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Scientists crack 20-year Aids puzzle that could revolutionise latest HIV medicines
By Daily Mail Reporter
Last updated at 3:26 PM on 01st February 2010
Scientists say they have solved a crucial puzzle about the Aids virus after 20 years of research and that their findings could lead to better treatments for HIV.
British and U.S. researchers said they have grown a crystal that enabled them to see the structure of an enzyme called integrase. The enzyme is found in retroviruses like HIV and is a target for some of the newest HIV medicines.
It took more than 40,000 trials for them to come up with one a crystal of sufficiently high quality to allow them to see the three-dimensional structure.
Scientists performed more than 40,000 trials before they came up with a high-quality crystal of enzyme integrase. It is found in viruses like HIV (right)
'Despite initially painstakingly slow progress and very many failed attempts, we did not give up and our effort was finally rewarded,' said co-researcher Peter Cherepanov of Imperial College London.
Scientists from Imperial and Harvard university said that having the integrase structure means researchers can begin fully to understand how integrase inhibitor drugs work, how they might be improved, and how to stop HIV developing resistance to them.
Jason Warriner, Clinical Director for Terrence Higgins Trust, said: 'This is a step in the right direction. All of these things add to our knowledge, and hopefully this will lead to new and better treatments, but we're still a long way off the final answer.
'The only way we will get there is by sustained investment in HIV research.'
When the human immunodeficiency virus (HIV) infects someone, it uses the integrase enzyme to paste a copy of its genetic information into their DNA.
Some new drugs for HIV - like Isentress from Merck & Co - work by blocking integrase, but scientists are not clear exactly how they work or how to improve them.
The only way to find out was to obtain high-quality crystals - a project that had defeated scientists for many years.
'We went back to square one and started by looking for a better model of HIV integrase which could be more amenable for crystallization,' Cherepanov said.
The researchers grew a crystal using a version of integrase borrowed from another retrovirus very similar to its HIV counterpart.
They tested the Merck and experimental Gilead drugs on the crystals, and were able to see for the first time how the medicines bind to, and block, integrase.
An estimated 63,500 adults aged over 15 were living with HIV in the UK by the end of 2005. Of these, one third did not know they were infected.
Worldwide almost 60 million people have been infected with HIV and 25 million have died of HIV-related causes since the beginning of the AIDS epidemic. There is no cure and no vaccine, although drug cocktails can keep patients healthy.
United Nations data for 2008 show that 33.4 million people had HIV and 2 million people died of AIDS. The worst-affected region is sub-Saharan Africa, accounting for 67 percent of all people living with HIV.
The study was published in the Nature journal yesterday.
How HIV and Aids developed
Ronald Reagan, pictured here in 1984, did not mention Aids publicly until 1986. He apologised for neglecting the epidemic in 1990
1884-1924: HIV transfers to humans from chimps in Africa
1966: HIV reaches Haiti
Mid 1970s: Aids enters America
1981: First official cases are diagnosed in the U.S. among five gay men
1982: The name 'Aids' is created. Illness is reported in several European countries
Terry Higgins dies at St Thomas' Hospital in the UK. The Terry Higgins Trust is set up
1983: French scientists find the virus HIV. Aids is reported among non-drug using women and children
1985: An HIV test is licensed for screening blood supplies
1986: President Reagan mentions Aids in public for the first time
The World Health Organisation (WHO) launches its global AIDS strategy
1987: AZT is the first drug approved for treating AIDS
1988: Health ministers meet to discuss AIDS and establish World Aid's Day
1990: Around eight million people are living with Aids
Freddie Mercury, who died at the age of 45, was a high profile victim of Aids
1991: Freddie Mercury, lead singer of Queen, dies of an Aids-related illness
1993: AZT is shown to be of no benefit to those in the early stages of HIV infection
1994: AZT is shown to reduce the risk of mother to child transmission of HIV
1995-6: Combination antiretroviral treatment is shown to be highly effective against HIV
1997: Around 22million people living with Aids
Aids deaths begin to decline in developed countries, due to the new drugs. In developing countries only a minority can access drugs
2001: UK government launches the first national strategy for sexual health and HIV
2002: The Global Fund is established to boost the response to AIDS, TB and malaria.
Globally HIV is leading cause of death of those aged 15-59
Aids drugs become more affordable for developing countries.
2003: The first Aids vaccine candidate to undergo a major trial is found to be ineffective.
T-20 (Fuzeon), the first in a new class of anti-HIV drugs called fusion inhibitors is licensed for use in advanced HIV in Europe and the USA
2004: THT opens an HIV testing clinic in London that offers test results in one hour
Truvada, a once-daily combination tablet containing two anti-HIV drugs, is licensed in the EU
The FDA in the U.S approves a salive-based Aids test. Results within 20 minutes are over 99% accurate. Introduced in UK in 2009
2006: Circumcision is shown to reduce HIV infection among heterosexual men.
2007: Another major HIV vaccine trial is halted after preliminary results show no benefit.
First one pill a day HIV medication Atripla is approved by EU
2008: Around 33million people are living with Aids
2009: Reports of a German HIV-positive man having his HIV 'cured' after receiving a bone marrow transplant from a donor with a genetic mutation that appears to protect against HIV.
http://www.dailymail.co.uk/health/a...IDS-puzzle-40-000-attempts.html#ixzz0eUvKz239
By Daily Mail Reporter
Last updated at 3:26 PM on 01st February 2010
Scientists say they have solved a crucial puzzle about the Aids virus after 20 years of research and that their findings could lead to better treatments for HIV.
British and U.S. researchers said they have grown a crystal that enabled them to see the structure of an enzyme called integrase. The enzyme is found in retroviruses like HIV and is a target for some of the newest HIV medicines.
It took more than 40,000 trials for them to come up with one a crystal of sufficiently high quality to allow them to see the three-dimensional structure.
Scientists performed more than 40,000 trials before they came up with a high-quality crystal of enzyme integrase. It is found in viruses like HIV (right)
'Despite initially painstakingly slow progress and very many failed attempts, we did not give up and our effort was finally rewarded,' said co-researcher Peter Cherepanov of Imperial College London.
Scientists from Imperial and Harvard university said that having the integrase structure means researchers can begin fully to understand how integrase inhibitor drugs work, how they might be improved, and how to stop HIV developing resistance to them.
Jason Warriner, Clinical Director for Terrence Higgins Trust, said: 'This is a step in the right direction. All of these things add to our knowledge, and hopefully this will lead to new and better treatments, but we're still a long way off the final answer.
'The only way we will get there is by sustained investment in HIV research.'
When the human immunodeficiency virus (HIV) infects someone, it uses the integrase enzyme to paste a copy of its genetic information into their DNA.
Some new drugs for HIV - like Isentress from Merck & Co - work by blocking integrase, but scientists are not clear exactly how they work or how to improve them.
The only way to find out was to obtain high-quality crystals - a project that had defeated scientists for many years.
'We went back to square one and started by looking for a better model of HIV integrase which could be more amenable for crystallization,' Cherepanov said.
The researchers grew a crystal using a version of integrase borrowed from another retrovirus very similar to its HIV counterpart.
They tested the Merck and experimental Gilead drugs on the crystals, and were able to see for the first time how the medicines bind to, and block, integrase.
An estimated 63,500 adults aged over 15 were living with HIV in the UK by the end of 2005. Of these, one third did not know they were infected.
Worldwide almost 60 million people have been infected with HIV and 25 million have died of HIV-related causes since the beginning of the AIDS epidemic. There is no cure and no vaccine, although drug cocktails can keep patients healthy.
United Nations data for 2008 show that 33.4 million people had HIV and 2 million people died of AIDS. The worst-affected region is sub-Saharan Africa, accounting for 67 percent of all people living with HIV.
The study was published in the Nature journal yesterday.
How HIV and Aids developed
1884-1924: HIV transfers to humans from chimps in Africa
1966: HIV reaches Haiti
Mid 1970s: Aids enters America
1981: First official cases are diagnosed in the U.S. among five gay men
1982: The name 'Aids' is created. Illness is reported in several European countries
Terry Higgins dies at St Thomas' Hospital in the UK. The Terry Higgins Trust is set up
1983: French scientists find the virus HIV. Aids is reported among non-drug using women and children
1985: An HIV test is licensed for screening blood supplies
1986: President Reagan mentions Aids in public for the first time
The World Health Organisation (WHO) launches its global AIDS strategy
1987: AZT is the first drug approved for treating AIDS
1988: Health ministers meet to discuss AIDS and establish World Aid's Day
1990: Around eight million people are living with Aids
1991: Freddie Mercury, lead singer of Queen, dies of an Aids-related illness
1993: AZT is shown to be of no benefit to those in the early stages of HIV infection
1994: AZT is shown to reduce the risk of mother to child transmission of HIV
1995-6: Combination antiretroviral treatment is shown to be highly effective against HIV
1997: Around 22million people living with Aids
Aids deaths begin to decline in developed countries, due to the new drugs. In developing countries only a minority can access drugs
2001: UK government launches the first national strategy for sexual health and HIV
2002: The Global Fund is established to boost the response to AIDS, TB and malaria.
Globally HIV is leading cause of death of those aged 15-59
Aids drugs become more affordable for developing countries.
2003: The first Aids vaccine candidate to undergo a major trial is found to be ineffective.
T-20 (Fuzeon), the first in a new class of anti-HIV drugs called fusion inhibitors is licensed for use in advanced HIV in Europe and the USA
2004: THT opens an HIV testing clinic in London that offers test results in one hour
Truvada, a once-daily combination tablet containing two anti-HIV drugs, is licensed in the EU
The FDA in the U.S approves a salive-based Aids test. Results within 20 minutes are over 99% accurate. Introduced in UK in 2009
2006: Circumcision is shown to reduce HIV infection among heterosexual men.
2007: Another major HIV vaccine trial is halted after preliminary results show no benefit.
First one pill a day HIV medication Atripla is approved by EU
2008: Around 33million people are living with Aids
2009: Reports of a German HIV-positive man having his HIV 'cured' after receiving a bone marrow transplant from a donor with a genetic mutation that appears to protect against HIV.
http://www.dailymail.co.uk/health/a...IDS-puzzle-40-000-attempts.html#ixzz0eUvKz239
