crofelemer
Crofelemer previously known as SP-303 is a large proanthocyanidin oligomer isolated from the bark latex of the plant Croton lechleri Müll. Arg. [41].
Initial studies have demonstrated the immense antiviral activity of crofelemer against a gamma of DNA and RNA viruses such as respiratory syncytial virus, influenza A virus, parainfluenza virus, herpesvirus types 1 and 2, and hepatitis A and B viruses. The antiviral mechanism implies the direct interaction of crofelemer to components of the viral envelope, blocking both the viral attachment and the cell invasion [41].
More recently, crofelemer is used as a first-in-class antidiarrheal medication, and its efficacy has been investigated in vivo assays [42] and in patients with HIV-associated diarrhea, diarrhea of various infectious etiologies, as well as diarrhea-predominant irritable bowel syndrome [43].
Crofelemer was recently approved by the FDA to treat diarrhea in HIV/AIDS patients on antiretroviral therapy [44].
The mechanism of action as antidiarrheal of this proanthocyanidin oligomer consists in the dual inhibitory action on two structurally unrelated prosecretory intestinal Cl− channels, which are responsible for chloride secretion and subsequent luminal hydration. The first target is an extracellular site of the cystic fibrosis transmembrane regulator (CFTR) Cl− channel (∼60%, IC50 ∼ 7 μM), which produces a voltage-independent block with stabilization of the channel closed state. The second target is the intestinal calcium-activated Cl− channel (CaCC) by a voltage-independent inhibition mechanism (>90%, IC50 ∼ 6.5 μM) [45].
Initial studies have demonstrated the immense antiviral activity of crofelemer against a gamma of DNA and RNA viruses such as respiratory syncytial virus, influenza A virus, parainfluenza virus, herpesvirus types 1 and 2, and hepatitis A and B viruses. The antiviral mechanism implies the direct interaction of crofelemer to components of the viral envelope, blocking both the viral attachment and the cell invasion [41].
More recently, crofelemer is used as a first-in-class antidiarrheal medication, and its efficacy has been investigated in vivo assays [42] and in patients with HIV-associated diarrhea, diarrhea of various infectious etiologies, as well as diarrhea-predominant irritable bowel syndrome [43].
Crofelemer was recently approved by the FDA to treat diarrhea in HIV/AIDS patients on antiretroviral therapy [44].
The mechanism of action as antidiarrheal of this proanthocyanidin oligomer consists in the dual inhibitory action on two structurally unrelated prosecretory intestinal Cl− channels, which are responsible for chloride secretion and subsequent luminal hydration. The first target is an extracellular site of the cystic fibrosis transmembrane regulator (CFTR) Cl− channel (∼60%, IC50 ∼ 7 μM), which produces a voltage-independent block with stabilization of the channel closed state. The second target is the intestinal calcium-activated Cl− channel (CaCC) by a voltage-independent inhibition mechanism (>90%, IC50 ∼ 6.5 μM) [45].
