Interaction of the new inhibitor paxlovid (PF-07321332) and ivermectin with the monomer of the main protease SARS-CoV-2: A volumetric study based on molecular dynamics, elastic networks, classical thermodynamics and SPT.

The COVID-19 pandemic has accelerated the study of drugs, most notably ivermectin and more recently Paxlovid (PF-07321332) which is in phase III clinical trials with experimental data showing covalent binding to the viral protease Mpro. Theoretical developments of catalytic site-directed docking support thermodynamically feasible non-covalent binding to Mpro. Here we show that Paxlovid binds non-covalently at regions other than the catalytic sites with energies stronger than reported and at the same binding site as the ivermectin B1a homologue, all through theoretical methodologies, including blind docking. We volumetrically characterize the non-covalent interaction of the ivermectin homologues (avermectins B1a and B1b) and Paxlovid with the mMpro monomer, through molecular dynamics and scaled particle theory (SPT). Using the fluctuation-dissipation theorem (FDT), we estimated the electric dipole moment fluctuations at the surface of each of complex involved in this study, with similar trends to that observed in the interaction volume. Using fluctuations of the intrinsic volume and the number of flexible fragments of proteins using anisotropic and Gaussian elastic networks (ANM+GNM) suggests the complexes with ivermectin are more dynamic and flexible than the unbound monomer. In contrast, the binding of Paxlovid to mMpro shows that the mMpro-PF complex is the least structurally dynamic of all the species measured in this investigation. The results support a differential molecular mechanism of the ivermectin and PF homologues in the mMpro monomer. Finally, the results showed that Paxlovid despite beingbound in different sites through covalent or non-covalent forms behaves similarly in terms of its structural flexibility and volumetric behaviour.

Miocardiopatía periparto: Informe de un caso, consideraciones diagnósticas y terapéuticas / A peripartum cardiomyopathy. A case presentation; diagnostic and therapeutic considerations

Se informa un caso de miocardiopatía periobstétrica, identificado a las 32 semanas de gestación, cuando presentó insuficiencia cardiaca congestiva. El embarazo se resolvió por vía abdominal por baja reservación fetal. Se revisan los criterios clínicos y hemodinámicos necesarios para el diagnóstico y se comentan las alternativas terapéuticas

Leiomiomatosis uterina. Informe de 77 casos / Uterine leiomyomatosis. Report of 77 cases

Se llevó a cabo un estudio retrospectivo en 77 pacientes con diagnóstico de miomatosis uterina. Se analizaron aspectos clínicos, diagnósticos, terapéuticos y anatomopatológicos. Se observó que en 79.1% de las pacientes, la edad estuvo entre 31 y 50 años; 11.5% eran nulípars. En 46.7% presentaban sangrado genital anormal. En cuanto al diagnóstico fue clínico en 59.7%; en 41.4% el tumor fue menor de 3 cm. El tipo de mioma más frecuente fue el intramural. Se efectuaron en 14.2% miomectomías; en 25.8% histerctomías vaginales, y en 55% histerectomías abdominales. Se concluye en base a los resultados, por la elección de un manejo conservador de esta patología.