Author: Vales, Anja ; Messner, Franka ; Krendl, Felix J ; Weissenbacher, Annemarie ; Riedmann, Marina ; Öfner, Dietmar ; Resch, Thomas ; Oberhuber, Rupert ; Balog, Agnes ; Maglione, Manuel ; Fodor, Margot ; Margreiter, Christian ; Schneeberger, Stefan ; Cardini, Benno ; Ulmer, Hanno

A positive crossmatch (XM+) is considered a contraindication to solid abdominal organ transplantation except liver transplantation (LT). Conflicting reports exist regarding the effects of XM+ on post-transplant outcomes. The goal of this retrospective single-center analysis is to evaluate the influence of XM+ on relevant outcome parameters such as survival, graft rejection, biliary and arterial complications. Forty-nine adult patients undergoing LT with a XM+ between 2002 and 2017 were included. XM+ LT recipients were matched 1:2 with crossmatch negative (XM-) LT recipients based on the balance of risk (BAR) score. Patient and graft survival were compared using Kaplan-Meier survival analysis and the log-rank test. Comparative analysis of clinical outcomes in XM+ and XM- groups were conducted. Patient and graft survival were similar in XM+ and XM- patients. Rejection episodes did not differ either. Recipients with a strong XM+ were more likely to develop a PCR+ CMV infection. A XM+ was not associated with a higher incidence of biliary or arterial complications. Donor age, cold ischemia time, PCR+ CMV infection and a rejection episode were associated with the occurrence of ischemic type biliary lesions. A XM+ has no effects on patient and graft survival or other relevant outcome parameters following LT.

01 Feb 2022·Saudi Journal of Biological SciencesQ3 · BIOLOGY

In silico prediction of mozenavir as a potential drug for SARS-CoV-2 infection via binding multiple drug targets

Q3 · BIOLOGY

ArticleOA

Author: Ali Kaimkhani, Zahid ; Mamidala, Estari ; Swamy, Satyanarayana ; Al-Ghanim, K A ; Mahboob, Shahid ; Abhiav, Mruthinti ; Praveen Kumar, Munipally ; Davella, Rakesh

Since the epidemic began in November 2019, no viable medicine against SARS-CoV-2 has been discovered. The typical medication discovery strategy requires several years of rigorous research and development as well as a significant financial commitment, which is not feasible in the face of the current epidemic. Through molecular docking and dynamic simulation studies, we used the FDA-approved drug mezonavir against the most important viral targets, including spike (S) glycoprotein, Transmembrane serine protease 2 (TMPRSS2), RNA-dependent RNA polymerase (RdRp), Main protease (Mpro), human angiotensin-converting enzyme 2 (ACE-2), and furin. These targets are critical for viral replication and infection propagation because they play a key role in replication/transcription and host cell recognition. Molecular docking revealed that the antiviral medication mozenavir showed a stronger affinity for SARS-CoV-2 target proteins than reference medicines in this investigation. We discovered that mozenavir increases the complex's stability and validates the molecular docking findings using molecular dynamics modeling. Furin, a target protein of COVID-19, has a greater binding affinity (-12.04 kcal/mol) than other COVID-19 target proteins, forming different hydrogen bonds and polar and hydrophobic interactions, suggesting that it might be used as an antiviral treatment against SARS-CoV-2. Overall, the present in silico results will be valuable in identifying crucial targets for subsequent experimental investigations that might help combat COVID-19 by blocking the protease furin's proteolytic activity.

01 Dec 2004·Journal of Medicinal ChemistryQ1 · MEDICINE

A Combined QM/MM Approach to Protein−Ligand Interactions: Polarization Effects of the HIV-1 Protease on Selected High Affinity Inhibitors

Q1 · MEDICINE

Article

Author: Hensen, Christian ; Gao, Jiali ; Nam, Kwangho ; Ma, Shuhua ; Hermann, Johannes C. ; Höltje, Hans-Dieter

HIV-1 protease inhibitors are one of the two widely used therapeutic agents for the treatment of HIV-infected patients. The investigation of HIV-1 protease-inhibitor interactions can provide further insight for developing new compounds that are still required due to the growing problem of drug resistance. To this end, a combined QM/MM approach was used to determine electrostatic and polarization interactions on three high affinity inhibitors, nelfinavir, mozenavir, and tipranavir. The present computational results show that explicit treatment of the polarization effect is particularly important since it can contribute as much as one-third of the total electrostatic interaction energy. Further, an amino acid decomposition analysis was applied to determine contributions of individual residues to the enzyme--inhibitor interactions. It was found that the 4-hydroxy-dihydropyrone substructure of tipranavir is especially suited for extended charge delocalization by interacting with the catalytic aspartates and isoleucines of the HIV-1 protease. The calculated electron density difference maps reaffirm and provide a means of visualizing these results.

100 Deals associated with Mozenavir mesilate

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KEGG	Wiki	ATC	Drug Bank
-	Mozenavir mesilate	-	DB02102

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Preclinical	-	Bristol Myers Squibb Co.	-
HIV Infections	Preclinical	DE	-	-
HIV Infections	Preclinical	MX	-	-
HIV Infections	Preclinical	FR	-	-
HIV Infections	Preclinical	-	Gilead Sciences, Inc.	-
HIV Infections	Preclinical	ES	-	-

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