination with other antiretroviral drugs.

<span class="mw-page-title-main">Tibotec</span>

Tibotec was a pharmaceutical company with a focus on research and development of the treatment of infectious diseases such as HIV/AIDS and hepatitis C. The company was founded in 1994 and then acquired by Johnson & Johnson and merged into its Janssen Pharmaceuticals division in 2002. The company is part of Johnson & Johnson Innovation Medicine business segment.

<span class="mw-page-title-main">Rega Institute for Medical Research</span> Belgian biomedical research institute

The Rega Institute for Medical Research is a Belgian scientific establishment that is part of the Catholic University of Leuven (Leuven) in central Belgium. The Rega Institute is an interfacultary biomedical research institute of the Catholic University of Leuven and consists of departments of medicine and pharmacology.

<span class="mw-page-title-main">HIV-1 protease</span> Enzyme involved with peptide bond hydrolysis in retroviruses

HIV-1 protease or PR is a retroviral aspartyl protease (retropepsin), an enzyme involved with peptide bond hydrolysis in retroviruses, that is essential for the life-cycle of HIV, the retrovirus that causes AIDS. HIV-1 PR cleaves newly synthesized polyproteins at nine cleavage sites to create the mature protein components of an HIV virion, the infectious form of a virus outside of the host cell. Without effective HIV-1 PR, HIV virions remain uninfectious.

<span class="mw-page-title-main">Etravirine</span> Medication used for the treatment of HIV

Etravirine (ETR,), sold under the brand name Intelence is an antiretroviral medication used for the treatment of HIV. Etravirine is a human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine. Etravirine is marketed by Janssen, a subsidiary of Johnson & Johnson. In January 2008, the US Food and Drug Administration (FDA) approved its use for people with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008. It was also approved for use in Canada in April 2008.

<span class="mw-page-title-main">Diarylpyrimidines</span> Class of chemical compounds

Diarylpyrimidines (DAPY) and diaryltriazines (DATA) are two closely related classes of molecules resembling the pyrimidine nucleotides found in DNA. They show great potency in inhibiting the activity of HIV reverse transcriptase. Several compounds in this class are non-nucleoside reverse transcriptase inhibitors used clinically in the treatment of HIV/AIDS, notably etravirine and rilpivirine.

Paul J. Lewi was a Belgian scientist, who elaborated Spectral Map Analysis in 1975 and was one of the cofounders of chemometrics in 1983. Paul Lewi was married with Godelieve Debruyne and they have together 3 children and with Philomena Van Bylen, with 2 children.

<span class="mw-page-title-main">Subtypes of HIV</span> Variants of the human immunodeficiency virus

The subtypes of HIV include two main subtypes, known as HIV type 1 (HIV-1) and HIV type 2 (HIV-2). These subtypes have distinct genetic differences and are associated with different epidemiological patterns and clinical characteristics.

Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are antiretroviral drugs used in the treatment of human immunodeficiency virus (HIV). NNRTIs inhibit reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of HIV. RT is one of the most popular targets in the field of antiretroviral drug development.

Many major physiological processes depend on regulation of proteolytic enzyme activity and there can be dramatic consequences when equilibrium between an enzyme and its substrates is disturbed. In this prospective, the discovery of small-molecule ligands, like protease inhibitors, that can modulate catalytic activities has an enormous therapeutic effect. Hence, inhibition of the HIV protease is one of the most important approaches for the therapeutic intervention in HIV infection and their development is regarded as major success of structure-based drug design. They are highly effective against HIV and have, since the 1990s, been a key component of anti-retroviral therapies for HIV/AIDS.

Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs.

<span class="mw-page-title-main">Erik De Clercq</span> American biochemist

Erik De Clercq M.D. Ph.D., (1941) is a Belgian physician and biologist. He studied medicine at the Catholic University of Leuven. He did research and later became a professor at the Department of Medicine, where he specialised in microbiology and immunology. He worked at the Rega Institute for Medical Research. He is one of the founders and the second president of the International Society for Antiviral Research.

Deborah Persaud is a Guyanese-born American virologist who primarily works on HIV/AIDS at Johns Hopkins Children's Center.

<span class="mw-page-title-main">Mozenavir</span> Chemical compound

Mozenavir (DMP-450) is an antiviral drug which was developed as a treatment for HIV/AIDS. It acts as an HIV protease inhibitor and binds to this target with high affinity, however despite promising results in early testing, mozenavir was unsuccessful in human clinical trials. Studies continue into related derivatives.

References

  1. ↑ "Coronavirus Global Response International Pledging Conference Countdown - Rudi Pauwels". global-response.europa.eu. Retrieved 4 February 2021.
  2. ↑ "Rudi Pauwels: Pionier in AIDS preventie en ziektedetectie" (PDF). Trends (in Dutch): 78–79. 2014 – via Knack.
  3. ↑ "Interview: "Het gebrek aan langetermijnvisie is de ziekte van deze tijd"". Trends. 1167021. 2018.
  4. 1 2 "Rudi Pauwels' research". ResearchGate. 2021. Retrieved 4 February 2021.
  5. 1 2 "About the ACT-Accelerator". FIND. Retrieved 4 February 2021.
  6. 1 2 "ACT Accelerator: global response to COVID-19. ACT-A Dx structure" (PDF). Global Health Hub. Retrieved 4 February 2021.
  7. ↑ Barré-Sinoussi, Françoise (20 May 1983). "Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)". Science. 220 (4599): 868–871. doi:10.1126/science.6189183. PMID   6189183 . Retrieved 29 January 2023.
  8. 1 2 De Clercq, Erik (November 2015). "An Odyssey in antiviral drug development—50 years at the Rega Institute: 1964–2014". Acta Pharmaceutica Sinica B. 5 (6): 520–543. doi:10.1016/j.apsb.2015.09.001. PMC   4675811 . PMID   26713268.
  9. ↑ "CV Erik De Clercq" (PDF). ICDDT. 2008. Retrieved 4 February 2021.
  10. 1 2 "Chance of a Lifetime: The story of Virco" (PDF). The Journal of Precision Medicine.
  11. 1 2 Ivens, Tania; Eynde, Christel Van den; Acker, Koen Van; Nijs, Erik; Dams, Géry; Bettens, Eva; Ohagen, Asa; Pauwels, Rudi; Hertogs, Kurt (1 October 2005). "Development of a homogeneous screening assay for automated detection of antiviral agents active against severe acute respiratory syndrome-associated coronavirus". Journal of Virological Methods. 129 (1): 56–63. doi:10.1016/j.jviromet.2005.05.010. ISSN   0166-0934. PMC   7112772 . PMID   15961169.
  12. ↑ "Galapagos: Our History". Glpg. Retrieved 4 February 2021.
  13. 1 2 Fall, Cheikh; Cappuyns, Aurélie; Faye, Oumar; Pauwels, Steven; Fall, Gamou; Dia, Ndongo; Diagne, Moussa M.; Diagne, Cheikh T.; Niang, Makhtar; Mbengue, Alassane; Faye, Martin (20 August 2020). "Field evaluation of a mobile biosafety laboratory in Senegal to strengthen rapid disease outbreak response and monitoring". African Journal of Laboratory Medicine. 9 (2): 1041. doi:10.4102/ajlm.v9i2.1041. ISSN   2225-2002. PMC   7479379 . PMID   32934915.
  14. ↑ "Labplus Africa - partnering against new emerging pandemics". The European-Security and Defence Union. 36. 2020 – via Issuu.
  15. ↑ "Urbain Vandeurzen en Rudi Pauwels investeren in Leuvens miDiagnostics". Trends-Knack. 25 March 2020. Retrieved 4 February 2021.
  16. ↑ "Advent appoints Rudi Pauwels to life sciences team". Unquote. 26 June 2007. Retrieved 5 February 2021.
  17. ↑ "Advent Sells Respivert to J&J for Significant Cash Return". Advent Life Sciences. Retrieved 5 February 2021.
  18. ↑ Vlaamse actrice Eline Powell steelt de show in Hollywoodreeks ‘Siren’
  19. ↑ Bobbin, Jay (20 January 2019). "Powell dives into 'Siren' role". Boston Herald. Retrieved 23 January 2019. Her pharmacologist father founded a biotech company (with her mother) in their homeland and a molecular diagnostic company in Switzerland, and he has been a leading force in the treatment of the HIV virus.
  20. ↑ "Praesens Foundation, Institut Pasteur, Institut Pasteur de Dakar, University of Nebraska Medical Center, Twist Bioscience Consortium Win Prix Galien MedStartUp Award". BusinessWire. 2019. Retrieved 4 February 2021.
  21. ↑ "Nieuwe adellijke gunsten en eretekens". Diplomatie Belgium (in Dutch). 2016. Retrieved 4 February 2021.
  22. ↑ "Plenary presentation "The Entrepreneurial Journey: Balancing Technological Exploration and Exploitation in the Pursuit of Breakthroughs in Medicine & Healthcare"". Select Biosciences. 2016. Retrieved 4 February 2021.
  23. ↑ "Spotlight on Rudi Pauwels: How to turn failures into success". A*STAR. Retrieved 4 February 2021.
  24. ↑ "Plenaire vergadering: Uitreiking van de Gouden Erepenningen 2016". Vlaams Parlement (in Dutch). Retrieved 4 February 2021.
  25. ↑ "Eerste FarmaLeuven alumnus van het jaar - Dr. Rudi Pauwels gehuldigd door Minister Maggie De Block op 14 November 2015" (PDF). FarmaLeuven (in Dutch). 2015. Retrieved 4 February 2021.
  26. ↑ "Uitreiking van de UGent eredoctoraten". Magazine Universiteit Gent (in Dutch). January 2013: 22 – via Issuu.
  27. ↑ "Eredoctoraten voor professoren Justin Lin en Françoise Tulkens aan UGent". Knack (in Dutch). Retrieved 4 February 2021.
  28. ↑ "Benoeming door Koninklijk besluit gepubliceerd op 18 december 2013". Etaamb (Belgisch Staatsblad) (in Dutch).
  29. ↑ "Technology Pioneers 2012 Report". World Economic Forum. 2012. Retrieved 4 February 2021.
  30. ↑ "BioAlps Awards: Prix Industrie". BioAlps. Retrieved 4 February 2021.
  31. ↑ "Verleihungen: AIDS forschungpreis (Awards: AIDS research award)" (PDF). Deutsches Ärzteblatt (in German). 93: 1420.
  32. ↑ Pauwels, R.; Schols, D. (1991). "Development of new potent and selective agents against HIV (human immunodeficiency virus)". Koninklijke Academie voor Geneeskunde van Belgïe. 53 (6): 629–655. PMID   1816706 – via Europe PMC.
  33. ↑ Pauwels, Rudi; De Clercq, Erik; Desmyter, Jan; Balzarini, Jan; Goubau, Patrick; Herdewijn, Piet; Vanderhaeghe, Hubert; Vandeputte, Michel (1 June 1987). "Sensitive and rapid assay on MT-4 cells for detection of antiviral compounds against the AIDS virus". Journal of Virological Methods. 16 (3): 171–185. doi:10.1016/0166-0934(87)90002-4. ISSN   0166-0934. PMID   2821048.
  34. ↑ Pauwels, Rudi; Balzarini, Jan; Baba, Masanori; Snoeck, Robert; Schols, Dominique; Herdewijn, Piet; Desmyter, Jan; De Clercq, Erik (1 August 1988). "Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds". Journal of Virological Methods. 20 (4): 309–321. doi:10.1016/0166-0934(88)90134-6. ISSN   0166-0934. PMID   2460479.
  35. ↑ Pauwels, R.; Balzarini, J.; Schols, D.; Baba, M.; Desmyter, J.; Rosenberg, I.; Holy, A.; Clercq, E. De (1 July 1988). "Phosphonylmethoxyethyl purine derivatives, a new class of anti-human immunodeficiency virus agents". Antimicrobial Agents and Chemotherapy. 32 (7): 1025–1030. doi: 10.1128/AAC.32.7.1025 . ISSN   0066-4804. PMC   172337 . PMID   2847636.
  36. ↑ Pauwels, Rudi; Andries, Koen; Desmyter, Jan; Schols, Dominique; Kukla, Michael J.; Breslin, Henry J.; Raeymaeckers, Alfons; Gelder, Jozef Van; Woestenborghs, Robert; Heykants, Jozef; Schellekens, Karel (February 1990). "Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives". Nature. 343 (6257): 470–474. Bibcode:1990Natur.343..470P. doi:10.1038/343470a0. ISSN   1476-4687. PMID   1689015. S2CID   4354080.
  37. ↑ Pauwels, R.; Andries, K.; Debyser, Z.; Van Daele, P.; Schols, D.; Stoffels, P.; De Vreese, K.; Woestenborghs, R.; Vandamme, A. M.; Janssen, C. G. (1 March 1993). "Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of alpha-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase". Proceedings of the National Academy of Sciences. 90 (5): 1711–1715. Bibcode:1993PNAS...90.1711P. doi: 10.1073/pnas.90.5.1711 . ISSN   0027-8424. PMC   45949 . PMID   7680476.
  38. ↑ Pauwels, Rudi (1 October 2004). "New non-nucleoside reverse transcriptase inhibitors (NNRTIs) in development for the treatment of HIV infections". Current Opinion in Pharmacology. 4 (5): 437–446. doi:10.1016/j.coph.2004.07.005. ISSN   1471-4892. PMID   15351347.
  39. ↑ Pauwels, Rudi (1993), Adams, Julian; Merluzzi, Vincent J. (eds.), "Discovery of TIBO, a New Family of HIV-1-Specific Reverse Transcriptase Inhibitors", The Search for Antiviral Drugs: Case Histories from Concept to Clinic, Boston, MA: Birkhäuser, pp. 71–104, doi:10.1007/978-1-4899-6718-3_4, ISBN   978-1-4899-6718-3 , retrieved 4 February 2021
  40. ↑ Hertogs, Kurt; Béthune, Marie-Pierre de; Miller, Veronica; Ivens, Tania; Schel, Patricia; Cauwenberge, Anja Van; Eynde, Christel Van den; Gerwen, Veerle van; Azijn, Hilde; Houtte, Margriet van; Peeters, Frank (1 February 1998). "A Rapid Method for Simultaneous Detection of Phenotypic Resistance to Inhibitors of Protease and Reverse Transcriptase in Recombinant Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Antiretroviral Drugs". Antimicrobial Agents and Chemotherapy. 42 (2): 269–276. doi: 10.1128/AAC.42.2.269 . ISSN   0066-4804. PMC   105399 . PMID   9527771.
  41. ↑ Meyer, Sandra De; Azijn, Hilde; Surleraux, Dominique; Jochmans, Dirk; Tahri, Abdellah; Pauwels, Rudi; Wigerinck, Piet; Béthune, Marie-Pierre de (1 June 2005). "TMC114, a Novel Human Immunodeficiency Virus Type 1 Protease Inhibitor Active against Protease Inhibitor-Resistant Viruses, Including a Broad Range of Clinical Isolates". Antimicrobial Agents and Chemotherapy. 49 (6): 2314–2321. doi: 10.1128/AAC.49.6.2314-2321.2005 . ISSN   0066-4804. PMC   1140553 . PMID   15917527.
  42. ↑ Surleraux, Dominique L. N. G.; Tahri, Abdellah; Verschueren, Wim G.; Pille, Geert M. E.; de Kock, Herman A.; Jonckers, Tim H. M.; Peeters, Anik; De Meyer, Sandra; Azijn, Hilde; Pauwels, Rudi; de Bethune, Marie-Pierre (1 March 2005). "Discovery and Selection of TMC114, a Next Generation HIV-1 Protease Inhibitor". Journal of Medicinal Chemistry. 48 (6): 1813–1822. doi:10.1021/jm049560p. ISSN   0022-2623. PMID   15771427.
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