#ritonavir

[bluesbiolab]

i love taking advantage of a hyperfixation to get motivation to study he'll yeah

[er-cryptid]

Ritonavir

NAMES -- Norvir

CLASS -- antiretroviral -- protease inhibitors

USE -- treatment of HIV infection

ACTION -- inhibits action of HIV protease -- HIV protease acts like scissors that cut the DNA chain to appropriate length -- without HIV protease, the chain is read as abnormal and terminated

[er-cryptid]

Ritonavir

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[zinderant]

Disappearing polymorphs

The topic of the most recent Veritasium video is something I'd read about before in the context of ritonavir and the disappearance of its water-soluble form, and with it, the form of the drug that was could be absorbed by the body in pill form. Spoilers for the video, I suppose, which takes a lot of detours to eventually arrive at the correct explanation: due to the slow but eventually global spread of a more stable crystal structure that 'infects' all instances of the original form, which is now impossible to manufacture. The phenomenon is called 'disappearing polymorph' (Wikipedia).

In the video they make it reasonably clear that this is a terrifying problem that could theoretically happen to any drug, and while the contamination by a more stable polymorph can be compensated for or worked around in some cases, in the case of ritonavir it was so difficult to do this that it became effectively impossible to keep that form of the drug on the market. It might even be that if you did manage to deliver ritonavir in its active form to a person who needs the drug, it would convert to an inactive form inside their body before it's had a chance to take effect.

Still, they fail to really capture the other part of why this is terrifying: the idea that microscopic bits of crystal can seed the atmosphere and stick to surfaces and clothing, resisting not only the deep cleaning procedures used in pharmaceutical manufacturing but also, for a while, the best efforts of industrial scientists to even figure out that they exist. Now, just as a result of being manufactured in a few places on the planet, the crystals have spread across the entire world. It was beyond our ability to clean them up when they were limited to the factory, and perhaps still is, so now this is an unsolveable problem on the scale of radioactive contamination of steel, but in this case, no one had to detonate any nuclear bombs to cause it.

What really terrifies me to imagine is what else might be floating around in our atmosphere, invisible and undetectable, until it suddenly creates an impossible-to-predict interaction with a chemical we might have come to rely on. We know the health effects of chemicals like PFOA only because they are present in high enough concentrations that it is possible to measure it and dedicate studies to it, but the scope of the different industrial processes that might have a global impact, even if only on a microscopic level like ritonavir, is quite literally inconceivable. We're looking at a tiny sliver of all the different compounds that have managed to become airborne since the dawn of the industrial revolution, say "those are bad for us, we should do something about those" while remaining totally unaware (not even wilfully!) of everything else in the atmosphere that could ruin our lives but doesn't. For now. I might be overreacting, but that's what really gets me about the ritonavir case.

[stelladebraa]

Effi cacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials

The continuing, randomised, multinational, phase IIB POWER 1 and 2 studies aim to evaluate effi cacy and safety of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1-infected patients. We did a pooled subgroup analysis to update results at week 48 for patients receiving the recommended dose of darunavir-ritonavir compared with those receiving other protease inhibitors (PIs).

[rbesjournal]

In Silico Analyzes for the Inhibition of HIV Protease by Ritonavir and Indinavir

Introduction: This research was conducted to investigate the molecular interaction of HIV protease inhibitor drugs using molecular docking. HIV protease is responsible for processing gag and gag-polyproteins during virion maturation. The activity of this enzyme is essential against viral infections and has beneficial therapeutic effects on HIV treatment. Materials and Methods: To meet the aim of the study, indinavir and ritonavir were selected as HIV Protease inhibitor drugs. The necessary information on molecular docking was collected through information servers, such as Drug bank and Program database (PDB). Then, molecular docking was performed using Molegro virtual docker software. In order to check the stability of the resulting complex structure and its cellular penetration, a molecular dynamics simulation was run for 50 nanoseconds using GROMACS2019.6 package and Amber99SB force force field. During the molecular dynamics simulation, root mean square deviations (RMSD), root mean square fluctuations (RMSF), the radius of gyration (RG), hydrogen bonds, and distance between ligands and complex were investigated. Results: The obtained results indicated that the RMSD of the complex of the ligands and HIV protease at the end of 50 nanoseconds had a linear slope. Hydrogen bonds decreased at beginning of simulation but they increase at the end of simulation However RG was decreased at the end of the simulation Also the RMSF was decreased at the end of simulation rather than beginning of simulation, So all the obtained results showing the stability and strength of the structure. Conclusion: Molecular docking method can indicate the relationship between structure-activity and the effectiveness of ligands on HIV protease based on the level of interaction between the ligands and the receptors.

[baby-anonymouse]

lil PSA

If any of y’all end up taking paxlovid as part of COVID treatment, don’t be super alarmed if you develop some numbness in extremities and face as this is actually a common side effect of ritonavir, one of the component meds of paxlovid.

obvs assess in comparison with other neurological symptoms you may have, like have you developed confusion, poor coordination, mood disturbances, loss of facial movement/“drooping”, etc

if no other neurological symptoms have developed in tandem with this numbness/tingling, it could very well just be a side effect of paxlovid

Im not a doctor, just someone w internet access and a familiarity w neurological disease trying to look out for people w health anxiety like myself

always still check with your doc if you have any concern!

[pharmasatyadeva]