Tenofovir is a medicine, that today is at the forefront for treatment of HIV and Heptatitis-B infection. Story of this drug, and its creators is however incredible. We knew only a little about HIV, at the time of discovery of this drug. At that time no one could have predicted that it will also work for another virus – Hepatitis B.
Its creators had sold the patent of this molecule to a pharma company, that had little interest in the molecule. So, patent went back to the institute where Antonin, its creator worked. Success of this molecule brought much needed revenue for the Institute of Organic Chemistry and Biochemistry (IOCB) located at Prague in Czech Republic. So Tenofovir, changed the face of IOCB, and brought accolades for its creator Antonin Holy.
Antonin and IOCB Prague
Antonin Holy was born, brought-up, and educated at Prague, then Czechoslovakia (and since 1993 Czech Republic). In 1953, Czechoslovakia had just emerged from second world war. Prof. František Šorm set up Institute of Organic Chemistry, with an aim to foster collaboration between scientists from varied backgrounds – chemistry, biology, and medicine. In 1960, Antonin joined the institute (by then named as Institute of Organic Chemistry and Biochemistry or IOCB), as a trainee. In 1967 he was a lead scientist at IOCB. By 1976, he was also collaborating with Prof. Erik De Clercq of the Rega Institute, Belgium on nucleosides and nucleic acids.
Building blocks of DNA and RNA
Nucleosides make up DNA and RNA of all living creatures, including viruses, bacteria, plants, animals and humans. Just four nucleobases guanine, adenine, cytosine, and thymine (and uracil in place of thymine in RNA) make up all of it. In 1970 David Baltimore and Howard Temin discovered enzymes called Reverse transcriptases which converts RNA to a DNA. This discovery not only led to award of 1975 Nobel Prize to Baltimore and Temin, but must have also motivated Holy and De Clercq to move a step further.
Tenofovir is Born
In 1984 Holý and De Clercq discovered Tenofovir, and submitted its first patent application. The creators initially thought that it will be useful for herpes virus. Meanwhile, scientists discovered HIV only in the previous year. However, by next year they had also found anti-HIV activity of this molecule in a cell culture. In 1987 they sold the patent to Bristol-Meyers, a US company, but by 1989 this company had a merger and acquisition with another pharma company Squibb. As the development of Tenofovir got stopped, the rights of the drug returned back to IOCB.
After a few years, John C. Martin (formerly at Bristol-Meyers Squibb) set up another company called Gilead in California. Thereafter, by 1997 the researchers had discovered anti-HIV effects of Tenofovir. This collaboration of Antonín Holý, Erik De Clercq, and John C. Martin established a long-lasting relationship between IOCB, the Rega Institute, and Gilead Sciences. Thus Tenofovir became a flagship drug, initially for treatment of HIV and thereafter for Hepatitis B. Today, this is the most common drug in use for treating these viral infections, and leads revenue stream for Gilead.
Epilogue
Antonin Holy headed IOCB from 1994 to 2002. The institute received more funds and went on to discover more drugs like Azacytidine and Decitabine , both used in treatment of cancers. Today IOCB Prague is an international success story. Antonin a celebrity in his own country, passed away in 2012. His Obituary that was published in Lancet a few months after his demise says:
“Antonin Holý was a very quiet person. He showed his satisfaction, but without making too much noise about it…..Initially forbidden to supervise students, he spent much of his earlier career working with the help of a single technician…. By nature he was extremely careful in all the work he did.“
Sir super history discovery by Antonin Holi narrated in a super fine manner thanks Sir for sharing the same 🌹🌹
Amazing story of Antonín Holý and his discovery Tenofovir for HIV. I visited his institute IOCB at Prague when I was invited to participate in the ISoP meeting in 2015. Stamps collection is superb on the theme. Recently, we had a guest lecture by Dr. Arshad Siddiqui, founder of Paraza Pharma Inc who shared his inspiring career trajectory including his professional experience at Shire-Biochem Pharma in Montreal, Canada, where he worked as a drug discovery scientist focused on virology, particularly HIV, and he co-invented the anti-HIV drug Lamivudine (3TC).
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