Proteopedia - User contributions [en]

User:Garrett Asanuma

2011-07-05T16:42:52Z

Garrett Asanuma:

Holds an M.S. in Biotechnology & Bioinformatics from the California State University at Channel Islands. Received a B.S. in Pharmacology from the University of California, Santa Barbara. Currently working full time in Thousand Oaks, CA at Amgen Inc.

User:Garrett Asanuma

2011-07-05T16:42:33Z

Garrett Asanuma:

Holds an M.S. degree in Biotechnology & Bioinformatics from the California State University at Channel Islands. Received a B.S. in Pharmacology from the University of California, Santa Barbara. Currently working full time in Thousand Oaks, CA at Amgen Inc.

User talk:Garrett Asanuma

2010-02-14T16:20:58Z

Garrett Asanuma:

'''Welcome to ''Proteopedia''!''' We hope you will contribute much and well. You will probably want to watch the narrated [[Proteopedia:Video_Guide|video guide]] and use the [[Help:Contents|help pages]] for later reference. Again, welcome and have fun! [[User:Eran Hodis|Eran Hodis]] 02:24, 7 January 2010 (IST)

== Question about Copyright of 2 images ==

Hi Garrett,

I noticed that you recently uploaded two images to Proteopedia without mention of their copyright status. We have to be careful with adding images to Proteopedia that are under copyright since that is illegal. Could you take a look at the two images that you recently added: [[:Image:GAViralLifeCycle.jpg]] and [[:Image:HIV_Stats.jpg]] and find out what their copyright status is? If any of the images came from a scientific article, and the publishing journal is not "Open Access", then the figure must be removed from Proteopedia. If any of the figures came from a website, you may be able to find copyright details on that website. If, however, you have created any of these images, then of course you are free to upload them to Proteopedia. If you have any questions (also general questions about Proteopedia, unrelated to these copyright issues) I'm more than glad to help. To answer this message, edit my talk page at [[User_talk:Eran Hodis]]. Every user page has an associated talk page that can be edited to send messages to other users.

--[[User:Eran Hodis|Eran Hodis]] 15:45, 14 February 2010 (IST)

Hi Eran,

The images were created in powerpoint by myself. Let me know if you need any other information. Thanks.

File:GAViralLifeCycle.jpg

2010-02-14T04:15:11Z

Garrett Asanuma:

Retroviral Integrase

2010-02-14T04:14:58Z

Garrett Asanuma:

==Introduction==

Integrase is an essential retroviral enzyme that binds to viral DNA and inserts it into a host cell chromosome. [The reverse transcribed cDNA of human immunodeficiency virus type 1 (HIV-1) is inserted in the host cell genome in order increase pathogen fitness and virulence.]It is produced by a class of retrovirus (like HIV) and is used by the virus to incorporate its genetic material into the host cell DNA. The host cellular machinery then produces mRNA and then protein from the incorporated genetic material, thus replicating the virus. Although several integrase inhibiting drugs have been investigated, the mechanism [responsible for strand-transfer inhibition action remain unclear] of action was not clear. On February 1, 2010, a crystal structure of the PFV Intasome was published, paving the way for better retroviral treatments. [However, Hare ''et al'' (2010) determined the structural constituents of retroviral integration. Further elucidation of the complete structure of the retroviral integrase, and its application to regulate functional and enzymatic activities could potentially enable researchers to delay the progression of retroviral diseases. Moreover, study of HIV-1 integration could lead to a promising new target, and contribute to the generation pharmacophore models for antiviral therapy. ]

HIV Integrase inhibitors: Raltegravir, marketed as Isentress is currently approved as a therapeutic inhibitor of HIV integrase. It was approved on October 12, 2007.
[link below has a table of antiretroviral drugs with trade name, company, patents, and notes]

==Integrase Mechanism of Action==

[[Image:GAViralLifeCycle.jpg]]

==HIV and AIDS==

To date, more than 25 million people have died of AIDS and it is estimated that approximately 33 million people are living with HIV today.

[[Image:HIV_Stats.jpg]]

==Impact of Structure==

HIV protease and integrase structures are among the highest ranked structures that have contributed to saving many lives and added to the quality of life of many HIV-afflicted individuals. It is implemented in [[Structure-based drug design|structure-based drug design]] to develop [http://en.wikipedia.org/wiki/Protease_inhibitors protease inhibitors] and [http://en.wikipedia.org/wiki/Integrase_inhibitors integrase inhibitors], and is used as a significant component of ''highly active anti-retroviral therapy'' ([http://en.wikipedia.org/wiki/Haart HAART]).

While existing antiretroviral agents improve the quality of life as well as extending the life of many patients, it fails to eradicate the disease. Studies in integrase inhibitors show that combination with other antiretroviral drugs diminish viral adaptations, and may have the potential to be used for ''salvage therapy'' for patients who have acquired resistance to other drugs. For more, please see [[User:Eric_Martz/Molecular_Playground/HIVDrug|AIDS Before Protease Inhibitors & HIV Protease Inhibitors: A Breakthrough]].

==PFV Crystallization==

To mimic the viral DNA ends of HIV-1, Hare ''et al'' (2010) utilized soluble and fully functional prototype foamy virus (PFV) intasome preparations, obtained using recombinant PFV integrase and double-stranded oligonucleotides.

The remarkable stability of the integrase-DNA complexes were determined by observing the ''in vitro'' strand transfer reactions, which were classified into three modes of deproteination migration: (1) single concerted events: linearized target plasmid; (2) multiple concerted events: smear; (3) half-site events: open circular DNA. Further characterization of the PFV intasome also exhibited structural substantiality which implied strong protein-protein and protein-DNA interactions despite prolonged incubation under high ionic strength conditions. Comprehensive crystallization assays effected a viable crystal configuration that diffracted X-rays to 2.9 Angstroms resolution. A three-dimensional structure was ultimately determined. The asymmetric unit contained a single integrase dimer with a stably bound viral DNA molecule, and a pair of integrase dimers consociated with symmetry, which formed an oblong tetramer. The dimer interface is stabilized by intermolecular amino terminal and catalytic core domains (inner subunit-outer subunit) interactions. The overall shape of the oblong tetramer is unique albeit bearing semblances to previously reported HIV-1 integrase complexes.

==Overall Architecture & Components==

===Active Site===

==Mechanism for strand-transfer inhibition action==

==Integrase Inhibitors==

{| class="wikitable"
| '''Name''' || '''Trade name''' || '''Company''' || '''Patent''' || '''Notes'''

|-
| [http://www.isentress.com/raltegravir/isentress/consumer/index.jsp Raltegravir] || Isentress || [http://www.merck.com/ Merck & Co.] || - || also known as MK-0518. The isopropyl and methyl-oxadiazole of MK-0518 are involved in hydrophobic and stacking interactions with side chains of Pro 214 and Tyr 212 to stabilize this drug within the PFV intasome active site. This manner of drug-binding interaction causes displacement of the reactive 3' viral DNA end from the active site of PFV intasome. After binding of MK-0518 to active site, the reactive 3' hydroxyl group moves away from the active site of the PFV intasome by more than 6 Angstroms. Raltegravir was approved by the FDA on October 12, 2007, for use with other anti-HIV agents in the treatment of HIV infection in adults. It is the first integrase inhibitor approved by the FDA.
|-
| [[Elvitegravir]] || GS-9137 || [http://www.gilead.com/ Gilead Science] || - || GS-9137 interacts with Pro 214 of PFV intasome through its quinolone base and isopropyl group. In experimental stages; shares the core structure of quinolone antibiotics. Phase II studies of elvitegravir in people who are treatment experienced have been completed. Phase III studies in treatment experienced patients are ongoing. A phase II study of elvitegravir in people who have never taken antiretroviral therapy is underway. This study will also be evaluated a boosting agent in place of Norvir, currently called GS9350. Elvitegravir holds promise for HIV-positive patients who have taken other anti-HIV drugs in the past.
|-
| [[MK-2048]] || - || [http://www.merck.com/ Merck & Co.] || - || A second generation integrase inhibitor, intended to be used against HIV infection. It is superior to the first available integrase inhibitor, raltegravir, in that it inhibits the HIV enzyme integrase 4 times longer. It is being investigated for use as part of pre-exposure prophylaxis (PrEP).
|-
|}

==References==

1.Hare, Stephen; Gupta, Saumya Shree; Valkov, Eugene; Engelman, Alan & Cherepanov, Peter (2010) Retroviral intasome assembly and inhibition of DNA strand transfer. ''Nature'' 2010/01/31/online doi:10.1038/nature08784 <http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08784.html> {{STRUCTURE_3l2q | PDB=3l2q | SCENE= }}

2. http://www.isentress.com/raltegravir/isentress/consumer/index.jsp

3. deJesus, Edwin [http://www.thebody.com/content/art1352.html#ii HIV Antiretroviral Agents in Development]. The Body: The Complete HIV/AIDS Resource. March 30, 2006.

4. [http://www.aidsinfo.nih.gov AIDS Info]

==Further Reading==

* GEN News Highlights [http://www.genengnews.com/news/bnitem.aspx?name=74423430&nc=1 "Scientists Solve 3-D Crystal Structure of Retroviral Integrase Bound to Viral DNA"], [http://www.genengnews.com Genetic Engineering & Biotechnology News] February 1, 2010.

Retroviral Integrase

2010-02-14T04:13:24Z

Garrett Asanuma:

==Introduction==

Integrase is an essential retroviral enzyme that binds to viral DNA and inserts it into a host cell chromosome. [The reverse transcribed cDNA of human immunodeficiency virus type 1 (HIV-1) is inserted in the host cell genome in order increase pathogen fitness and virulence.]It is produced by a class of retrovirus (like HIV) and is used by the virus to incorporate its genetic material into the host cell DNA. The host cellular machinery then produces mRNA and then protein from the incorporated genetic material, thus replicating the virus. Although several integrase inhibiting drugs have been investigated, the mechanism [responsible for strand-transfer inhibition action remain unclear] of action was not clear. On February 1, 2010, a crystal structure of the PFV Intasome was published, paving the way for better retroviral treatments. [However, Hare ''et al'' (2010) determined the structural constituents of retroviral integration. Further elucidation of the complete structure of the retroviral integrase, and its application to regulate functional and enzymatic activities could potentially enable researchers to delay the progression of retroviral diseases. Moreover, study of HIV-1 integration could lead to a promising new target, and contribute to the generation pharmacophore models for antiviral therapy. ]

HIV Integrase inhibitors: Raltegravir, marketed as Isentress is currently approved as a therapeutic inhibitor of HIV integrase. It was approved on October 12, 2007.
[link below has a table of antiretroviral drugs with trade name, company, patents, and notes]

==Integrase Mechanism of Action==

[[Image:slide1.jpg]]

==HIV and AIDS==

To date, more than 25 million people have died of AIDS and it is estimated that approximately 33 million people are living with HIV today.

[[Image:HIV_Stats.jpg]]

==Impact of Structure==

HIV protease and integrase structures are among the highest ranked structures that have contributed to saving many lives and added to the quality of life of many HIV-afflicted individuals. It is implemented in [[Structure-based drug design|structure-based drug design]] to develop [http://en.wikipedia.org/wiki/Protease_inhibitors protease inhibitors] and [http://en.wikipedia.org/wiki/Integrase_inhibitors integrase inhibitors], and is used as a significant component of ''highly active anti-retroviral therapy'' ([http://en.wikipedia.org/wiki/Haart HAART]).

While existing antiretroviral agents improve the quality of life as well as extending the life of many patients, it fails to eradicate the disease. Studies in integrase inhibitors show that combination with other antiretroviral drugs diminish viral adaptations, and may have the potential to be used for ''salvage therapy'' for patients who have acquired resistance to other drugs. For more, please see [[User:Eric_Martz/Molecular_Playground/HIVDrug|AIDS Before Protease Inhibitors & HIV Protease Inhibitors: A Breakthrough]].

==PFV Crystallization==

To mimic the viral DNA ends of HIV-1, Hare ''et al'' (2010) utilized soluble and fully functional prototype foamy virus (PFV) intasome preparations, obtained using recombinant PFV integrase and double-stranded oligonucleotides.

The remarkable stability of the integrase-DNA complexes were determined by observing the ''in vitro'' strand transfer reactions, which were classified into three modes of deproteination migration: (1) single concerted events: linearized target plasmid; (2) multiple concerted events: smear; (3) half-site events: open circular DNA. Further characterization of the PFV intasome also exhibited structural substantiality which implied strong protein-protein and protein-DNA interactions despite prolonged incubation under high ionic strength conditions. Comprehensive crystallization assays effected a viable crystal configuration that diffracted X-rays to 2.9 Angstroms resolution. A three-dimensional structure was ultimately determined. The asymmetric unit contained a single integrase dimer with a stably bound viral DNA molecule, and a pair of integrase dimers consociated with symmetry, which formed an oblong tetramer. The dimer interface is stabilized by intermolecular amino terminal and catalytic core domains (inner subunit-outer subunit) interactions. The overall shape of the oblong tetramer is unique albeit bearing semblances to previously reported HIV-1 integrase complexes.

==Overall Architecture & Components==

===Active Site===

==Mechanism for strand-transfer inhibition action==

==Integrase Inhibitors==

{| class="wikitable"
| '''Name''' || '''Trade name''' || '''Company''' || '''Patent''' || '''Notes'''

|-
| [http://www.isentress.com/raltegravir/isentress/consumer/index.jsp Raltegravir] || Isentress || [http://www.merck.com/ Merck & Co.] || - || also known as MK-0518. Raltegravir was approved by the FDA on October 12, 2007, for use with other anti-HIV agents in the treatment of HIV infection in adults. It is the first integrase inhibitor approved by the FDA.
|-
| [[Elvitegravir]] || GS-9137 || [http://www.gilead.com/ Gilead Science] || - || in experimental stages; shares the core structure of quinolone antibiotics. Phase II studies of elvitegravir in people who are treatment experienced have been completed. Phase III studies in treatment experienced patients are ongoing. A phase II study of elvitegravir in people who have never taken antiretroviral therapy is underway. This study will also be evaluated a boosting agent in place of Norvir, currently called GS9350. Elvitegravir holds promise for HIV-positive patients who have taken other anti-HIV drugs in the past.
|-
| [[MK-2048]] || - || [http://www.merck.com/ Merck & Co.] || - || A second generation integrase inhibitor, intended to be used against HIV infection. It is superior to the first available integrase inhibitor, raltegravir, in that it inhibits the HIV enzyme integrase 4 times longer. It is being investigated for use as part of pre-exposure prophylaxis (PrEP).
|-
|}

==References==

1.Hare, Stephen; Gupta, Saumya Shree; Valkov, Eugene; Engelman, Alan & Cherepanov, Peter (2010) Retroviral intasome assembly and inhibition of DNA strand transfer. ''Nature'' 2010/01/31/online doi:10.1038/nature08784 <http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08784.html> {{STRUCTURE_3l2q | PDB=3l2q | SCENE= }}

2. http://www.isentress.com/raltegravir/isentress/consumer/index.jsp

3. deJesus, Edwin [http://www.thebody.com/content/art1352.html#ii HIV Antiretroviral Agents in Development]. The Body: The Complete HIV/AIDS Resource. March 30, 2006.

4. [http://www.aidsinfo.nih.gov AIDS Info]

==Further Reading==

* GEN News Highlights [http://www.genengnews.com/news/bnitem.aspx?name=74423430&nc=1 "Scientists Solve 3-D Crystal Structure of Retroviral Integrase Bound to Viral DNA"], [http://www.genengnews.com Genetic Engineering & Biotechnology News] February 1, 2010.

File:HIV Stats.jpg

2010-02-14T03:27:15Z

Garrett Asanuma: uploaded a new version of "Image:HIV Stats.jpg"

File:HIV Stats.jpg

2010-02-14T03:26:20Z

Garrett Asanuma: uploaded a new version of "Image:HIV Stats.jpg"

Retroviral Integrase

2010-02-14T03:24:45Z

Garrett Asanuma:

==Introduction==

Integrase is an essential retroviral enzyme that binds to viral DNA and inserts it into a host cell chromosome. [The reverse transcribed cDNA of human immunodeficiency virus type 1 (HIV-1) is inserted in the host cell genome in order increase pathogen fitness and virulence.]It is produced by a class of retrovirus (like HIV) and is used by the virus to incorporate its genetic material into the host cell DNA. The host cellular machinery then produces mRNA and then protein from the incorporated genetic material, thus replicating the virus. Although several integrase inhibiting drugs have been investigated, the mechanism [responsible for strand-transfer inhibition action remain unclear] of action was not clear. On February 1, 2010, a crystal structure of the PFV Intasome was published, paving the way for better retroviral treatments. [However, Hare ''et al'' (2010) determined the structural constituents of retroviral integration. Further elucidation of the complete structure of the retroviral integrase, and its application to regulate functional and enzymatic activities could potentially enable researchers to delay the progression of retroviral diseases. Moreover, study of HIV-1 integration could lead to a promising new target, and contribute to the generation pharmacophore models for antiviral therapy. ]

HIV Integrase inhibitors: Raltegravir, marketed as Isentress is currently approved as a therapeutic inhibitor of HIV integrase. It was approved on October 12, 2007.
[link below has a table of antiretroviral drugs with trade name, company, patents, and notes]

==HIV and AIDS==

To date, more than 25 million people have died of AIDS and it is estimated that approximately 33 million people are living with HIV today.

[[Image:HIV_Stats.jpg]]

==Impact of Structure==

HIV protease structure is among the highest ranked structures that have contributed to saving many lives and added to the quality of life of many HIV-afflicted individuals. It is implemented in [[Structure-based drug design|structure-based drug design]] to develop [http://en.wikipedia.org/wiki/Protease_inhibitor_(pharmacology) anti-retroviral protease inhibitors], and is used as a significant component of ''highly active anti-retroviral therapy'' ([http://en.wikipedia.org/wiki/Haart HAART]). While HAART improves the quality of life as well as extending the life of many patients, it fails to eradicate the disease. For more, please see [[User:Eric_Martz/Molecular_Playground/HIVDrug|AIDS Before Protease Inhibitors & HIV Protease Inhibitors: A Breakthrough]].

==PFV Crystallization==

To mimic the viral DNA ends of HIV-1, Hare ''et al'' (2010) utilized soluble and fully functional prototype foamy virus (PFV) intasome preparations, obtained using recombinant PFV integrase and double-stranded oligonucleotides.

The remarkable stability of the integrase-DNA complexes were determined by observing the ''in vitro'' strand transfer reactions, which were classified into three modes of deproteination migration: (1) single concerted events: linearized target plasmid; (2) multiple concerted events: smear; (3) half-site events: open circular DNA. Further characterization of the PFV intasome also exhibited structural substantiality which implied strong protein-protein and protein-DNA interactions despite prolonged incubation under high ionic strength conditions. Comprehensive crystallization assays effected a viable crystal configuration that diffracted X-rays to 2.9 Angstroms resolution. A three-dimensional structure was ultimately determined. The asymmetric unit contained a single integrase dimer with a stably bound viral DNA molecule, and a pair of integrase dimers consociated with symmetry, which formed an oblong tetramer. The dimer interface is stabilized by intermolecular amino terminal and catalytic core domains (inner subunit-outer subunit) interactions. The overall shape of the oblong tetramer is unique albeit bearing semblances to previously reported HIV-1 integrase complexes.

==Overall Architecture & Components==

===Active Site===

==Mechanism for strand-transfer inhibition action==

==Antiretrovirals==

{| class="wikitable"
| '''Name''' || '''Trade name''' || '''Company''' || '''Patent''' || '''Notes'''

|-
| [[Raltegravir]] || Isentress || [[Merck & Co.]] || - || also known as MK-0518. Raltegravir was approved by the FDA on October 12, 2007, for use with other anti-HIV agents in the treatment of HIV infection in adults. It is the first integrase inhibitor approved by the FDA.
|-
| [[Elvitegravir]] || GS-9137 || [[Gilead Science]] || - || in experimental stages. Phase II studies of elvitegravir in people who are treatment experienced have been completed. Phase III studies in treatment experienced patients are ongoing. A phase II study of elvitegravir in people who have never taken antiretroviral therapy is underway. This study will also be evaluated a boosting agent in place of Norvir, currently called GS9350. Elvitegravir holds promise for HIV-positive patients who have taken other anti-HIV drugs in the past.
|-

==References==

1.Hare, Stephen; Gupta, Saumya Shree; Valkov, Eugene; Engelman, Alan & Cherepanov, Peter (2010) Retroviral intasome assembly and inhibition of DNA strand transfer. ''Nature'' 2010/01/31/online doi:10.1038/nature08784 <http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08784.html> {{STRUCTURE_3l2q | PDB=3l2q | SCENE= }}

2. http://www.isentress.com/raltegravir/isentress/consumer/index.jsp

==Further Reading==

* GEN News Highlights [http://www.genengnews.com/news/bnitem.aspx?name=74423430&nc=1 "Scientists Solve 3-D Crystal Structure of Retroviral Integrase Bound to Viral DNA"], [http://www.genengnews.com Genetic Engineering & Biotechnology News] February 1, 2010.

Retroviral Integrase

2010-02-14T03:24:09Z

Garrett Asanuma:

==Introduction==

Integrase is an essential retroviral enzyme that binds to viral DNA and inserts it into a host cell chromosome. [The reverse transcribed cDNA of human immunodeficiency virus type 1 (HIV-1) is inserted in the host cell genome in order increase pathogen fitness and virulence.]It is produced by a class of retrovirus (like HIV) and is used by the virus to incorporate its genetic material into the host cell DNA. The host cellular machinery then produces mRNA and then protein from the incorporated genetic material, thus replicating the virus. Although several integrase inhibiting drugs have been investigated, the mechanism [responsible for strand-transfer inhibition action remain unclear] of action was not clear. On February 1, 2010, a crystal structure of the PFV Intasome was published, paving the way for better retroviral treatments. [However, Hare ''et al'' (2010) determined the structural constituents of retroviral integration. Further elucidation of the complete structure of the retroviral integrase, and its application to regulate functional and enzymatic activities could potentially enable researchers to delay the progression of retroviral diseases. Moreover, study of HIV-1 integration could lead to a promising new target, and contribute to the generation pharmacophore models for antiviral therapy. ]

HIV Integrase inhibitors: Raltegravir, marketed as Isentress is currently approved as a therapeutic inhibitor of HIV integrase. It was approved on October 12, 2007.
[link below has a table of antiretroviral drugs with trade name, company, patents, and notes]

==HIV and AIDS==

To date, more than 25 million people have died of AIDS and it is estimated that approximately 33 million people are living with HIV today.

[[Image:Example.jpg]]

==Impact of Structure==

HIV protease structure is among the highest ranked structures that have contributed to saving many lives and added to the quality of life of many HIV-afflicted individuals. It is implemented in [[Structure-based drug design|structure-based drug design]] to develop [http://en.wikipedia.org/wiki/Protease_inhibitor_(pharmacology) anti-retroviral protease inhibitors], and is used as a significant component of ''highly active anti-retroviral therapy'' ([http://en.wikipedia.org/wiki/Haart HAART]). While HAART improves the quality of life as well as extending the life of many patients, it fails to eradicate the disease. For more, please see [[User:Eric_Martz/Molecular_Playground/HIVDrug|AIDS Before Protease Inhibitors & HIV Protease Inhibitors: A Breakthrough]].

==PFV Crystallization==

To mimic the viral DNA ends of HIV-1, Hare ''et al'' (2010) utilized soluble and fully functional prototype foamy virus (PFV) intasome preparations, obtained using recombinant PFV integrase and double-stranded oligonucleotides.

The remarkable stability of the integrase-DNA complexes were determined by observing the ''in vitro'' strand transfer reactions, which were classified into three modes of deproteination migration: (1) single concerted events: linearized target plasmid; (2) multiple concerted events: smear; (3) half-site events: open circular DNA. Further characterization of the PFV intasome also exhibited structural substantiality which implied strong protein-protein and protein-DNA interactions despite prolonged incubation under high ionic strength conditions. Comprehensive crystallization assays effected a viable crystal configuration that diffracted X-rays to 2.9 Angstroms resolution. A three-dimensional structure was ultimately determined. The asymmetric unit contained a single integrase dimer with a stably bound viral DNA molecule, and a pair of integrase dimers consociated with symmetry, which formed an oblong tetramer. The dimer interface is stabilized by intermolecular amino terminal and catalytic core domains (inner subunit-outer subunit) interactions. The overall shape of the oblong tetramer is unique albeit bearing semblances to previously reported HIV-1 integrase complexes.

==Overall Architecture & Components==

===Active Site===

==Mechanism for strand-transfer inhibition action==

==Antiretrovirals==

{| class="wikitable"
| '''Name''' || '''Trade name''' || '''Company''' || '''Patent''' || '''Notes'''

|-
| [[Raltegravir]] || Isentress || [[Merck & Co.]] || - || also known as MK-0518. Raltegravir was approved by the FDA on October 12, 2007, for use with other anti-HIV agents in the treatment of HIV infection in adults. It is the first integrase inhibitor approved by the FDA.
|-
| [[Elvitegravir]] || GS-9137 || [[Gilead Science]] || - || in experimental stages. Phase II studies of elvitegravir in people who are treatment experienced have been completed. Phase III studies in treatment experienced patients are ongoing. A phase II study of elvitegravir in people who have never taken antiretroviral therapy is underway. This study will also be evaluated a boosting agent in place of Norvir, currently called GS9350. Elvitegravir holds promise for HIV-positive patients who have taken other anti-HIV drugs in the past.
|-

==References==

1.Hare, Stephen; Gupta, Saumya Shree; Valkov, Eugene; Engelman, Alan & Cherepanov, Peter (2010) Retroviral intasome assembly and inhibition of DNA strand transfer. ''Nature'' 2010/01/31/online doi:10.1038/nature08784 <http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08784.html> {{STRUCTURE_3l2q | PDB=3l2q | SCENE= }}

2. http://www.isentress.com/raltegravir/isentress/consumer/index.jsp

==Further Reading==

* GEN News Highlights [http://www.genengnews.com/news/bnitem.aspx?name=74423430&nc=1 "Scientists Solve 3-D Crystal Structure of Retroviral Integrase Bound to Viral DNA"], [http://www.genengnews.com Genetic Engineering & Biotechnology News] February 1, 2010.

File:HIV Stats.jpg

2010-02-14T03:20:26Z

Garrett Asanuma: uploaded a new version of "Image:HIV Stats.jpg": World wide statistics (http://www.avert.org/worldstats.htm)

File:HIV Stats.jpg

2010-02-14T03:19:27Z

Garrett Asanuma:

Retroviral Integrase

2010-02-11T22:55:31Z

Garrett Asanuma:

==Introduction==
Integrase is an essential retroviral enzyme that binds to viral DNA and inserts it into a host cell chromosome. It is produced by a class of retrovirus (like HIV) and is used by the virus to incorporate its genetic material into the host cell DNA. The host cellular machinery then produces mRNA and then protein from the incorporated genetic material, thus replicating the virus. Although several integrase inhibiting drugs have been investigated, the mechanism of action was not clear. On February 1st, 2010, a crystal structure of the PFV Intasome was published, paving the way for better retroviral treatments.

HIV Integrase inhibitors: Raltegravir, marketed as Isentress is currently approved as a therapeutic inhibitor of HIV integrase. It was approved on October 12, 2007.

==PFV Crystalization==

==Impact of Structure==

==Components==

==References==

1.Stephen Hare, Saumya Shree Gupta1, Eugene Valkov1, Alan Engelman & Peter Cherepanov. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature. 2010/01/31/online
{{STRUCTURE_3l2q | PDB=3l2q | SCENE= }}

2. http://www.isentress.com/raltegravir/isentress/consumer/index.jsp

User:Garrett Asanuma

2010-01-10T02:50:22Z

Garrett Asanuma:

A student, M.S. degree candidate in Biotechnology at California State University at Channel Islands. Holds a B.S. in Pharmacology from the University of California, Santa Barbara. Currently working full time in Thousand Oaks, CA at Amgen Inc.