Raymond F. Schinazi (born 21 March 1950) is an Egyptian organic medicinal chemist. He is the Frances Winship Walters Professor of Pediatrics at Emory University. He has expertise in antiviral agents, pharmacology, and biotechnology. His research focuses on developing treatments for infections caused by human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV), herpes, dengue fever, zika, chikungunya, and other emerging viruses. These treatment options include antiviral agents as well as synthetic, biochemical, pharmacological and molecular genetic approaches, including molecular modeling and gene therapy. [1]
Schinazi was born on March 21, 1950, in Alexandria, Egypt to Jewish parents. [2] In 1962, his family was sequestered by the Nasser regime and in 1964 they immigrated to Naples, Italy as refugees. Schinazi went to boarding school in England where he completed his early education, before being admitted as an undergraduate at the University of Bath in 1968. He received his BSc in chemistry in 1972, and remained at Bath to complete his PhD in 1976. In 2006 he was awarded an honorary doctorate in Biotechnology from the University of Bath. In 1976, he moved to Yale University's department of pharmacology and trained as a postdoctoral fellow with William Prusoff. [3] [4] [5]
He also completed postdoctoral trainings in virology at the University of Chicago with Bernard Roizman and at University of North Carolina with Yung-Chi Cheng, and virology/immunology at Emory University with André Nahmias. [5]
Schinazi is currently the Frances Winship Walters Professor of Pediatrics, Director of the Laboratory of Biochemical Pharmacology, [5] and co-director of the HIV Cure Scientific Working Group within the NIH-sponsored Emory University Center for AIDS Research (CFAR) [6] in Atlanta, Georgia. He has served at Emory University for 39 years since 1978. [7] He also holds Adjunct Professor positions at both University of Georgia (Atlanta, GA) [8] and University of Miami (Miami, Florida). [9] He worked part-time for the Emory University affiliated Atlanta VA for 35 years while maintaining his Emory University appointment, retiring from the VA in 2016. [10]
He began his work as a herpes virologist with a specific focus on developing drug therapeutics for orolabial and genital herpes and severe life-threatening infections like herpes encephalitis. When HIV was identified as a virus in the 1980s, Schinazi and his fellow researchers directed their attention towards the problem. He was able to translate his knowledge gained through his work on the herpes viruses towards addressing HIV and HBV. He is credited for setting up the first-ever HIV laboratory at Emory University complete with a protocol on how to handle the dangerous virus in the laboratory setting so he and his team could pursue the development of novel antiviral drugs. [5] [11] In 1987, he helped Prusoff's laboratory discover that d4T, a nucleoside analog, had selective activity against HIV. [4] [12]
Schinazi is best known for his involvement in the discovery and development of innovative anti-HIV, HBV, and HCV drugs on the market. To date, he has been involved in the development of five FDA-approved drugs of which three are used in eight different drug combinations. [4] More than 94% of HIV-positive people take at least one of the drugs he invented. [10] [7] He has authored more than 550 peer-reviewed papers in academic literature with over 20,000 total citations. [13] [14]
Among the first drugs discovered and developed for treatment of HIV came through the collaboration between Dennis C. Liotta (Emory) and Schinazi. In 1992, they first published on lamivudine (3TC) in Antimicrobial Agents and Chemotherapy. [15] This drug became one of the most successful antiviral agents used to combat HIV as part of fixed-dose combinations (including Combivir, Trizivir, Epzicom, and Triumeq). Combination therapies incorporating 3TC quickly became the standard of care, with safe and effective nucleoside reverse transcriptase (RF) inhibitors, such as 3TC and its related cousins, serving as the cornerstones of combination chemotherapy. [16] [17] 3TC was also found to be active against HBV in collaboration with Drs. Dennis Liotta, Philip Furman and Yung-Chi Cheng. [18] [19] [20]
Schinazi's work led to the discovery of a second nucleoside analog, emtricitabine (FTC), subsequently resulting in a potent, safe nucleoside analog commonly used in treatment regimens. [21] The discovery of FTC was first published in 1992 in Antimicrobial Agents and Chemotherapy as another new anti-HIV compound. [22] The mechanism of action of FTC is by incorporation of FTC-TP into the growing viral DNA strand results in chain termination, disrupting viral DNA synthesis. Disruption of this process results in rapid reduction of systemic viral loads to undetectable in HIV-infected individuals, effectively allowing for significant rebound of CD4+ T-cells, effectively providing a tandem mechanism resulting in control of systemic viremia and restoration of functional immunity.
In addition, FTC in combination with tenofovir disoproxil fumarate (Truvada) was approved as a prophylactic drug (part of PrEP) to prevent transmission of HIV, further broadening its use beyond HIV-positive people to that of prophylaxis, underscoring a novel and previously unmet need with ramifications for global health worldwide. Today, this drug is widely used as part of fixed-dose combination drug regimens, including Truvada, Atripla, Complera, Stribild, Descovy, Genvoya, Odefsey, Descovy, Biktarvy, and Symtuza. [23] [20] Like 3TC, FTC was found to be active against HBV, but was never approved for this indication by the US FDA. [24] [25] [26] [27]
In 2004, Schinazi was one of the founders of Pharmasset, a company that would later go on to develop sofosbuvir. [28] The name Pharmasset was derived from 'pharmaceutical assets' and the original business plan was to create assets that would be sold to other companies. [29] The company raised around $45M in its 2007 IPO at $9 per share. It would later be taken over at $137 per share. In November 2011, Gilead Sciences announced a takeover bid for Pharmasset for approximately $11.4 billion. [30]
Schinazi's contribution to the discovery of sofosbuvir is contentious. He is the co-author of a 2005 paper that discovered a precursor to the drug. [31] Jean-Pierre Sommadossi, a principal founder of Idenix and a co-founder of Pharmasset, is a former business partner who no longer speaks to Schinazi. [31] [32]
In litigation between Idenix and Gilead/Pharmasset, there was an Order denying Idenix's motion for enhanced damages where the court noted that Schinazi "violated his confidentialy obligations to Idenix, and shared with Pharmasset scientists Idenix's proprietary discoveries relating to treatment of HCV". [33] However, even “fully accepting Idenix’s view of the evidence,” it was the company Schinazi founded, Pharmasset, not Idenix, that synthesized the key “compound that led to a cure for HCV.”. [34] Even accepting that Idenix discovered a component of the compound, the cure for HCV was discovered only after Pharmasset/Gilead's ”revolutionary refinement of that invention.” [35] Patent law, according to the order, reflects a balance between protection “and the importance of facilitating the imitation and refinement through imitation that are necessary to invention itself and the very lifeblood of a competitive economy.” [36]
In 2014, Schinazi, working with the Egyptian government and Gilead Sciences, agreed to provide Egypt with the drug Sofosbuvir (Sovaldi) for about US$1,000, which is only one percent of its market price. Also working with Pharco, an Egyptian Pharmaceutical company Sovaldi is now available for less than US$120 per cure. In Egypt, there is currently a total of around 12 million Egyptians infected with hepatitis C. [2]
Schinazi has also had a hand in the development of the other FDA-approved drugs stavudine and telbivudine. [31]
In 2018, Schinazi received the Chevalier de la Légion d’honneur, the French Legion of Honor, with the rank of knight. [37] Established in 1802 by Napoleon Bonaparte, it is the highest decoration bestowed in France and recognizes outstanding service to the French Republic. He is the recipient of numerous other awards, including: the Bruce Witte (Blumberg) Annual Distinguished Award- Hepatitis B Foundation (2000); [38] </ref> Distinguished Scientist Award- Hepatitis B Foundation (2006); [39] Emory University's Dean's Distinguished Faculty Lecture and Award (2008); [40] Inductee- Technology Hall of Fame of Georgia (2011); [41] Intellectual Property Legends Award- Georgia State University (2012);[ citation needed ] Charter Fellow- National Academy of Inventors (2013); [42] Distinguished Medical Science Award- Friends of the National Library of Medicine (2013); [43] </ref> Distinguished Scientific Achievement Award- American Liver Foundation (2014); [44] Research & Hope Award for Excellence in Academic Research- PhRMA Foundation (2014);[ citation needed ] William S. Middleton Award- US Veterans Affairs (2015); [45] Tom Glaser Leadership Award- Connexx Eagle Star Awards (2015); [10] Lifetime Achievement Award- Scrip Award, London (2016); [46] Lifetime Achievement Award for Public Service- Institute of Human Virology (2016). [47]
He also received the Intellectual Property Legends Award and is a charter fellow of the National Academy of Inventors, was inducted into the Technology Hall of Fame of Georgia, and the Georgia Biomedical Industry Growth Award.[ citation needed ] In 2023, Schinazi and colleagues received the "Deal of the Year" award from Emory's Office of Technology Transfer for their licensing agreement with Phizer, Inc. (https://www.linkedin.com/comm/feed/update/urn%3Ali%3Aactivity%3A7095106988258308096?midToken=AQFWcWc1Z4SzIg&midSig=0vhYSMs6SecGU1&trk=eml-email_notification_single_mentioned_you_in_this_01-notifications-1-hero~card~feed&trkEmail=eml-email_notification_single_mentioned_you_in_this_01-notifications-1-hero~card~feed-null-les7~ll4250kv~2q-null-voyagerOffline&lipi=urn%3Ali%3Apage%3Aemail_email_notification_single_mentioned_you_in_this_01%3B88Z45snOTeSqTd3iTz%2FYsg%3D%3D)
Schinazi has been a founder of:
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.
Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form, typically progressing from a long-lasting asymptomatic condition up to a decompensated hepatic disease and hepatocellular carcinoma (HCC).
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.
Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typically used in combination with other antiretrovirals such as zidovudine, dolutegravir, and abacavir. Lamivudine may be included as part of post-exposure prevention in those who have been potentially exposed to HIV. Lamivudine is taken by mouth as a liquid or tablet.
Emtricitabine, with trade name Emtriva, is a nucleoside reverse-transcriptase inhibitor (NRTI) for the prevention and treatment of HIV infection in adults and children. In 2019, it was the 494th most commonly prescribed medication in the United States, with more than 3 thousand prescriptions.
Entecavir, sold under the brand name Baraclude, is an antiviral medication used in the treatment of hepatitis B virus infection. In those with both HIV/AIDS and hepatitis B virus antiretroviral medication should also be used. Entecavir is taken by mouth as a tablet or solution.
Nucleoside analogues are structural analogues of a nucleoside, which normally contain a nucleobase and a sugar. Nucleotide analogues are analogues of a nucleotide, which normally has one to three phosphates linked to a nucleoside. Both types of compounds can deviate from what they mimick in a number of ways, as changes can be made to any of the constituent parts. They are related to nucleic acid analogues.
Dennis Liotta is a chemistry professor at Emory University in Atlanta, Georgia, United States. He is noted for his work on the development of antiviral drugs.
Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo and Tyzeka. Clinical trials have shown it to be significantly more effective than lamivudine or adefovir, and less likely to cause resistance. However, HBV signature resistance mutation M204I or L180M+M204V have been associated with Telbivudine resistance.
Elvucitabine is an experimental nucleoside reverse transcriptase inhibitor (NRTI), developed by Achillion Pharmaceuticals, Inc. for the treatment of HIV infection.
Amdoxovir is a pharmaceutical drug that has undergone research for the treatment of HIV/AIDS. It acts as a nucleoside reverse transcriptase inhibitor (NRTI). The drug was discovered by Raymond F. Schinazi and C.K. Chu and developed by RFS Pharma.
Dexelvucitabine is a failed experimental agent for the management of human immunodeficiency virus infection. It is a cytidine nucleoside analog and nucleoside reverse transcriptase inhibitor. that inhibits HIV-1 replication in vitro. During phase II clinical trials there was some indication of a decreased mean viral load in patients with infected human immunodeficiency virus.
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.
Pharmasset Inc. was a pharmaceutical company based in Princeton, New Jersey in the United States. The company develops antiviral drugs for HIV, hepatitis B, and hepatitis C. In November 2011, Pharmasset was acquired by Gilead for $11.2 billion.
Tenofovir alafenamide, sold under the brand name Vemlidy, is an antiviral medication used against hepatitis B and HIV. It is used for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease and is given in combination with other medications for the prevention and treatment of HIV. It is taken by mouth.
Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken by mouth.
Simeprevir, sold under the brand name Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with include sofosbuvir or ribavirin and peginterferon-alfa. Cure rates are in 80s to 90s percent. It may be used in those who also have HIV/AIDS. It is taken by mouth once daily for typically 12 weeks.
John Charles Martin was an American billionaire businessman, and the former executive chairman (2016–2018) and CEO (1996–2016) of the American biotechnology company Gilead Sciences. He joined Gilead Sciences in 1990 as vice president for research and development. Gilead is known for developing drugs such as Atripla and commercializing Sovaldi (sofosbuvir) for the treatment of the liver virus hepatitis C. Martin is the recipient of a number of awards, including the Biotechnology Heritage Award (2017).
Bictegravir/emtricitabine/tenofovir alafenamide, sold under the brand name Biktarvy, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. One tablet, taken orally once daily, contains 50 mg bictegravir, 200 mg emtricitabine, and 25 mg tenofovir alafenamide.
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences is a research institute under the Czech Academy of Sciences (CAS). The institute centers around research in the fields of organic chemistry, biochemistry and neighboring disciplines, mostly oriented at applications in medicine and environment. It is known for its contribution in the development of key drugs against HIV and HBV. The institute also takes part in university education, supervising master's and doctoral theses.
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