Binding modes of potential anti-prion phytochemicals to PrPC structures in silico.

BACKGROUND: Prion diseases involve the conversion of a normal, cell-surface glycoprotein (PrPC) into a misfolded pathogenic form (PrPSc). One possible strategy to inhibit PrPSc formation is to stabilize the native conformation of PrPC and interfere with the conversion of PrPC to PrPSc. Many compounds have been shown to inhibit the conversion process, however, no promising drugs have been identified to cure prion diseases. OBJECTIVE: This study aims to identify potential anti-prion compounds from plant phytochemicals by integrating traditional ethnobotanical knowledge with modern in silico drug design approaches. MATERIALS AND METHODS: In the current study medicinal phytochemicals were docked with swapped and non-swapped crystal structures of PrPCin silico to identify potential anti-prions to determine their binding modes and interactions. RESULTS: Eleven new phytochemicals were identified based on their binding energies and pharmacokinetic properties. The binding sites and interactions of the known and new anti-prion compounds are similar, and differences in binding modes occur in structures with very subtle differences in side chain conformations. Binding of these compounds poses steric hindrance to neighbouring molecules. Residues shown to be associated with the inhibition of PrPC to PrPSc conversion form interactions with most of the compounds. CONCLUSION: Identified compounds might act as potent inhibitors of PrPC to PrPSc conversion. These might be attractive candidates for the development of novel anti-prion therapy although further tests in vitro cell cultures and in vivo mouse models are needed to confirm these findings.

Spontaneous bacterial peritonitis complicating extensive splanchnic vein thrombosis, a rare manifestation of essential thrombocythemia: A case report.

Key Clinical Message: Clinicians should be mindful of the rare occurrence of spontaneous bacterial peritonitis in essential thrombocythemia with extensive splanchnic vein thrombosis, especially when patients with ascites exhibit fever and abdominal pain. Abstract: Spontaneous bacterial peritonitis (SBP) complicating extensive splanchnic vein thrombosis (SVT) is a rare manifestation of essential thrombocythemia (ET). In the absence of any hypercoagulable state, JAK2 mutation can be an important risk factor for extensive SVT. Evaluation for SBP is crucial when non-cirrhotic patient exhibits fever, abdominal pain and tenderness in the background of ascites after ruling out common pathologies such as tubercular peritonitis, acute pancreatitis, Budd-Chiari syndrome and ovarian malignancy. We present a case of SBP complicating pre-hepatic portal hypertension with ascites in a 44-years-old female. On further evaluation, extensive SVT with portal cavernoma in the setting of ET was identified. She was managed with cytoreductive therapy and anticoagulation, resulting in symptom resolution.