Exploring HIV-1 Maturation: A New Frontier in Antiviral Development DOI Creative Commons
Aidan McGraw,

Grace Hillmer,

Stefania M. Medehincu

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1423 - 1423

Published: Sept. 6, 2024

HIV-1 virion maturation is an essential step in the viral replication cycle to produce infectious virus particles. Gag and Gag-Pol polyproteins are assembled at plasma membrane of virus-producer cells bud from it extracellular compartment. The newly released progeny virions initially immature noninfectious. However, once polyprotein cleaved by protease virions, mature capsid proteins assemble form fullerene core. This core, harboring two copies genomic RNA, transforms morphology into morphological transformation referred as maturation. Virion influences distribution Env glycoprotein on surface induces conformational changes necessary for subsequent interaction with CD4 receptor. Several host factors, including like cyclophilin A, metabolites such IP6, lipid rafts containing sphingomyelins, have been demonstrated influence review article delves processes recruitment, emphasis role cell factors environmental conditions. Additionally, we discuss microscopic technologies assessing development current antivirals specifically targeting this critical replication, offering long-acting therapeutic options.

Language: Английский

Update and latest advances in antiretroviral therapy DOI
Luis Menéndez‐Arias, Rafaël Delgado

Trends in Pharmacological Sciences, Journal Year: 2021, Volume and Issue: 43(1), P. 16 - 29

Published: Nov. 3, 2021

Language: Английский

Citations

145
A stable immature lattice packages IP 6 for HIV capsid maturation DOI Creative Commons
Donna L. Mallery, Alex B. Kleinpeter,

Nadine Renner

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(11)

Published: March 10, 2021

HIV immature lattice stability affects capsid maturation by altering IP 6 packaging.

Language: Английский

Citations

58
Cardiovascular Disease and Thrombosis in HIV Infection DOI Open Access
Megan Perkins, Sarah Joseph, Dirk P. Dittmer

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2022, Volume and Issue: 43(2), P. 175 - 191

Published: Dec. 1, 2022

HIV infection has transitioned from an acute, fatal disease to a chronic one managed by antiretroviral therapy. Thus, the aging population of people living with (PLWH) continues expand. results in dysregulated immune system, wherein CD4

Language: Английский

Citations

48
HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread DOI Creative Commons
С. В. Калиниченко, Dmitriy Komkov,

Dmitriy Mazurov

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(1), P. 152 - 152

Published: Jan. 14, 2022

So far, only two retroviruses, human immunodeficiency virus (HIV) (type 1 and 2) T-cell lymphotropic type (HTLV-1), have been recognized as pathogenic for humans. Both viruses mainly infect CD4+ T lymphocytes. HIV replication induces the apoptosis of CD4 lymphocytes, leading to development acquired syndrome (AIDS). After a long clinical latency period, HTLV-1 can transform with subsequent uncontrolled proliferation manifestation disease called adult leukemia (ATLL). Certain infected patients develop neurological autoimmune disorder HTLV-1-associated myelopathy, also known tropical spastic paraparesis (HAM/TSP). are transmitted between individuals via blood transfusion, tissue/organ transplantation, breastfeeding, sexual intercourse. Within host, these spread utilizing either cell-free or cell-to-cell modes transmission. In this review, we discuss mechanisms importance each mode transmission biology HIV-1 HTLV-1.

Language: Английский

Citations

43
Antiviral Activity and Mechanisms of Seaweeds Bioactive Compounds on Enveloped Viruses—A Review DOI Creative Commons
Silvia Lomartire, Ana M. M. Gonçalves

Marine Drugs, Journal Year: 2022, Volume and Issue: 20(6), P. 385 - 385

Published: June 8, 2022

In the last decades, interest in seaweed has significantly increased. Bioactive compounds from seaweed’s currently receive major attention pharmaceutical companies as they express several interesting biological activities which are beneficial for humans. The structural diversity of metabolites provides diverse expressed through mechanisms actions. This review mainly focuses on antiviral activity extracts, highlighting actions some molecules against infection caused by different types enveloped viruses: influenza, Lentivirus (HIV-1), Herpes viruses, and coronaviruses. Seaweed with properties can act trough pathways increasing host’s defense system or targeting blocking virus replication before it enters host cells. Several studies have already established large spectrum bioactive compounds. Throughout this review, medical applications analyzed, suggesting potential source formulation novel natural drugs.

Language: Английский

Citations

41
A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication DOI Open Access
Belgin Sever, Masami Otsuka, Mikako Fujita

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3659 - 3659

Published: March 25, 2024

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection a fatal illness into manageable chronic disorder. However, presence of latent reservoirs, multifaceted nature HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict efficacy current cART targeting distinct stages life cycle. Therefore, there unmet need for discovery new therapeutics that not only bypass limitations but also protect body’s at same time. The main goal complete eradication purging latently infected cells patients’ bodies. A potential strategy called “lock-in apoptosis” targets budding phase cycle leads susceptibility apoptosis elimination reservoirs and, ultimately, eradication. work intends present advantages disadvantages United States Food Drug Administration (FDA)-approved anti-HIV-1 drugs as well plausible strategies design development more compounds with better potency, favorable pharmacokinetic profiles, improved safety issues.

Language: Английский

Citations

15
Rotten to the core: antivirals targeting the HIV-1 capsid core DOI Creative Commons
William M. McFadden, Alexa A. Snyder, Karen A. Kirby

et al.

Retrovirology, Journal Year: 2021, Volume and Issue: 18(1)

Published: Dec. 22, 2021

Abstract The capsid core of HIV-1 is a large macromolecular assembly that surrounds the viral genome and an essential component infectious virus. In addition to its multiple roles throughout life cycle, interacts with host factors. Owing indispensable nature, has been target numerous antiretrovirals, though most capsid-targeting molecules have not had clinical success until recently. Lenacapavir, long-acting drug targets capsid, currently undergoing phase 2/3 trials, making it successful inhibitor to-date. this review, we detail role protein in virus categorize antiviral compounds based on their targeting five sites within discuss molecular interactions mechanisms action. diverse range inhibition provides insight into possible new strategies for designing novel drugs furthers our understanding biology. Graphical

Language: Английский

Citations

53
Infectious RNA: Human Immunodeficiency Virus (HIV) Biology, Therapeutic Intervention, and the Quest for a Vaccine DOI Creative Commons
Yasemin van Heuvel, Stefanie Schatz, Jamila Franca Rosengarten

et al.

Toxins, Journal Year: 2022, Volume and Issue: 14(2), P. 138 - 138

Published: Feb. 14, 2022

Different mechanisms mediate the toxicity of RNA. Genomic retroviral mRNA hijacks infected host cell factors to enable virus replication. The viral genomic RNA human immunodeficiency (HIV) encompasses nine genes encoding in less than 10 kb all proteins needed for replication susceptible cells. To do so, undergoes complex alternative splicing facilitate synthesis structural, accessory, and regulatory proteins. However, HIV strongly relies on machinery recruiting cellular complete its cycle. Antiretroviral therapy (ART) targets different steps cycle, preventing disease progression acquired syndrome (AIDS). comprehension immune system interaction with has fostered development a variety vaccine platforms. Despite encouraging provisional results trials, no effective been developed, yet. novel promising platforms are currently under investigation.

Language: Английский

Citations

38
Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors DOI Creative Commons
Yuta Hikichi, Jonathan R. Grover,

Alicia Schäfer

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(9)

Published: March 1, 2024

People living with human immunodeficiency virus (HIV) receiving integrase strand transfer inhibitors (INSTIs) have been reported to experience virological failure in the absence of resistance mutations integrase. To elucidate INSTI mechanisms, we propagated HIV-1 presence escalating concentrations dolutegravir. became resistant dolutegravir by sequentially acquiring envelope glycoprotein (Env) and nucleocapsid protein. The selected Env enhance ability spread via cell-cell transfer, thereby increasing multiplicity infection (MOI). While confer broad multiple classes antiretrovirals, fold is ~2 logs higher for INSTIs than other drugs. We demonstrate that are more readily overwhelmed high MOI antiretrovirals. Our findings advance understanding how can evolve including potent INSTIs, drug-target gene mutations.

Language: Английский

Citations

7
The Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target DOI Creative Commons
Matthias Niklasch, Peter Jan Zimmermann, Michael Nassal

et al.

Biomedicines, Journal Year: 2021, Volume and Issue: 9(11), P. 1577 - 1577

Published: Oct. 29, 2021

Hepatitis B virus (HBV) is a small enveloped DNA which replicates its tiny 3.2 kb genome by reverse transcription inside an icosahedral nucleocapsid, formed single ~180 amino acid capsid, or core, protein (Cp). HBV causes chronic hepatitis (CHB), severe liver disease responsible for nearly million deaths each year. Most of HBV's only seven primary gene products are multifunctional. Though less obvious than the multi-domain polymerase, P protein, this equally crucial Cp with multiple roles in viral life-cycle. provides stable container during extracellular phases, allows directed intracellular transport and timely release from subsequent assembly new nucleocapsids around pregenomic (pg) RNA, forming distinct compartment transcription. These opposing features enabled dynamic post-transcriptional modifications result structural alterations. Their perturbation capsid modulators (CAMs) promising antiviral concept. CAMs inappropriately accelerate and/or distort shell. We summarize functional, biochemical, dynamics Cp, discuss therapeutic potential based on clinical data. Presently, appear as valuable addition but not substitute existing therapies. However, part rational combination therapies may bring ambitious goal cure CHB closer to reality.

Language: Английский

Citations

39