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There are 4 ligands of the CCR5 receptor.

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There are 10.

CCL2 (MCP-1)[-], CCL3 (MIP-1a)[-], CCL4 (MIP-1β)[-], CCL5 (RANTES)[-], CCL7 (MCP-3)[-], CCL8 (MCP-2)[-], CCL11(Eotaxin)[-], CCL13 (MCP-4)[-], CCL14 (HCC-1)[-], CCL16 (HCC-4)[-]

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Maraviroc has been characterized as an inverse agonist of CCR5 (17), suggesting that Maraviroc stabilizes CCR5 in an inactive conformation.

I would say the polar opposite is true of Leronlimab. Leronlimab may be characterized as an agonist of CCR5 which serves to stabilize CCR5 in an active conformation thereby permitting communication to continue.

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Maraviroc changes the shape of the receptor so the physical dimensions of the ligand will not fit that shape (sometimes it will anyway).

There is an assumption that because with leronlimab there is no shape change ligands must be able to bind. It is a false assumption, leronimab binds to the N terminus which is a binding site for all CCR5 ligands and essential for ligand binding. If I put superglue in your door lock is your key still going to work.

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Leronlimab may be characterized as an agonist of CCR5 which serves to stabilize CCR5 in an active conformation thereby permitting communication to continue.

Using same statement on RANTES, I would say, RANTES may be characterized as an antagonist of CCR5 rendering CCR5 destabilized and in an inactive conformation thereby non conducive to intracellular communication.

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That is not what the terminology agonist/antagonist means. An agonist is a chemical or molecule that starts the action of a biological process, in this case the activation of CCR5. An antagonist is one that will stop the biological process from happening. Both maraviroc and leronlimab are antagonists.

ps. RANTES docking in CCR5 uses CCR5 to activate processes and is responsible for intracellular communication.

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CCR5 has 3 N-terminus. I would say LL binds to all 3. That is to say, I would not be surprised that for each CCR5 receptor, 3 LL may be bound to it.

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One N terminus, 3 acidic (sulfotyrosine) residues. Just think of sulfotyrosine as little pieces of velcro that aid in the binding.

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CCR5 also has ECL1 and ECL2 as binding sites for the other ligands MIP-1α, MIP-1β, and MCP-2; RANTES uses the N-terminus as does HIV.
LL does not bind to ECL1 or ECL2. Those sites remain available for communication and are not hindered when LL binds to CCR5. RANTES is left in the cold.

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Leronlimab doesn't bind to ECL2 (also known as EL2 and used by Maddon in the quote below)? But what you also fail to realize is that chemokines activate when bound to all binding sites they are set up for on that receptor. Blocking any binding site will not allow activation by that chemokine.

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while mAbs PA9 and PA14 bind to amino acids in both the N-terminus and EL2
https://www.sciencedirect.com/science/article...9502753071

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PA14 is the non-humanized version of Pro-140 now known as leronlimab.