This may have been posted here before, but a great
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Posted On: 09/30/2020 10:00:55 AM
This may have been posted here before, but a great article on therapeutic benefit of CCR5 blockade.
Article demonstrates value in delaying metastasis in breast cancer, not just tumors over expressing CCR5
Also, it appears that leronlimab may have benefit in staph. aureas (MRSA). I would imagine other bacterial infections as well, but way past my knowledge base.
MRSA has estimated IS costs of $5-10B and 20,000 deaths.
This article argues that staph aureas, more than plague or small pox, likely was the selective pressure for development of CCR5 d32 mutation.
The Expanding Therapeutic Perspective of CCR5 Blockade
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770570/
Staphylococcus aureus is the cause of a large number of deadly infections worldwide, and the emergence of antibiotic-resistant S. aureus strains represents a steadily increasing global threat. The bicomponent pore-forming leukotoxin ED (LukED) is used by S. aureus to compromise the host immune system and cause deadly infectivity, and the gene for LukED is present in numerous clinically relevant S. aureusstrains (34). LukE binds to human (and mouse) CCR5 on T cells, macrophages, and dendritic cells (35); subsequently, a bicomponent octamer formed by alternate LukE and LukD monomers assembles on the surface of target cells. The pores formed by LukED ultimately lead to cell death. LukED kills CCR5+ cells in vivo in mice, and animals lacking CCR5 are protected from mortality due to S. aureus infection (35). Even though both LukE and gp120 target CCR5, they use different determinants on the receptor (36). Interestingly, CCR5 antagonism by maraviroc (a small chemical HIV-1 entry inhibitor) confers mice with resistance to lethal S. aureus infection. Maraviroc completely blocks LukED pore formation in vitro and therefore toxicity toward CCR5+ cells (35). Therefore, the use of CCR5 antagonists to counteract S. aureusinfection is an interesting example of antibacterial intervention, alternative or even complementary to antibiotics. In light of the debate on the emergence of the CCR5Δ32 mutation, the deadly effects of S. aureusinfections on humankind and LukE tropism for CCR5 might have generated the ancient selection of the CCR5Δ32 allele (35).
Article demonstrates value in delaying metastasis in breast cancer, not just tumors over expressing CCR5
Also, it appears that leronlimab may have benefit in staph. aureas (MRSA). I would imagine other bacterial infections as well, but way past my knowledge base.
MRSA has estimated IS costs of $5-10B and 20,000 deaths.
This article argues that staph aureas, more than plague or small pox, likely was the selective pressure for development of CCR5 d32 mutation.
The Expanding Therapeutic Perspective of CCR5 Blockade
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770570/
Staphylococcus aureus is the cause of a large number of deadly infections worldwide, and the emergence of antibiotic-resistant S. aureus strains represents a steadily increasing global threat. The bicomponent pore-forming leukotoxin ED (LukED) is used by S. aureus to compromise the host immune system and cause deadly infectivity, and the gene for LukED is present in numerous clinically relevant S. aureusstrains (34). LukE binds to human (and mouse) CCR5 on T cells, macrophages, and dendritic cells (35); subsequently, a bicomponent octamer formed by alternate LukE and LukD monomers assembles on the surface of target cells. The pores formed by LukED ultimately lead to cell death. LukED kills CCR5+ cells in vivo in mice, and animals lacking CCR5 are protected from mortality due to S. aureus infection (35). Even though both LukE and gp120 target CCR5, they use different determinants on the receptor (36). Interestingly, CCR5 antagonism by maraviroc (a small chemical HIV-1 entry inhibitor) confers mice with resistance to lethal S. aureus infection. Maraviroc completely blocks LukED pore formation in vitro and therefore toxicity toward CCR5+ cells (35). Therefore, the use of CCR5 antagonists to counteract S. aureusinfection is an interesting example of antibacterial intervention, alternative or even complementary to antibiotics. In light of the debate on the emergence of the CCR5Δ32 mutation, the deadly effects of S. aureusinfections on humankind and LukE tropism for CCR5 might have generated the ancient selection of the CCR5Δ32 allele (35).
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