Benhur Lee, inventor of Lj001, was asked how this antibody compares with other broad spectrum anti-virals (specifically anti-ps). Dr. Lee replied:
Re: Could we possibily have another "Holy Grail" in the making?
« Reply #8 on: February 04, 2010, 02:15:57 am »
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Hey guys,
So I corresponded with Dr. Benhur Lee, lead UCLA researcher of this project, and asked him some questions about Lj001. He was generous enough to reply, and he gave me some more expanded information on this. He also gave me permission to share with everyone here what he replied to me. His only request (as seen in his reply) is that no part of his response is taken out of context. That's why rather than paraphrase his reply I'll just copy it to keep it accurate. The parts in italics were the questions I posed to him in my original email:
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Dear J.
Thank you for your interest. I am pleasantly surprised to see how much attention/discussion it has engendered in forums.poz.com. Clearly, there are informed readers that have asked very germane questions.
Let me try and answer your questions the best I can . . . but I apologize for being a bit nebulous because we have since found out the exact mechanism (which is entirely novel and unexpected) but the patent on this mechanistic discovery has not been filed so I have been advised not to talk specifically about it in public.
(1) what effect can this compound have on HIV-infected cells? What is your hypothesis regarding any benefit to those already infected with the virus, as opposed to the prevention of initial infection?
The compound binds specifically [to] lipid membranes, both cellular and viral membranes. All I can say now is the compound needs to be "activated" in order to effectuate its damaging effects on membrane components (such as phospholipids and cholesterol). The damage is not specific to viral membranes per se (like HIV's) but the reason why it is antiviral at the concentration used is that any damage it does to metabolically active cellular membranes can be repaired by the cell's biogenic repair machinery whereas viral membranes are static and cannot recover from the damage.
That being said, since we know now how to activate the compound (I wish I can be more specific, but I hope you understand the restrictions I am under) we are currently working on strategies to specifically target the activation of the compound on viruses or on virally infected cells. Your question of whether we can specifically target and destroy virally infected cells is something we are exploring by targeted activation of the compound.
(2) Do you know if LJ001 also interacts with aminophospholipid, and could cause the destruction of the infected cell?
No, it does not target a specific aminophospholipid or externalized PS on infected cells as suggested by some of the other bloggers. It does target other features of specific phospholipids and most likely, membrane cholesterol as well. Injection of the compound into mice once a day for 7 days resulted in no toxicity monitored by complete chemistry panels and CBC EXCEPT for a slight elevantion in trigylcerides and cholesterol (also consistent with its lipid targeting mechanism).
In summary, we are working hard on getting out the next paper on our second generation compounds where we could better explain its molecular mechanism of action. Unfortunately, science does not progress as fast as we want to . . . it took us 4 years just to get to this point from our initial discovery of the compound--it is difficult to convince scientists when you propose a paradigm shift of how an antiviral should work.
You may feel free to post some or all of my comments on the forum, please just don't take any of my comments out of context.
Best regards,
