scholarly journals Therapeutic potential of HIV-1 entry inhibitor peptidomimetics

2021 ◽  
pp. 153537022199087
Author(s):  
Nneka PU Korie ◽  
Kwesi Z Tandoh ◽  
Samuel K Kwofie ◽  
Osbourne Quaye
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Neutralizing Antibodies ◽  
Therapeutic Potential ◽  
Economic Cost ◽  
High Specificity ◽  
Health Concern ◽  
Future Research ◽  
Entry Inhibitors ◽  
Cost Of Production ◽  
Hiv 1

Human immunodeficiency virus 1 (HIV-1) infection remains a public health concern globally. Although great strides in the management of HIV-1 have been achieved, current highly active antiretroviral therapy is limited by multidrug resistance, prolonged use-related effects, and inability to purge the HIV-1 latent pool. Even though novel therapeutic options with HIV-1 broadly neutralizing antibodies (bNAbs) are being explored, the scalability of bNAbs is limited by economic cost of production and obligatory requirement for parenteral administration. However, these limitations can be addressed by antibody mimetics/peptidomimetics of HIV-1 bNAbs. In this review we discuss the limitations of HIV-1 bNAbs as HIV-1 entry inhibitors and explore the potential therapeutic use of antibody mimetics/peptidomimetics of HIV-1 entry inhibitors as an alternative for HIV-1 bNAbs. We highlight the reduced cost of production, high specificity, and oral bioavailability of peptidomimetics compared to bNAbs to demonstrate their suitability as candidates for novel HIV-1 therapy and conclude with some perspectives on future research toward HIV-1 novel drug discovery.

scholarly journals Human TRIM5α: Autophagy Connects Cell-Intrinsic HIV-1 Restriction and Innate Immune Sensor Functioning

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 320 ◽  
Author(s):  
Alexandra P. M. Cloherty ◽  
Anusca G. Rader ◽  
Brandon Compeer ◽  
Carla M. S. Ribeiro
Keyword(s):  
Therapeutic Potential ◽  
Innate Immune ◽  
Health Concern ◽  
Restriction Factor ◽  
Viral Reservoirs ◽  
Minimal Restriction ◽  
Immunodeficiency Virus ◽  
A Cell ◽  
Species Specific ◽  
Hiv 1

Human immunodeficiency virus-1 (HIV-1) persists as a global health concern, with an incidence rate of approximately 2 million, and estimated global prevalence of over 35 million. Combination antiretroviral treatment is highly effective, but HIV-1 patients that have been treated still suffer from chronic inflammation and residual viral replication. It is therefore paramount to identify therapeutically efficacious strategies to eradicate viral reservoirs and ultimately develop a cure for HIV-1. It has been long accepted that the restriction factor tripartite motif protein 5 isoform alpha (TRIM5α) restricts HIV-1 infection in a species-specific manner, with rhesus macaque TRIM5α strongly restricting HIV-1, and human TRIM5α having a minimal restriction capacity. However, several recent studies underscore human TRIM5α as a cell-dependent HIV-1 restriction factor. Here, we present an overview of the latest research on human TRIM5α and propose a novel conceptualization of TRIM5α as a restriction factor with a varied portfolio of antiviral functions, including mediating HIV-1 degradation through autophagy- and proteasome-mediated mechanisms, and acting as a viral sensor and effector of antiviral signaling. We have also expanded on the protective antiviral roles of autophagy and outline the therapeutic potential of autophagy modulation to intervene in chronic HIV-1 infection.

scholarly journals Influenza A Virus Antibodies with Antibody-Dependent Cellular Cytotoxicity Function

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 276 ◽  
Author(s):  
Rongyuan Gao ◽  
Zizhang Sheng ◽  
Chithra C. Sreenivasan ◽  
Dan Wang ◽  
Feng Li
Keyword(s):  
Neutralizing Antibodies ◽  
Influenza A ◽  
Therapeutic Potential ◽  
Influenza Infection ◽  
Neutralizing Antibody ◽  
Health Concern ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Effector Functions ◽  
Recent Advances

Influenza causes millions of cases of hospitalizations annually and remains a public health concern on a global scale. Vaccines are developed and have proven to be the most effective countermeasures against influenza infection. Their efficacy has been largely evaluated by hemagglutinin inhibition (HI) titers exhibited by vaccine-induced neutralizing antibodies, which correlate fairly well with vaccine-conferred protection. Contrarily, non-neutralizing antibodies and their therapeutic potential are less well defined, yet, recent advances in anti-influenza antibody research indicate that non-neutralizing Fc-effector activities, especially antibody-dependent cellular cytotoxicity (ADCC), also serve as a critical mechanism in antibody-mediated anti-influenza host response. Monoclonal antibodies (mAbs) with Fc-effector activities have the potential for prophylactic and therapeutic treatment of influenza infection. Inducing mAbs mediated Fc-effector functions could be a complementary or alternative approach to the existing neutralizing antibody-based prevention and therapy. This review mainly discusses recent advances in Fc-effector functions, especially ADCC and their potential role in influenza countermeasures. Considering the complexity of anti-influenza approaches, future vaccines may need a cocktail of immunogens in order to elicit antibodies with broad-spectrum protection via multiple protective mechanisms.

scholarly journals Antibody Conjugates for Targeted Therapy Against HIV-1 as an Emerging Tool for HIV-1 Cure

2021 ◽  
Vol 12 ◽  
Author(s):  
Jeffrey C. Umotoy ◽  
Steven W. de Taeye
Keyword(s):  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Therapeutic Index ◽  
Production Costs ◽  
People Living With Hiv ◽  
Antibody Conjugates ◽  
Number Of Treatment ◽  
Antibody Derivatives ◽  
Hiv 1

Although advances in antiretroviral therapy (ART) have significantly improved the life expectancy of people living with HIV-1 (PLWH) by suppressing HIV-1 replication, a cure for HIV/AIDS remains elusive. Recent findings of the emergence of drug resistance against various ART have resulted in an increased number of treatment failures, thus the development of novel strategies for HIV-1 cure is of immediate need. Antibody-based therapy is a well-established tool in the treatment of various diseases and the engineering of new antibody derivatives is expanding the realms of its application. An antibody-based carrier of anti-HIV-1 molecules, or antibody conjugates (ACs), could address the limitations of current HIV-1 ART by decreasing possible off-target effects, reduce toxicity, increasing the therapeutic index, and lowering production costs. Broadly neutralizing antibodies (bNAbs) with exceptional breadth and potency against HIV-1 are currently being explored to prevent or treat HIV-1 infection in the clinic. Moreover, bNAbs can be engineered to deliver cytotoxic or immune regulating molecules as ACs, further increasing its therapeutic potential for HIV-1 cure. ACs are currently an important component of anticancer treatment with several FDA-approved constructs, however, to date, no ACs are approved to treat viral infections. This review aims to outline the development of AC for HIV-1 cure, examine the variety of carriers and payloads used, and discuss the potential of ACs in the current HIV-1 cure landscape.

scholarly journals Piperazine-based HIV-1 entry inhibitors: Massive in silico library design and screening for gp120 attachment inhibitors

2018 ◽  
Author(s):  
Durbis J. Castillo-Pazos ◽  
Antonio Romo-Mancillas ◽  
Joaquín Barroso-Flores
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Chemical Space ◽  
Library Design ◽  
Promising Candidate ◽  
Entry Inhibitors ◽  
Highly Active ◽  
Gp120 Envelope ◽  
Docking Calculations ◽  
Dynamics Simulations ◽  
Hiv 1

ABSTRACTHIV-1 attachment, despite being an ideal target stage to stop infection from the beginning, remains as one of the HIV lifecycle phases with less amount of designed and commercially available inhibitors. To contribute to the urgently needed discovery of new active compounds that could become part of the current highly active antiretroviral therapy, and as an attempt to explore a massive chemical space, high-throughput virtual screening of 16.3 million combinatorially generated and piperazine-cored compounds, was accomplished. Docking calculations, molecular dynamics simulations, and QSAR analyses were carried out to assess the suitability of each ligand to bind gp120 envelope glycoprotein, thus preventing it from binding to CD4 co-receptor. Ligand 255 stands out as a promising candidate to be tested beyond computational methodologies, and the 4,5,6,7-tetrahydroindole fragment is reported as a better group to bind inside the Phe43 cavity than the substituted indoles reported in the literature.

scholarly journals Neutralizing Antibodies Do Not Mediate Suppression of Human Immunodeficiency Virus Type 1 in Elite Suppressors or Selection of Plasma Virus Variants in Patients on Highly Active Antiretroviral Therapy

2006 ◽  
Vol 80 (10) ◽  
pp. 4758-4770 ◽  
Author(s):  
Justin R. Bailey ◽  
Kara G. Lassen ◽  
Hung-Chih Yang ◽  
Thomas C. Quinn ◽  
Stuart C. Ray ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Neutralizing Antibodies ◽  
Progressive Disease ◽  
Plasma Virus ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Elite Suppressors ◽  
Hiv 1

ABSTRACT Neutralizing antibodies (NAb) against autologous virus can reach high titers in human immunodeficiency virus type 1 (HIV-1)-infected patients with progressive disease. Less is known about the role of NAb in HIV-1-infected patients with viral loads of <50 copies/ml of plasma, including patients on effective highly active antiretroviral therapy (HAART) and elite suppressors, who control HIV-1 replication without antiretroviral therapy. In this study, we analyzed full-length env sequences from plasma viruses and proviruses in resting CD4+ T cells of HAART-treated patients, elite suppressors, and untreated HIV-1-infected patients with progressive disease. For each patient group, we assessed plasma virus neutralization by autologous, contemporaneous plasma. The degree of env diversity, the number of N-linked glycosylation sites, and the lengths of variable loops were all lower in elite suppressors than in HAART-treated and untreated viremic patients. Both elite suppressors and HAART-treated patients had lower titers of NAb against HIV-1 lab strains than those of untreated viremic patients. Surprisingly, titers of NAb against autologous, contemporaneous plasma viruses were similarly low in chronic progressors, elite suppressors, and HAART-treated patients. In elite suppressors and HAART-treated patients, titers of NAb against autologous plasma viruses also did not differ significantly from titers against autologous proviruses from resting CD4+ T cells. These results suggest that high-titer NAb are not required for maintenance of viral suppression in elite suppressors and that NAb do not select plasma virus variants in most HAART-treated patients. Both drug-mediated and natural suppression of HIV-1 replication to levels below 50 copies/ml may limit the stimulation and maintenance of effective NAb responses.

scholarly journals Env-glycoprotein heterogeneity as a source of apparent synergy and enhanced cooperativity in inhibition of HIV-1 infection by neutralizing antibodies and entry inhibitors

Virology ◽  
2012 ◽  
Vol 422 (1) ◽  
pp. 22-36 ◽  
Author(s):  
Thomas J. Ketas ◽  
Sophie Holuigue ◽  
Katie Matthews ◽  
John P. Moore ◽  
Per Johan Klasse
Keyword(s):  
Neutralizing Antibodies ◽  
Entry Inhibitors ◽  
Hiv 1 ◽  
Env Glycoprotein

Differences in Suicidal Thoughts and Behaviors Among Three Racial Groups

Crisis ◽  
2020 ◽  
Vol 41 (3) ◽  
pp. 172-178
Author(s):  
Brooke A. Ammerman ◽  
Martha K. Fahlgren ◽  
Kristen M. Sorgi ◽  
Michael S. McCloskey
Keyword(s):  
Suicide Attempts ◽  
Health Concern ◽  
Future Research ◽  
Racial Groups ◽  
Contributing Factors ◽  
Suicidal Thoughts ◽  
Final Sample ◽  
And Behaviors ◽  
Assessment Procedures ◽  
Suicidal Thoughts And Behaviors

Abstract. Background: Despite being a major public health concern, it is unclear how suicidal thoughts and behaviors differentially impact separate racial groups. Aims: The aim of the current study was to examine the occurrence of nonlethal suicide events, in addition to suicide attempt characteristics and factors contributing to suicide attempts. Method: A final sample of 7,094 undergraduates from a large northeastern university, identifying as members of three racial groups (White [67.30%], Black [17.30%], and Asian [15.40%]), completed online questionnaires. Results: White participants reported increased likelihood of endorsing lifetime suicidal ideation and plan, whereas Black participants reported decreased likelihood of these events; no differences were found in rates of lifetime suicide attempts. Black participants' suicidal behavior may involve greater ambivalence of intent. A higher proportion of Asian participants endorsed interpersonal factors as contributing to their suicide attempts, whereas a greater percentage of White participants reported internal contributing factors. Limitations: Findings are limited by the sample size and assessment of lifetime suicidal thoughts and behaviors. Conclusion: The findings present a more nuanced look at attitudes and actions related to suicidal thoughts and behaviors that may inform future research and risk assessment procedures.

Broadly Neutralizing Antibodies (BNAbs): templates for HIV-1 vaccine design

2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Lixin Yan ◽  
◽  
Lihong Liu ◽  
Yilin Wang ◽  
Xi Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Design ◽  
Broadly Neutralizing Antibodies ◽  
Hiv 1
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