Journal: Antiviral research

Article Title: Metabolic and Neurologic Consequences of Chronic Lopinavir/Ritonavir Administration to C57BL/6 mice

doi: 10.1016/j.antiviral.2010.10.006

Figure Lengend Snippet: Lopinavir/ritonavir does not affect blood glucose in mice

Article Snippet: Furthermore, triglycerides were significantly increased by the low dose of lopinavir/ritonavir that also affected cognition, while higher doses of lopinavir/ritonavir were necessary to increase cholesterol and insulin levels significantly over levels in vehicle-treated mice.

Techniques: Mouse Assay

Journal: Antiviral research

Article Title: Metabolic and Neurologic Consequences of Chronic Lopinavir/Ritonavir Administration to C57BL/6 mice

doi: 10.1016/j.antiviral.2010.10.006

Figure Lengend Snippet: Lopinavir/ritonavir decreases retroperitoneal fat mass and circulating adipokines in mice

Article Snippet: Furthermore, triglycerides were significantly increased by the low dose of lopinavir/ritonavir that also affected cognition, while higher doses of lopinavir/ritonavir were necessary to increase cholesterol and insulin levels significantly over levels in vehicle-treated mice.

Techniques: Mouse Assay

Journal: Antiviral research

Article Title: Metabolic and Neurologic Consequences of Chronic Lopinavir/Ritonavir Administration to C57BL/6 mice

doi: 10.1016/j.antiviral.2010.10.006

Figure Lengend Snippet: Lopinavir/ritonavir disrupts cognitive but not motor ability in mice

Article Snippet: Furthermore, triglycerides were significantly increased by the low dose of lopinavir/ritonavir that also affected cognition, while higher doses of lopinavir/ritonavir were necessary to increase cholesterol and insulin levels significantly over levels in vehicle-treated mice.

Techniques: Mouse Assay

Journal: Antiviral research

Article Title: Metabolic and Neurologic Consequences of Chronic Lopinavir/Ritonavir Administration to C57BL/6 mice

doi: 10.1016/j.antiviral.2010.10.006

Figure Lengend Snippet: 3.1 Effects of lopinavir/ritonavir on body weight and composition

Article Snippet: Furthermore, triglycerides were significantly increased by the low dose of lopinavir/ritonavir that also affected cognition, while higher doses of lopinavir/ritonavir were necessary to increase cholesterol and insulin levels significantly over levels in vehicle-treated mice.

Techniques:

Journal: Antiviral research

Article Title: Metabolic and Neurologic Consequences of Chronic Lopinavir/Ritonavir Administration to C57BL/6 mice

doi: 10.1016/j.antiviral.2010.10.006

Figure Lengend Snippet: Lopinavir/ritonavir significantly increases circulating serum lipids in mice

Article Snippet: Furthermore, triglycerides were significantly increased by the low dose of lopinavir/ritonavir that also affected cognition, while higher doses of lopinavir/ritonavir were necessary to increase cholesterol and insulin levels significantly over levels in vehicle-treated mice.

Techniques: Mouse Assay

Journal: Antiviral research

Article Title: Metabolic and Neurologic Consequences of Chronic Lopinavir/Ritonavir Administration to C57BL/6 mice

doi: 10.1016/j.antiviral.2010.10.006

Figure Lengend Snippet: Lopinavir/ritonavir alters body weight and body composition in mice

Article Snippet: Furthermore, triglycerides were significantly increased by the low dose of lopinavir/ritonavir that also affected cognition, while higher doses of lopinavir/ritonavir were necessary to increase cholesterol and insulin levels significantly over levels in vehicle-treated mice.

Techniques: Mouse Assay

Journal: Journal of Clinical Investigation

Article Title: The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling

doi: 10.1172/JCI200415797

Figure Lengend Snippet: Ritonavir inhibits RANKL-induced NF-κB activation. ( A ) Bone marrow macrophages pretreated with ritonavir (20 μg/ml) or vehicle for 1 hour were stimulated with RANKL for the indicated time points, and protein lysates were prepared for IκBα immunoblot. Ritonavir pretreatment impairs RANKL-induced degradation of IκBα. ( B ) Bone marrow macrophages pretreated with ritonavir (20 μg/ml) for the indicated time were stimulated with RANKL for 15 minutes and evaluated for NF-κB activation. Ritonavir inhibits NF-κB activation as assessed by EMSA after 1 hour and after 18 hours of pretreatment (Pretx). Numbers below lanes indicate relative band intensity. ( C ) Cell lysates prepared as in A and immunoblotted for phospho-IκBα (p-IκBα) and IκBα reveal similar levels of phospho-IκBα intensity, irrespective of ritonavir pretreatment, despite the failure of ritonavir pretreatment to decrease total IκBα levels. β-Actin immunoblots confirm similar amounts of cell extracts were analyzed.

Article Snippet: Ritonavir and indinavir were from Abbott Laboratories (Abbott Park, Illinois, USA) and Merck & Co. Inc. (West Point, Pennsylvania, USA), respectively.

Techniques: Activation Assay, Western Blot

Journal: Journal of Clinical Investigation

Article Title: The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling

doi: 10.1172/JCI200415797

Figure Lengend Snippet: RANKL-induced recruitment of c-Src and TRAF6 to lipid raft component is inhibited by ritonavir treatment. Preosteoclasts generated after 3 days of culture with RANKL and M-CSF were starved for 3 hours, followed by pretreatment with either vehicle or ritonavir (1 hour). Cells were then stimulated with RANKL for 5 minutes, followed by lipid raft isolation. Note the continued recruitment of TRAF2 to lipid rafts with ritonavir treatment, indicating that the inhibition is specific to TRAF6 and c-Src.

Article Snippet: Ritonavir and indinavir were from Abbott Laboratories (Abbott Park, Illinois, USA) and Merck & Co. Inc. (West Point, Pennsylvania, USA), respectively.

Techniques: Generated, Isolation, Inhibition

Journal: Journal of Clinical Investigation

Article Title: The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling

doi: 10.1172/JCI200415797

Figure Lengend Snippet: Introduction of PI3K-CA restores RANKL-induced phosphorylation of Akt and osteoclast actin ring formation in the presence of ritonavir. ( A ) Retroviral transduction of either vector or PI3K-CA (p110a-CA) into bone marrow macrophages was followed by 3 days of culture in selection media, M-CSF, and RANKL. After starvation (3 hours) and pretreatment (1 hour) with either vehicle or ritonavir, cells were stimulated with RANKL for 15 minutes. Immunoblots reveal restoration of RANKL-induced Akt phosphorylation when PI3K-CA is introduced. As expected, total PI3K is enhanced as a result of transduction (p110α blot). TRAF6 Western blots act as a loading control. ( B ) Percentage of osteoclasts with intact actin rings after ritonavir exposure is quantitated. ( C ) Osteoclasts, retrovirally transduced with either vector or PI3K-CA, were generated on glass coverslips. After 4 days, cells were exposed to various doses of ritonavir for 2 hours, then processed for immunofluorescence microscopy for β-actin. Dose-dependent disruption of the characteristic actin ring of the osteoclast cytoskeleton is observed in vector but not PI3K-CA–transduced cells.

Article Snippet: Ritonavir and indinavir were from Abbott Laboratories (Abbott Park, Illinois, USA) and Merck & Co. Inc. (West Point, Pennsylvania, USA), respectively.

Techniques: Transduction, Plasmid Preparation, Selection, Western Blot, Activated Clotting Time Assay, Generated, Immunofluorescence, Microscopy

Journal: Journal of Clinical Investigation

Article Title: The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling

doi: 10.1172/JCI200415797

Figure Lengend Snippet: Osteoclast function is impaired by ritonavir. ( A ) Osteoclasts, generated on whale dentine slices for 3 days by treatment with RANKL and M-CSF, were exposed to control medium, ritonavir (10 μg/ml), or indinavir (10 μg/ml) for an additional 2 days. TRAP-stained dentine slices show no change in osteoclast number with exposure to PIs (top panels). Following cell removal, Coomassie blue staining of dentine slices show decreased bone pits with ritonavir treatment (bottom panels). Magnification, ×100. ( B ) Ritonavir, but not indinavir, decreases pit number (per 0.36 mm 2 ), percentage of pit area, and pit depth (in micrometers) by half (each P

Article Snippet: Ritonavir and indinavir were from Abbott Laboratories (Abbott Park, Illinois, USA) and Merck & Co. Inc. (West Point, Pennsylvania, USA), respectively.

Techniques: Generated, Staining

Journal: Journal of Clinical Investigation

Article Title: The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling

doi: 10.1172/JCI200415797

Figure Lengend Snippet: Ritonavir blocks PTH-induced osteoclast formation in vivo. ( A ) Osteoclast number was determined from TRAP-stained histologic sections of calvariae from mice stimulated with PTH or vehicle and intraperitoneally injected with ritonavir or vehicle. Ritonavir abrogates the osteoclast increase stimulated by PTH ( n = 3 mice per group; P

Article Snippet: Ritonavir and indinavir were from Abbott Laboratories (Abbott Park, Illinois, USA) and Merck & Co. Inc. (West Point, Pennsylvania, USA), respectively.

Techniques: In Vivo, Staining, Mouse Assay, Injection

Journal: Journal of Clinical Investigation

Article Title: The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling

doi: 10.1172/JCI200415797

Figure Lengend Snippet: Ritonavir inhibits RANKL-induced Akt activation. ( A ) RAW 264.7 cells pretreated with ritonavir (2 μg/ml) for 1 hour and stimulated with RANKL (+RANKL) for the indicated time points. Phospho-Akt (p-Akt), total Akt (Akt), and phospho-FKHR (p-FKHR) immunoblots were performed on cell extracts. Immunoblots reveal impaired Akt and FKHR phosphorylation with ritonavir pretreatment. ( B ) Osteoclasts were stimulated with either RANKL or M-CSF for the indicated time points, and cell extracts were immunoblotted for Akt activation. Ritonavir inhibits only RANKL-induced Akt activation but not that stimulated by M-CSF. Total Akt immunoblots confirm that similar amounts of cell extracts were analyzed. +V, vehicle pretreatment; +R, ritonavir pretreatment.

Article Snippet: Ritonavir and indinavir were from Abbott Laboratories (Abbott Park, Illinois, USA) and Merck & Co. Inc. (West Point, Pennsylvania, USA), respectively.

Techniques: Activation Assay, Western Blot

Journal: Journal of Clinical Investigation

Article Title: The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling

doi: 10.1172/JCI200415797

Figure Lengend Snippet: Osteoclastogenesis is impaired by ritonavir but not indinavir. ( A ) Osteoclasts were generated from bone marrow macrophages stimulated with RANKL and M-CSF for 4 days in the presence of the indicated doses of ritonavir or indinavir. TRAP solution assay quantitation of osteoclast formation shows that the IC 50 for ritonavir is near 10 μg/ml. In contrast, cultures exposed to indinavir show no inhibition or enhancement of osteoclast formation. ( B ) Representative fields of TRAP-stained osteoclasts in the presence of control medium, indinavir (10 μg/ml), and ritonavir (10 μg/ml). Magnification, ×100. ( C ) Ritonavir dose dependently suppresses osteoclast gene markers determined by RT-PCR analysis of osteoclasts on day 4 culture.

Article Snippet: Ritonavir and indinavir were from Abbott Laboratories (Abbott Park, Illinois, USA) and Merck & Co. Inc. (West Point, Pennsylvania, USA), respectively.

Techniques: Generated, Quantitation Assay, Inhibition, Staining, Reverse Transcription Polymerase Chain Reaction

Journal: The Korean Journal of Internal Medicine

Article Title: In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses

doi: 10.3904/kjim.2020.157

Figure Lengend Snippet: Changes in viral loads in cell culture supernatant in response to different antiviral treatments. Groups are defined as follows: no treatment, hydroxychloroquine (HCQ) base 1 μg/mL (expected plasma steady-state concentration of HCQ sulfate 400 mg once daily), HCQ base 2 μg/mL (expected plasma steady-state concentration of HCQ sulfate 800 mg once daily), lopinavir/ritonavir 7.0/1.75 μg/mL (expected plasma steady-state concentration of lopinavir/ritonavir 400/100 mg twice daily), and combinations of lopinavir/ritonavir 7.0/1.75 μg/mL with HCQ base 1 or 2 μg/mL. a Denotes p

Article Snippet: Supplementary MaterialsRepresentative cytopathic effects of Vero cells after 48 hours of the inoculation of severe acute respiratory syndrome coronavirus 2 according to different antiviral treatment. (A) A 1 μg/mL of hydroxychloroquine (HCQ) base (expected from HCQ sulfate 400 mg daily), (B) 7.0/1.75 μg/mL of lopinavir/ritonavir (expected from 400/100 mg twice daily) plus 1 μg/mL of HCQ base, and (C) 7.0/1.75 μg/mL of lopinavir/ritonavir plus 2 μg/mL of HCQ base (expected from HCQ sulfate 800 mg daily).

Techniques: Cell Culture, Concentration Assay

Journal: The Korean Journal of Internal Medicine

Article Title: In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses

doi: 10.3904/kjim.2020.157

Figure Lengend Snippet: Effect of different antiviral treatments on the cytopathic effects of Vero cells 48 hours after inoculation with severe acute respiratory syndrome coronavirus 2. (A) Control, (B) no antiviral treatment, (C) 2 μg/mL of hydroxychloroquine (expected plasma steady-state concentration of hydroxychloroquine sulfate 800 mg once daily), and (D) 7.0/1.75 μg/mL of lopinavir/ritonavir (expected plasma steady-state concentration of lopinavir/ritonavir 400/100 mg twice daily).

Article Snippet: Supplementary MaterialsRepresentative cytopathic effects of Vero cells after 48 hours of the inoculation of severe acute respiratory syndrome coronavirus 2 according to different antiviral treatment. (A) A 1 μg/mL of hydroxychloroquine (HCQ) base (expected from HCQ sulfate 400 mg daily), (B) 7.0/1.75 μg/mL of lopinavir/ritonavir (expected from 400/100 mg twice daily) plus 1 μg/mL of HCQ base, and (C) 7.0/1.75 μg/mL of lopinavir/ritonavir plus 2 μg/mL of HCQ base (expected from HCQ sulfate 800 mg daily).

Techniques: Concentration Assay