Tomáš Cihlář

Tomáš Cihlář (born 1967) is a Czech biochemist known for his role in the development of remdesivir. A specialist in virology, Cihlář holds the positions of Senior Director, Biology, and Vice-President at American pharmaceutical company Gilead Sciences. As a student, Cihlář assisted fellow biochemist Antonín Holý in developing Viread, the primary drug used to fight HIV infection.[1]

Tomáš Cihlář
Born1967 (age 55–56)
Plzeň, Czechoslovakia (now Czech Republic)
NationalityCzech
Alma materUniversity of Chemistry and Technology, Prague
Occupation(s)Biochemist, virologist
Known forRemdesivir, tenofovir disoproxil

Education

Cihlář graduated from the University of Chemistry and Technology, Prague, majoring in fermentation chemistry and bioengineering under the tutelage of Jan Páca and Vladimír Jirků. He completed his postgraduate studies at the Institute of Organic Chemistry and Biochemistry of the ASCR under Ivan Rosenberg and Ivan Votruba. In 1994 he obtained the title of Candidate of Sciences and was engaged in the research of antiviral agents under the tutelage of Antonín Holý.

That same year, he traveled to the United States for a postdoctoral fellowship with Gilead Sciences, where as researcher he worked on the development of antiviral nucleotide analogs including tenofovir disoproxil fumarate, which, marketed as Viread, has become a primary drug in the fight against HIV infection.[2]

Career

At Gilead, leading a team of hundreds of scientists working on new substances for the treatment of HIV, viral hepatitis B, respiratory infections and other viral diseases such as Ebola, MERS, and dengue fever, Cihlář is as of 2020 responsible for biological research on HIV and respiratory viruses. On a number of these projects, he continues to work closely with scientists from the Institute of Organic Chemistry and Biochemistry, particularly Zdeněk Havlas and Zdeněk Hostomský,[3] and with the Radim Nencka Group,[4] which develops compounds capable of stopping the replication of important human pathogens by blocking the remodeling of cell membranes induced by these viruses.[5]

Cihlář is engaged in ongoing research into HIV inhibitors that target the enzyme integrase and prevent the formation of viral capsids.[6] Recently, these entail low molecular weight agonists of TLR7 (toll-like receptor 7).[7] TLR7 receptors recognize single-stranded RNA in endosomes and play a role in innate antiviral immunity. Such substances should help eliminate the HIV reservoir in T-lymphocytes and completely cure HIV patients.[5]

In 2006, Cihlář received a William Prusoff Young Investigator Lecture Award from the International Society for Antiviral Research for his work on antiviral nucleotide analogs. He has patented dozens of novel inventions.[8]

Remdesivir

Also at Gilead, Cihlář is one of the company's lead researchers in the development of remdesivir,[9][10] originally intended for treatment of Ebola. However, the Ebola epidemic ended before the new drug could be tested. Remdesivir briefly showed considerable promise in treating COVID-19 infection;[11] in April 2020 the company provided 5,000 doses for experimental use in China[12] and four hundred patients in 50 other countries.[13] Remdesivir was used to treat the first confirmed case of coronavirus in the U.S.[14][n 1]

In North Bethesda, Maryland, the National Institute of Allergy and Infectious Diseases conducted a trial involving 1,063 patients, some of whom were given the drug while others received a placebo. "The data shows remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery", NIAID director Dr. Anthony Fauci said.[15] "What it has proven is a drug can block this virus," Fauci added, "opening the door to the fact that we now have the capability of treating patients."[16] A week earlier, the WHO released, then retracted results from remdesivir trials in China finding the drug had "absolutely no benefit" for coronavirus patients.[17] Fauci stated that the WHO report was "not an adequate study", citing the fact that the trials were halted early due to a lack of volunteers.[18]

In early June 2020 it was reported that AstraZeneca, a British-Swedish multinational pharmaceutical and biopharmaceutical company headquartered in Cambridge, England, was pursuing a merger with Gilead due to a shared interest in the potential of remdesivir.[19]

In September 2020, following a review of purported evidence, the WHO’s guidelines committee issued a statement that there was no evidence of benefit, adding that Covid patients may be better off without it.[20] The statement, published in The BMJ, concludes, "Any beneficial effects of remdesivir, if they do exist, are likely to be small and the possibility of important harm remains.”[21] In October 2020, recognizing his involvement in the development of Remdesivir, which was thought potentially effective in treating Covid-19, Czech president Miloš Zeman awarded Cihlář the country's Silver Medal of Merit.[22]

In April 2021 Cihlář discussed the possibility of marketing remdesivir in pill form.[23]

References

Notes
  1. On January 21, 2020, the Wuhan Institute of Virology applied for a Chinese "use patent", for treatment of Covid-19.

Citations
  1. Czech News Agency, "Did Czech scientists create the cure for coronavirus?", Aktuálně.cz, February 05, 2020.
  2. Anon., Dr. Tomas Cihlar, HSTalks.
  3. Anon., The future of (not only) chemistry - ICT Conference: Tomáš Cihlář, Advances and new directions in the treatment of HIV infection, University of Chemistry and Technology, Prague.
  4. Římanová, R., Remdesivir: Naděje na zastavení koronaviru dostala v Česku zelenou—Akademie věd České republiky, Czech Academy of Sciences, March 18, 2020.
  5. Publikace Nencka group, Institute of Organic Chemistry and Biochemistry of the CAS.
  6. Anon., New Clinical Study Data for Gilead’s Investigational HIV-1 Capsid Inhibitor GS-6207 Presented at CROI 2020, Gilead Sciences, Inc., March 11, 2020
  7. Bam, Rujuta A.; Hansen, Derek; Irrinki, Alivelu; Mulato, Andrew; Jones, Gregg S.; Hesselgesser, Joseph; Frey, Christian R.; Cihlar, Tomas; Yant, Stephen R. (2017-01-01). "TLR7 Agonist GS-9620 Is a Potent Inhibitor of Acute HIV-1 Infection in Human Peripheral Blood Mononuclear Cells". Antimicrobial Agents and Chemotherapy. 61 (1). doi:10.1128/AAC.01369-16. ISSN 0066-4804. PMC 5192112. PMID 27799218.
  8. Patents by Inventor Tomas Cihlar, Justia Patents.
  9. Paulenková, K., Česká stopa v léku proti koronaviru. Naši chemici patří ke světové špičce, Mladá fronta DNES, February 8, 2020.
  10. Burrows, M. J., & Preble, C. A., "The Urgent Need to Adjust America’s Approach to the World", The National Interest, June 12, 2020.
  11. Holshue, M. L., Debolt, C., Lindquist, S., Lofy, K. H., Wiesman, J., Bruce, H., & Spitters, C., "First Case of 2019 Novel Coronavirus in the United States", The New England Journal of Medicine, March 5, 2020.
  12. Anon., "We sent test samples to China. The drug may arrive in May, says co-author of anti-coronavirus substance", ČT24. February 18, 2020.
  13. Rodriguez, V., "Lék na koronavirus? Vláda ho objednala od českého odborníka", Deník, March 16, 2020.
  14. Walker, J., "Gilead Sciences Offers Experimental Drug for Coronavirus Treatments, Testing", The Wall Street Journal, January 31, 2020.
  15. Gallagher, J., "Remdesivir: Drug has 'clear cut' power to fight coronavirus", BBC News, April 29, 2020.
  16. Fox, M., Gumbrecht, J., Yan, H., & Klein, B., "FDA will reportedly authorize use of remdesivir for Covid-19 after trial shows 'positive effect' on recovery time", CNN, April 30, 2020.
  17. Wang, Y., Zhang, D., Du, G., Du, R., Zhao, J., Jin, Y., et al., "Remdesivir in adults with severe Covid-19: a randomised, double-blind, placebo-controlled, multicentre trial", The Lancet, April 29, 2020.
  18. Ting, E., "Anthony Fauci reports 'quite good news' from Remdesivir trial with control group", San Francisco Chronicle, April 29, 2020.
  19. Lavička, V., "AstraZeneca má zájem o tvůrce léku Remdesivir—Rýsuje se největší fúze ve výrobě léčiv", Hospodářské noviny, June 9, 2020.
  20. Lamontagne F, Agoritsas T, Macdonald H, Leo YS, Diaz J, et al. (September 2020). "A living WHO guideline on drugs for covid-19". BMJ. 370: m3379. doi:10.1136/bmj.m3379. PMID 32887691.
  21. WHO guidelines panel, "A living WHO guideline on drugs for covid-19", British Medical Journal, September 4, 2020.
  22. Ly, N. T., "Zeman ocenil bojovníky proti koronaviru i veterány. Vyznamenání si odnese také Rychetský", E15, October 28, 2020.
  23. Zahradnická, E., "Remdesivir chceme dostat do tabletek. Funguje i na mutace, říká český vývojář", Mladá fronta DNES, April 21, 2021.

Further reading

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