scholarly journals HIV-1 Reverse Transcriptase Inhibition by Major Compounds in a Kenyan Multi-Herbal Composition (CareVid™): In Vitro and In Silico Contrast

2021 ◽  
Vol 14 (10) ◽  
pp. 1009
Author(s):  
Winnie Rotich ◽  
Nicholas J. Sadgrove ◽  
Eduard Mas-Claret ◽  
Guillermo F. Padilla-González ◽  
Anastasia Guantai ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Ellagic Acid ◽  
In Silico ◽  
Chemical Constituents ◽  
Herbal Product ◽  
Docking Studies ◽  
Prunus Africana ◽  
Reverse Transcriptase Enzyme ◽  
Hiv 1

CareVid is a multi-herbal product used in southwest Kenya as an immune booster and health tonic and has been anecdotally described as improving the condition of HIV-positive patients. The product is made up of roots, barks and whole plant of 14 African medicinal plants: Acacia nilotica (L.) Willd. ex Delile (currently, Vachelia nilotica (L.) P.J.H Hurter & Mabb.), Adenia gummifera (Harv.) Harms, Anthocleista grandiflora Gilg, Asparagus africanus Lam., Bersama abyssinica Fresen., Clematis hirsuta Guill. & Perr., Croton macrostachyus Hochst. ex Delile, Clutia robusta Pax (accepted as Clutia kilimandscharica Engl.), Dovyalis abyssinica (A. Rich.) Warb, Ekebergia capensis Sparm., Periploca linearifolia Quart.-Dill. & A. Rich., Plantago palmata Hook.f., Prunus africana Hook.f. Kalkman and Rhamnus prinoides L’Her. The objective of this study was to determine the major chemical constituents of CareVid solvent extracts and screen them for in vitro and in silico activity against the HIV-1 reverse transcriptase enzyme. To achieve this, CareVid was separately extracted using CH2Cl2, MeOH, 80% EtOH in H2O, cold H2O, hot H2O and acidified H2O (pH 1.5–3.5). The extracts were analysed using HPLC–MS equipped with UV diode array detection. HIV-1 reverse transcriptase inhibition was performed in vitro and compared to in silico HIV-1 reverse transcriptase inhibition, with the latter carried out using MOE software, placing the docking on the hydrophobic pocket in the subdomain of p66, the NNRTI pocket. The MeOH and 80% EtOH extracts showed strong in vitro HIV-1 reverse transcriptase inhibition, with an EC50 of 7 μg·mL−1. The major components were identified as sucrose, citric acid, ellagic acid, catechin 3-hexoside, epicatechin 3-hexoside, procyanidin B, hesperetin O-rutinoside, pellitorine, mangiferin, isomangiferin, 4-O-coumaroulquinic acid, ellagic acid, ellagic acid O-pentoside, crotepoxide, oleuropein, magnoflorine, tremulacin and an isomer of dammarane tetrol. Ellagic acid and procyanidin B inhibited the HIV-1 reverse transcription process at 15 and 3.2 µg/mL−1, respectively. Docking studies did not agree with in vitro results because the best scoring ligand was crotepoxide (ΔG = −8.55 kcal/mol), followed by magnoflorine (ΔG = −8.39 kcal/mol). This study showed that CareVid has contrasting in vitro and in silico activity against HIV-1 reverse transcriptase. However, the strongest in vitro inhibitors were ellagic acid and procyanidin B.

SYNTHESIS AND ANTI-HIV EVALUATION OF SUBSTITUTED INDOLE-3-CARBALDEHYDE DERIVATIVES

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (02) ◽  
pp. 18-26
Author(s):  
Pankaj Wadhwa ◽  
Priti Jain ◽  
Hemant R Jadhav
Keyword(s):  
Reverse Transcriptase ◽  
In Silico ◽  
Docking Studies ◽  
Significant Inhibition ◽  
Hiv Integrase ◽  
Starting Point ◽  
Hiv Integrase Inhibitors ◽  
Anti Hiv ◽  
Hiv 1

In the present study, a series of indole-3-carbaldehydes having substituted N-sulfonyl phenyl or Nphenacyl group was synthesized and evaluated for anti-HIV activity, in particular, in vitro and in silico HIV-1 integrase inhibition. Three compounds (8b, 8c and 8g) exhibited significant inhibition of HIV-1 IN (IC50 ≤5.32 μM). Molecular docking studies were also performed to justify the IN inhibition and in vitro in silico correlation was drawn. Compound 8b exhibited significant anti-HIV activity against HIV-1 strain IIIB (IC50 3.16 μM). HIV integrase inhibitors are also reported to inhibit reverse transcriptase. When 8b was further examined against various single and double mutant reverse transcriptase (RT) strains, it showed promising activity against E138K with IC50 value of 2.43 μM with safety index of 3. Therefore, compound 8b can be a starting point for the development of dual inhibitors of HIV integrase as well as reverse transcriptase.

scholarly journals HIV-1 Protease and Reverse Transcriptase Inhibitory Activities of Curcuma aeruginosa Roxb. Rhizome Extracts and the Phytochemical Profile Analysis: In Vitro and In Silico Screening

2021 ◽  
Vol 14 (11) ◽  
pp. 1115
Author(s):  
Chanin Sillapachaiyaporn ◽  
Panthakarn Rangsinth ◽  
Sunita Nilkhet ◽  
Nuntanat Moungkote ◽  
Siriporn Chuchawankul
Keyword(s):  
Antioxidant Activity ◽  
Reverse Transcriptase ◽  
In Silico ◽  
Active Sites ◽  
Profile Analysis ◽  
Total Phenolic ◽  
Inhibitory Activities ◽  
Anti Hiv ◽  
Hiv 1

Human immunodeficiency virus type-1 (HIV-1) infection causes acquired immunodeficiency syndrome (AIDS). Currently, several anti-retroviral drugs are available, but adverse effects of these drugs have been reported. Herein, we focused on the anti-HIV-1 activity of Curcuma aeruginosa Roxb. (CA) extracted by hexane (CA-H), ethyl acetate (CA-EA), and methanol (CA-M). The in vitro HIV-1 protease (PR) and HIV-1 reverse transcriptase (RT) inhibitory activities of CA extracts were screened. CA-M potentially inhibited HIV-1 PR (82.44%) comparable to Pepstatin A (81.48%), followed by CA-EA (67.05%) and CA-H (47.6%), respectively. All extracts exhibited moderate inhibition of HIV-1 RT (64.97 to 76.93%). Besides, phytochemical constituents of CA extracts were identified by GC-MS and UPLC-HRMS. Fatty acids, amino acids, and terpenoids were the major compounds found in the extracts. Furthermore, drug-likeness parameters and the ability of CA-identified compounds on blocking of the HIV-1 PR and RT active sites were in silico investigated. Dihydroergocornine, 3β,6α,7α-trihydroxy-5β-cholan-24-oic acid, and 6β,11β,16α,17α,21-Pentahydroxypregna-1,4-diene-3,20-dione-16,17-acetonide showed strong binding affinities at the active residues of both HIV-1 PR and RT. Moreover, antioxidant activity of CA extracts was determined. CA-EA exhibited the highest antioxidant activity, which positively related to the amount of total phenolic content. This study provided beneficial data for anti-HIV-1 drug discovery from CA extracts.

scholarly journals Methoxyflavones from Marcetia taxifolia as HIV-1 Reverse Transcriptase Inhibitors

2017 ◽  
Vol 12 (11) ◽  
pp. 1934578X1701201 ◽  
Author(s):  
Joseph T Ortega ◽  
María Luisa Serrano ◽  
Alírica I Suárez ◽  
Jani Baptista ◽  
Flor H Pujol ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Reverse Transcriptase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Antitumor Agents ◽  
In Silico Prediction ◽  
Reverse Transcriptase Inhibitors ◽  
Hiv 1

Methoxyflavones are flavonoid widely distributed in plants and has been reported as potent antitumor agents and some of them have shown activity against HIV-1. In this work, two methoxyflavones isolated from Marcetia taxifolia were evaluated in vitro and in silico as HIV-1 inhibitors. Pentamethoxyflavone (5,3’-dihydroxy-3,6,7,8,4’-pentamethoxyflavone) (PMF) and Hexamethoxyflavone (5-Hydroxy-3,6,7,8,3’,4’-hexamethoxyflavone) (HMF) showed activity against HIV-1. The EC50 for HMF was 0.05 μM and 0.04 μM for PMF. The methoxyflavones also inhibited HIV-1 reverse transcriptase (RT), with an IC50 of 4.1 μM for HMF and 0.4 μM for PMF. PMF exhibited an IC50 lower than nevirapine (1.4 μM). These results are in agreement with the in silico prediction for the interaction of these flavonoids with RT. Furthermore, the effect of some methoxyflavones with different patterns of methoxylation was evaluated on RT activity in a virtual screening; found that the inhibitory activity was inversely proportional to the degree of methoxylation.

scholarly journals In Vitro HIV-1 Evolution in Response to Triple Reverse Transcriptase Inhibitors & In Silico Phenotypic Analysis

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61102 ◽  
Author(s):  
Barbara A. Rath ◽  
Kaveh Pouran Yousef ◽  
David K. Katzenstein ◽  
Robert W. Shafer ◽  
Christof Schütte ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
In Silico ◽  
Reverse Transcriptase Inhibitors ◽  
Phenotypic Analysis ◽  
Hiv 1

scholarly journals Desain dan Studi In Silico Senyawa Turunan Kuwanon-H sebagai Kandidat Obat Anti-HIV

2018 ◽  
Vol 4 (1) ◽  
pp. 57-66
Author(s):  
Ruswanto Ruswanto ◽  
Tifa Nofianti ◽  
Richa Mardianingrum ◽  
Tresna Lestari
Keyword(s):  
Decision Tree ◽  
Reverse Transcriptase ◽  
In Silico ◽  
Morus Alba ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five ◽  
Anti Hiv ◽  
Hiv 1

Kuwanon-H merupakan senyawa flavonoid dari kulit akar  murbei (Morus alba L) yang secara in vitro berpotensi sebagai anti-HIV dibanding senyawa flavonoid lainnya yang terkandung dalam kulit akar murbei seperti morusin dan morusin 4′-glucosida. Telah dilakukan penelitian desain senyawa, penambatan molekular menggunakan ArgusLab 4.0.1 dengan metode ArgusDock, penerapan aturan Lipinski’s Rule of Five menggunakan Marvin Sketch 5.2.5.1dan uji toksisitas menggunakan aplikasi Toxtree secara in silico terhadap turunan senyawa kuwanon-H. Desain enam puluh senyawa turunan kuwanon-H dilakukan dengan cara model pendekatan Topliss pada rantai samping alifatiknya. Hasil penambatan ke-60 turunan senyawa pada reseptor HIV-1 Reverse Transcriptase (1REV) menunjukkan bahwa senyawa terbaik yaitu 3-[(2Z)-3-(siklopropilmetil)but-2-en-1-il]-8-[6-({3-[(2Z)-3-(siklopropilmetil)but-2-en-1-il]-2,4-dihidroksifenil}karbonil)-5-(2,4-di-hidroksilfenil)-3-metilsiklohek-2-en-1-il]-2-(2,4-dihidroksilfenil),7-dihidroksi-4H-kromen-4-on dengan nilai energi bebas yang lebih rendah (-12.5798 kkal/mol) dibandingkan ligan asli (-11.0445 kkal/mol) dan kuwanon-H (-11.0189 kkal/mol). Senyawa terbaik ini tidak memenuhi aturan Lipinski’s Rule of Five. Hasil prediksi uji toksisitas senyawa terbaik menurut parameter Cramer Rules termasuk kategori III, yaitu diprediksi memiliki toksisitas tinggi, menurut parameter Benigni/Bossa Rulebase diprediksi senyawa yang diuji tidak bersifat karsinogenik, genotoksik, dan nongenotoksik, sedangkan menurut parameter Kroes TTC decision tree diprediksi senyawa uji berpotensi toksik.DOI:http://dx.doi.org/10.15408/jkv.v4i1.6867 

scholarly journals In Vitro Anti-HIV-1 Reverse Transcriptase and Integrase Properties of Punica granatum L. Leaves, Bark, and Peel Extracts and Their Main Compounds

Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2124
Author(s):  
Cinzia Sanna ◽  
Arianna Marengo ◽  
Stefano Acquadro ◽  
Alessia Caredda ◽  
Roberta Lai ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Ellagic Acid ◽  
Punica Granatum ◽  
Rnase H ◽  
Hydrolyzable Tannins ◽  
Ic50 Values ◽  
Anti Hiv ◽  
Punica Granatum L ◽  
Hiv 1

In a search for natural compounds with anti-HIV-1 activity, we studied the effect of the ethanolic extract obtained from leaves, bark, and peels of Punica granatum L. for the inhibition of the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) and integrase (IN) LEDGF-dependent activities. The chemical analyses led to the detection of compounds belonging mainly to the phenolic and flavonoid chemical classes. Ellagic acid, flavones, and triterpenoid molecules were identified in leaves. The bark and peels were characterized by the presence of hydrolyzable tannins, such as punicalins and punicalagins, together with ellagic acid. Among the isolated compounds, the hydrolyzable tannins and ellagic acid showed a very high inhibition (IC50 values ranging from 0.12 to 1.4 µM and 0.065 to 0.09 µM of the RNase H and IN activities, respectively). Of the flavonoids, luteolin and apigenin were found to be able to inhibit RNase H and IN functions (IC50 values in the 3.7–22 μM range), whereas luteolin 7-O-glucoside showed selective activity for HIV-1 IN. In contrast, betulinic acid, ursolic acid, and oleanolic acid were selective for the HIV-1 RNase H activity. Our results strongly support the potential of non-edible P. granatum organs as a valuable source of anti-HIV-1 compounds.

Evaluation of Phytopolyphenols for their gp120-CD4 Binding Inhibitory Properties by In Silico Molecular Modelling & In Vitro Cell Line Studies

2019 ◽  
Vol 17 (2) ◽  
pp. 102-113 ◽  
Author(s):  
Amit Mirani ◽  
Harish Kundaikar ◽  
Shilpa Velhal ◽  
Vainav Patel ◽  
Atmaram Bandivdekar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Gallic Acid ◽  
Cell Line ◽  
Ellagic Acid ◽  
Inhibitory Activity ◽  
In Silico ◽  
Early Stage ◽  
Binding Mode ◽  
Hiv 1

Background:Lack of effective early-stage HIV-1 inhibitor instigated the need for screening of novel gp120-CD4 binding inhibitor. Polyphenols, a secondary metabolite derived from natural sources are reported to have broad spectrum HIV-1 inhibitory activity. However, the gp120-CD4 binding inhibitory activity of polyphenols has not been analysed in silico yet.Objectives:To establish the usage of phytopolyphenols (Theaflavin, Epigallocatechin (EGCG), Ellagic acid and Gallic acid) as early stage HIV-1 inhibitor by investigating their binding mode in reported homology of gp120-CD4 receptor complex using in silico screening studies and in vitro cell line studies.Methods:The in silico molecular docking and molecular simulation studies were performed using Schrödinger 2013-2 suite installed on Fujitsu Celsius Workstation. The in vitro cell line studies were performed in the TZM-bl cell line using MTT assay and β-galactosidase assay.Results:The results of molecular docking indicated that Theaflavin and EGCG exhibited high XP dock score with binding pose exhibiting Van der Waals interaction and hydrophobic interaction at the deeper site in the Phe43 cavity with Asp368 and Trp427. Both Theaflavin and EGCG form a stable complex with the prepared HIV-1 receptor and their binding mode interaction is within the vicinity 4 Å. Further, in vitro cell line studies also confirmed that Theaflavin (SI = 252) and EGCG (SI = 138) exert better HIV-1 inhibitory activity as compared to Ellagic acid (SI = 30) and Gallic acid (SI = 34).Conclusions:The results elucidate a possible binding mode of phytopolyphenols, which pinpoints their plausible mechanism and directs their usage as early stage HIV-1 inhibitor.

Design, synthesis, in vitro and in silico studies of novel 4-oxoquinoline ribonucleoside derivatives as HIV-1 reverse transcriptase inhibitors

2020 ◽  
Vol 194 ◽  
pp. 112255
Author(s):  
Luana da S.M. Forezi ◽  
Mariana M.J. Ribeiro ◽  
Andressa Marttorelli ◽  
Juliana L. Abrantes ◽  
Carlos R. Rodrigues ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
In Silico ◽  
Reverse Transcriptase Inhibitors ◽  
Design Synthesis ◽  
In Silico Studies ◽  
Hiv 1

scholarly journals Glycosylated Flavonoids from Psidium guineense as Major Inhibitors of HIV-1 Replication in vitro

2017 ◽  
Vol 12 (7) ◽  
pp. 1934578X1701200
Author(s):  
Joseph T Ortega ◽  
Omar Estrada ◽  
Maria L Serrano ◽  
Whendy Contreras ◽  
Giovannina Orsini ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Reverse Transcriptase ◽  
In Silico ◽  
Biological Activities ◽  
In Silico Prediction ◽  
Flavonoid Quercetin ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Hiv 1

Flavonoids are present in practically all plants and many biological activities have been described for them. The flavonoid quercetin is a common molecule for which anti-HIV activity has been demonstrated. Avicularin and guajaverin are derivatives of quercetin with a glycoside substituent in their structure. In this work, a mixture of both derivatives was purified from an extract of Psidium guinense. The mixture exhibited activity against HIV-1 in vitro, with an IC50 of approximately 8.5 μg/mL, which compares favorably with the IC50 of 53 μg/mL of quercetin. The mixture also inhibited HIV-1 reverse transcriptase (RT), with an IC50 of 7.2 μM, compared to 0.6 μM for quercetin. These results are in agreement with the in silico prediction for the interaction of these flavonoids with RT and suggest that the glycosylic moiety could favor the transport of the compound into the cell. However, the glycosidic moiety might be cleaved intracellularly, being the resultant quercetin responsible for the antiviral activity.

Sign in / Sign up

Export Citation Format

Share Document