A Phase 2b Multicenter, Randomized, Open-Label Study Comparing the Efficacy, Safety, PK, and Tolerability of VH3810109, Administered Either Intravenously Or As A Subcutaneous Infusion With rHuPH20, in Combination With CAB LA to Standard of Care in Virologically Suppressed Adults Living With HIV

The study aims at evaluating the efficacy of VH3810109, dosed in accordance with the dosing schedule as either intravenous (IV) infusion or subcutaneous (SC) infusion with recombinant hyaluronidase (rHuPH20), in combination with cabotegravir (CAB) intramuscular (IM) dosed in accordance with the dosing schedule in virologically suppressed, Antiretroviral therapy (ART)-experienced adult participants living with HIV.

Start Date17 Aug 2023

Sponsor / Collaborator

ViiV Healthcare Ltd.

NCT05291520

/ CompletedPhase 1

A Phase 1, Open-Label, Single-Dose Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, GSK3810109, Administered Either Subcutaneously or Intravenously With Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults

An open-label, two part study to assess the safety, tolerability, and PK of VH3810109 in healthy adult participants. Participants will receive a single SC or IV dose of VH3810109 co-administered with rHuPH20 and will be followed up for 24 weeks.

Start Date23 Feb 2022

Sponsor / Collaborator

ViiV Healthcare Ltd.

100 Clinical Results associated with HIV envelope protein gp120 x CD4

100 Translational Medicine associated with HIV envelope protein gp120 x CD4

0 Patents (Medical) associated with HIV envelope protein gp120 x CD4

Literatures (Medical) associated with HIV envelope protein gp120 x CD4

20 May 2019·Medicinal ChemistryQ4 · MEDICINE

Rational Design of Colchicine Derivatives as anti-HIV Agents via QSAR and Molecular Docking

Q4 · MEDICINE

Article

Author: Prachayasittikul, Virapong ; Prachayasittikul, Supaluk ; Nantasenamat, Chanin ; Songtawee, Napat ; Worachartcheewan, Apilak ; Siriwong, Suphakit

Background:Human immunodeficiency virus (HIV) is an infective agent that causes an acquired immunodeficiency syndrome (AIDS). Therefore, the rational design of inhibitors for preventing the progression of the disease is required.Objective:This study aims to construct quantitative structure-activity relationship (QSAR) models, molecular docking and newly rational design of colchicine and derivatives with anti-HIV activity.Methods:A data set of 24 colchicine and derivatives with anti-HIV activity were employed to develop the QSAR models using machine learning methods (e.g. multiple linear regression (MLR), artificial neural network (ANN) and support vector machine (SVM)), and to study a molecular docking.Results:The significant descriptors relating to the anti-HIV activity included JGI2, Mor24u, Gm and R8p+ descriptors. The predictive performance of the models gave acceptable statistical qualities as observed by correlation coefficient (Q2) and root mean square error (RMSE) of leave-one out cross-validation (LOO-CV) and external sets. Particularly, the ANN method outperformed MLR and SVM methods that displayed LOO−CV 2 Q and RMSELOO-CV of 0.7548 and 0.5735 for LOOCV set, and Ext 2 Q of 0.8553 and RMSEExt of 0.6999 for external validation. In addition, the molecular docking of virus-entry molecule (gp120 envelope glycoprotein) revealed the key interacting residues of the protein (cellular receptor, CD4) and the site-moiety preferences of colchicine derivatives as HIV entry inhibitors for binding to HIV structure. Furthermore, newly rational design of colchicine derivatives using informative QSAR and molecular docking was proposed.Conclusion:These findings serve as a guideline for the rational drug design as well as potential development of novel anti-HIV agents.

01 Mar 2019·International Journal of Biological MacromoleculesQ1 · CHEMISTRY

Analysis of interaction between sulfated polysaccharides and HIV oligopeptides by surface plasmon resonance

Q1 · CHEMISTRY

Article

Author: Miyazaki, Kensuke ; Battulga, Tungalag ; Ishimura, Takahisa ; Yoshida, Takashi ; Kanamoto, Taisei ; Tumurbaatar, Oyunjargal ; Nakashima, Hideki ; Ganzorig, Oyundelger

This study aims to quantitatively investigate the interaction between sulfated polysaccharides with potent anti-HIV activity, dextran and curdlan sulfates with negatively charged sulfate groups, and poly-L-lysine as a model protein and oligopeptides from a HIV surface glycoprotein gp120 with positively charged amino acids using surface plasmon resonance (SPR) and dynamic light scattering (DLS) to elucidate the anti-HIV mechanism of sulfated polysaccharides. The apparent association- (k_a) and dissociation rate (k_d) constants of dextran and curdlan sulfates against poly-L-lysine were k_a = 6.92 × 10⁴-2.17 × 10⁶ 1/Ms and k_d = 4.29 × 10^-5-2.22 × 10^-4 1/s; these kinetic constants were dependent on the molecular weights and degree of sulfation of sulfated polysaccharides. For interaction, the three oligopeptides from the HIV gp120 were peptide A ²⁹⁷TRPNNNTRKRIRIQRGPGRA³¹⁶ with several lysine (K) and arginine (R) in the V3 loop region, peptide B ⁴⁹³PLGVAPTKAKRRVVQREKR⁵¹¹ with several K and R in the C-terminus region, and oligopeptide C ³⁶²KQSSGGDPEIVTHSFNCGG³⁸⁰ with few basic amino acids in the CD4 binding domain. Sulfated polysaccharides exhibited strong interaction against oligopeptides A and B, (k_a = 5.48 × 10⁴-2.96 × 10⁶ 1/Ms. and k_d = 1.74 × 10^-4-6.24 × 10^-3 1/s), no interaction was noted against oligopeptide C. Moreover, the particle size and zeta potential by DLS indicated the interaction between sulfated polysaccharides and oligopeptides A and B, suggesting the anti-HIV mechanism of sulfated polysaccharides to be the electrostatic interaction of negatively charged sulfated polysaccharides and HIV at the positively charged amino acid regions.

01 Apr 2016·Journal of VirologyQ2 · MEDICINE

Conformational Epitope-Specific Broadly Neutralizing Plasma Antibodies Obtained from an HIV-1 Clade C-Infected Elite Neutralizer Mediate Autologous Virus Escape through Mutations in the V1 Loop

Q2 · MEDICINE

Article

Author: Bhattacharya, Jayanta ; Murugavel, Kailapuri G. ; Deshpande, Suprit ; Boliar, Saikat ; Shrivastava, Tripti ; Kumar, Rajesh ; Chakrabarti, Bimal K. ; Bansal, Manish ; Koff, Wayne C. ; Patil, Shilpa ; Srikrishnan, Aylur K. ; Samal, Sweety ; Solomon, Suniti ; Goyal, Rajat ; Simek, Melissa ; Chaudhary, Nakul Kumar

ABSTRACTBroadly neutralizing antibodies isolated from infected patients who are elite neutralizers have identified targets on HIV-1 envelope (Env) glycoprotein that are vulnerable to antibody neutralization; however, it is not known whether infection established by the majority of the circulating clade C strains in Indian patients elicit neutralizing antibody responses against any of the known targets. In the present study, we examined the specificity of a broad and potent cross-neutralizing plasma obtained from an Indian elite neutralizer infected with HIV-1 clade C. This plasma neutralized 53/57 (93%) HIV pseudoviruses prepared with Env from distinct HIV clades of different geographical origins. Mapping studies using gp120 core protein, single-residue knockout mutants, and chimeric viruses revealed that G37080 broadly cross-neutralizing (BCN) plasma lacks specificities to the CD4 binding site, gp41 membrane-proximal external region, N160 and N332 glycans, and R166 and K169 in the V1-V3 region and are known predominant targets for BCN antibodies. Depletion of G37080 plasma with soluble trimeric BG505-SOSIP.664 Env (but with neither monomeric gp120 nor clade C membrane-proximal external region peptides) resulted in significant reduction of virus neutralization, suggesting that G37080 BCN antibodies mainly target epitopes on cleaved trimeric Env. Further examination of autologous circulating Envs revealed the association of mutation of residues in the V1 loop that contributed to neutralization resistance. In summary, we report the identification of plasma antibodies from a clade C-infected elite neutralizer that mediate neutralization breadth via epitopes on trimeric gp120 not yet reported and confer autologous neutralization escape via mutation of residues in the V1 loop.IMPORTANCE A preventive vaccine to protect against HIV-1 is urgently needed. HIV-1 envelope glycoproteins are targets of neutralizing antibodies and represent a key component for immunogen design. The mapping of epitopes on viral envelopes vulnerable to immune evasion will aid in defining targets of vaccine immunogens. We identified novel conformational epitopes on the viral envelope targeted by broadly cross-neutralizing antibodies elicited in natural infection in an elite neutralizer infected with HIV-1 clade C. Our data extend our knowledge on neutralizing epitopes associated with virus escape and potentially contribute to immunogen design and antibody-based prophylactic therapy.

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