C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors.

Maturation inhibitors (MIs) block HIV-1 maturation by preventing the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a first-in-class MI, displayed sub-optimal efficacy in clinical trials due to presence of SP1:V7A polymorphism in the Gag protein.This polymorphism is inherently present in HIV-1 subtype C and conferred resistance to BVM.

Fullerene (C & C)-Meso-Tris-4-Carboxyphenyl Porphyrin Dyads Inhibit Entry of Wild-Type and Drug-Resistant HIV-1 Clades B and C.

The biological applications of noncationic porphyrin-fullerene (P-F) dyads as anti-HIV agents have been limited despite the established use of several cationic P-F dyads as anti-cancer photodynamic therapy (PDT) agents. This article explores the potential of amphiphilic non-cationic porphyrin-fullerene dyads as HIV-1 inhibitors under both PDT (light-treated) and non-PDT (dark) conditions. The amphiphilic P-F dyads, PBC and PBC, demonstrated enhanced efficacy in inhibiting the entry and production of HIV-1 (subtypes B and C).

MALAT1 is important for facilitating HIV-1 latency reversal in latently infected monocytes.

Long non-coding RNAs (lncRNAs) are long RNA transcripts with length >200 nucleotides that do not encode proteins. They play a crucial role in regulating HIV-1 infection, yet their involvement in myeloid cells remains underexplored. Myeloid cells are susceptible to HIV infection and contribute substantially to the latent HIV reservoir.

Transcriptomic study reveals alteration in the expression of long non-coding RNAs (lncRNAs) during reversal of HIV-1 latency in monocytic cell line.

Background: The presence of latent HIV reservoirs continues to be the biggest obstacle to achieving an HIV cure. Thus, long non-coding RNAs (lncRNAs) may serve as the preferred targets for HIV latency reversal. The goal of the study was to identify prospective lncRNAs for subsequent in vitro molecular and functional characterization.

Porphyrins with combinations of 4-carboxyphenyl and 4-hydroxyphenyl substituents in meso-positions as anti-HIV-1 agents.

A series of 4-carboxyphenyl/4-hydroxyphenyl meso-substituted porphyrins were synthesized, purified, and characterized. The compounds exhibited anti-HIV-1 activities, in vitro, under both non-photodynamic (non-PDT) and photodynamic (PDT) conditions. Specifically, the porphyrins inhibited HIV-1 virus entry, with c-PB(OH) and PB(OH) showing significant anti-HIV-1 activity.

Construction of a HIV-1 subtype C 3D model using homology modeling and in-silico docking, molecular dynamics simulation, and MM-GBSA calculation of second-generation HIV-1 maturation inhibitor(s).

Maturation inhibitors (MIs) efficiently block HIV-1 maturation by inhibiting the cleavage of the capsid protein and spacer peptide 1 (CA-SP1) leading to the production of immature and non-infectious virus particles. We have previously reported that second-generation MIs were more potent than bevirimat (BVM) against HIV-1 subtype C. In-silico studies on interaction of with BVM and their analogs have been limited to HIV-1 subtype B(5I4T) due to lack of an available 3D structure for HIV-1 subtype C virus.

Edelfosine reactivates latent HIV-1 reservoirs in myeloid cells through activation of NF-κB and AP1 pathway.

The persistence of latent HIV-1 reservoirs in cells presents a formidable challenge towards a complete HIV cure. Edelfosine is an FDA-approved investigational, anti-neoplastic drug. In this study, we aimed to investigate its role as a HIV-1 Latency Reversal Agent (LRA) using latency model cell lines.

Construction and characterization of a full-length, replication-competent and infectious enhanced green fluorescence protein-tagged HIV-1 subtype C molecular clone.

HIV-1 subtype C virus accounts for nearly 50% of the total HIV infections globally. Despite this high prevalence, our understanding of subtype C specific infections remains limited due to lack of an in vitro model system. This is the first report of construction and characterization of a full-length and infectious EGFP-tagged HIV-1 subtype C molecular clone.

Two cationic meso-thiophenium porphyrins and their zinc-complexes as anti-HIV-1 and antibacterial agents under non-photodynamic therapy (PDT) conditions.

The anti-HIV-1 and antimicrobial activities of novel cationic meso-thiophenium porphyrins and their zinc-complex are reported under in vitro non-photodynamic (PDT) conditions. While all the cationic porphyrins led to the inhibition of de novo virus infection, the Zn(II)-complexes of T(OH)M (AB-type) and T(OH)M (AB-type) displayed potent inhibition of HIV-1 entry with T(OH)MZn displaying maximal anti-HIV activity. The Zinc complex of both the thiophenium porphyrins T(OH)M and T(OH)M also depicted antibacterial activities against Escherichia coli (ATCC 25922) and more prominently against Staphylococcus aureus (ATCC 25923).

Buccal swabs as non-invasive specimens for detection of severe acute respiratory syndrome coronavirus-2.

Introduction: The current gold standard for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA involves subjecting nasopharyngeal or oropharyngeal swabs to reverse transcription quantitative PCR (RT-qPCR). However, both sample types need to be collected by trained professionals. Using self-collected buccal swabs as an alternative could simplify and accelerate diagnosis of coronavirus disease 2019 (COVID-19).

A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors.

Background: Maturation inhibitors (MIs) potently block HIV-1 maturation by inhibiting the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a highly efficacious first-in-class MI against HIV-1 subtype B isolates, elicited sub-optimal efficacy in clinical trials due to polymorphisms in the CA-SP1 region of the Gag protein (SP1:V7A). HIV-1 subtype C inherently contains this polymorphism thus conferring BVM resistance, however it displayed sensitivity to second generation BVM analogs.

miR-150-mediated increase in glucose uptake in HIV-infected cells.

Replication of HIV-1 inside host cells is dependent on both viral and host factors. MicroRNAs are small noncoding RNAs that regulate protein synthesis. MicroRNAs may control viral replication either by directly targeting the viral genome or indirectly through cellular proteins that are required during the viral lifecycle.

Identification of MHC Class I bound peptides of Francisella tularensis Live Vaccine Strain using mass spectrometry.

Tularemia, a zoonosis generally prevalent in the northern half of the globe, is caused by Francisella tularensis. Among various Francisella tularensis species, subspecies tularensis is the most pathogenic to humans causing the infection through an airborne route, abrasions in the skin, and contact with infected animals. At present no approved vaccine exists for this intracellular pathogen.

G protein-coupled and ATP-sensitive inwardly rectifying potassium ion channels are essential for HIV entry.

The high genetic diversity of Human Immunodeficiency virus (HIV), has hindered the development of effective vaccines or antiviral drugs against it. Hence, there is a continuous need for identification of new antiviral targets. HIV exploits specific host proteins also known as HIV-dependency factors during its replication inside the cell.

Resistance to Second-Generation HIV-1 Maturation Inhibitors.

A betulinic acid-based compound, bevirimat (BVM), inhibits HIV-1 maturation by blocking a late step in protease-mediated Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA. Previous studies showed that mutations conferring resistance to BVM cluster around the CA-SP1 cleavage site. Single amino acid polymorphisms in the SP1 region of Gag and the C terminus of CA reduced HIV-1 susceptibility to BVM, leading to the discontinuation of BVM's clinical development.

Role of APOBEC3 proteins in proteasome inhibitor-mediated reactivation of latent HIV-1 viruses.

Proteasome inhibitors (PIs) have been identified as an emerging class of HIV-1 latency-reversing agents (LRAs). These inhibitors can reactivate latent HIV-1 to produce non-infectious viruses. The mechanism underlying reduced infectivity of reactivated viruses is unknown.

Human APOBEC3B interacts with the heterogenous nuclear ribonucleoprotein A3 in cancer cells.

Human APOBEC3B (A3B), like other APOBEC3 members, is a cytosine deaminase which causes hypermutation of single stranded genome. Recent studies have shown that A3B is predominantly elevated in multiple cancer tissues and cell lines such as the bladder, cervix, lung, head and neck, and breast. Upregulation and activation of A3B in developing tumors can cause an unexpected cluster of mutations which promote cancer development and progression.

Insights into the activity of maturation inhibitor PF-46396 on HIV-1 clade C.

HIV maturation inhibitors are an emerging class of anti-retroviral compounds that inhibit the viral protease-mediated cleavage of the Gag, CA-SP1 (capsid-spacer peptide 1) peptide to mature CA. The first-in-class maturation inhibitor bevirimat (BVM) displayed potent activity against HIV-1 clade B but was ineffective against other HIV-1 clades including clade C. Another pyridone-based maturation inhibitor, PF-46396 displayed potent activity against HIV-1 clade B.

Immunoproteomic Analysis of Antibody Response of Rabbit Host Against Heat-Killed Francisella tularensis Live Vaccine Strain.

Francisella tularensis, the causative agent of tularemia, has attained the status of one of the high priority agents that could be used in the act of bioterrorism. Currently, there is no licensed vaccine for this highly infectious intracellular pathogen. Being a listed 'Category A' agent of the U.

Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells.

Mitochondrial Dysfunction has been implicated in multiple human diseases, including cancer. Among all cancer, lung cancer is the most common type of cancer worldwide with low survival rates. Mammals possess multiple subunits of the mitochondrial enzyme Cytochrome C oxidase (COX).

Identification of potent maturation inhibitors against HIV-1 clade C.

Antiretroviral therapy has led to a profound improvement in the clinical care of HIV-infected patients. However, drug tolerability and the evolution of drug resistance have limited treatment options for many patients. Maturation inhibitors are a new class of antiretroviral agents for treatment of HIV-1.