Binding kinetics of highly mutated HIV-1 subtype C protease inhibition by Lopinavir and Darunavir in the face of altered conformational dynamics.

Highly mutated HIV-1 protease (PR) compromises the efficacy of lopinavir (LPV) and darunavir (DRV) used to formulate salvage regimens in HIV/AIDS management. Here, we report the kinetics of inhibition of lopinavir (LPV) and darunavir (DRV) on highly mutated South African HIV-1 subtype C PR obtained from clinical isolates. The wild-type and mutant South African HIV-1 subtype C PR were cloned and purified.

A Review on Inflammasomes and Immune Checkpoints in Pre-Eclampsia Complicated with Tuberculosis and Human Immune Deficiency Virus.

The current review evaluates how inflammasomes and immune checkpoints are regulated in pre-eclampsia (PE) associated with tuberculosis (TB) and Human Immune Deficiency Virus (HIV). Studies indicate that inflammasomes such as (NRLP3, NEK7, and AIM2) and immune checkpoints such as (CLT4, PD-1, TIM3, and LAG-3) are dysregulated in TB- and HIV-infected individuals, and also in pre-eclamptic pregnancies, which explains why pregnant women who are either infected with TB or HIV have an increased risk of developing PE. Evidence suggests that inhibition of inflammasomes and immune checkpoints may assist in the development of novel anti-inflammatory drugs for the prevention and management of PE in patients with or without TB and HIV infection.

Craniofacial growth and function in achondroplasia: a multimodal 3D study on 15 patients.

Background: Achondroplasia is the most frequent FGFR3-related chondrodysplasia, leading to rhizomelic dwarfism, craniofacial anomalies, stenosis of the foramen magnum, and sleep apnea. Craniofacial growth and its correlation with obstructive sleep apnea syndrome has not been assessed in achondroplasia. In this study, we provide a multimodal analysis of craniofacial growth and anatomo-functional correlations between craniofacial features and the severity of obstructive sleep apnea syndrome.

Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch.

Understanding the underlying molecular interaction during a therapy switch from lopinavir (LPV) to darunavir (DRV) is essential to achieve long-term virological suppression. We investigated the kinetic and structural characteristics of multidrug-resistant South African HIV-1 subtype C protease (HIV-1 PR) during therapy switch from LPV to DRV using enzyme activity and inhibition assay, fluorescence spectroscopy, and molecular dynamic simulation. The HIV-1 protease variants were from clinical isolates with a combination of drug resistance mutations; MUT-1 (M46I, I54V, V82A, and L10F), MUT-2 (M46I, I54V, L76V, V82A, L10F, and L33F), and MUT-3 (M46I, I54V, L76V, V82A, L90M, and F53L).

Recombinant expression of HIV-1 protease using soluble fusion tags in Escherichia coli: A vital tool for functional characterization of HIV-1 protease.

HIV-1 protease expression in the laboratory is demanding because of its high cytotoxicity, making it difficult to express in bacterial expression systems such as Escherichia coli. To overcome these challenges, HIV-1 protease fusion with solubility enhancing tags helps to mitigate its cytotoxic effect and drive its expression as a soluble protein. Therefore, this review focuses on the expression of bioactive HIV-1 protease using solubility-enhancing fusion tags in Escherichia coli and summarises the characteristic features of the different common fusion tags that have been used in the expression of HIV-1 protease.