HIV-1 protease and reverse transcriptase inhibition by tiger milk mushroom (Lignosus rhinocerus) sclerotium extracts: In vitro and in silico studies

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.

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

INDIAN DRUGS ◽

10.53879/id.57.02.11912 ◽

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.

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Characterization of HIV-1 Enzyme Reverse Transcriptase Inhibition by the Compound 6-Chloro-1,4-Dihydro-4-Oxo-1-(β-D-Ribofuranosyl) Quinoline-3-Carboxylic Acid Through Kinetic and In Silico Studies

Current HIV Research ◽

10.2174/157016209788347958 ◽

2009 ◽

Vol 7 (3) ◽

pp. 327-335 ◽

Cited By ~ 9

Author(s):

Thiago Moreno Souza ◽

Diego Rodrigues ◽

Vitor Ferreira ◽

Isakelly Marques ◽

Fernanda Santos ◽

...

Keyword(s):

Carboxylic Acid ◽

Reverse Transcriptase ◽

In Silico ◽

In Silico Studies ◽

Hiv 1

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Endophytic Fungi Penicillium species BCt Phytochemicals Inhibit Replication of Enzymes of Human Immuno-deficiency Virus 1 in in vitro and in silico Studies

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2021.14.5.6 ◽

2021 ◽

Vol 14 (5) ◽

pp. 5624-5633

Author(s):

Govindappa M ◽

Channabasava ◽

Ritu Pawar ◽

Chandrasekhar Srinivasa ◽

Chandan Shivamallu ◽

...

Keyword(s):

Amino Acids ◽

Endophytic Fungi ◽

In Silico ◽

Methanol Extract ◽

Penicillium Species ◽

Ms Analysis ◽

In Silico Studies ◽

Hiv 1

The present investigation was aimed to know the coumarins in the methanol extract of endophytic fungi, Penicillium species BCt isolated from Calophyllum tomentosum bark tissues using qualitative and GC-MS analysis. The endophytic extract was evaluated for anti-HIV activity on three replicating enzymes in vitro and in silico. The methanol extract of Penicillium species confirmed the presence of coumarins in four qualitative methods and yielded four different types of coumarins in GC-MS. In GC-MS analysis, totally seven different phytochemicals were identified based on retention time and compared with available library data. The four coumarins are coumarin (2H-1-benzopyran-2-one), coumaric acid (3-benzofuran-carboxylic acid), hynecromone (coumarin 4), 4-hydroxy-9-(3-methyl-2-butyl) furo (3,2-g) chloronen-7-one) and other three are common phytochemicals. The HIV-1 RT (98) was strongly inhibited by the endophytic fungal extract compared to integrase (118) and protease (158) in vitro analysis. Highest inhibition of integrase was observed with coumarilic acid (-17.62) when attached to Glu-35, Asn-38, Ser-39 amino acids. The protease was inhibited strongly by hymecromone (-16.39) when attached to amino acids of Val-77, Glu-34, Pro-79, Gly-78. The inhibition of RT was observed with coumarilic acid by attaching to Ala-445, Arg-567, Asp-456, Glu-478, Ser-499, Asn-474 (-23.54) significantly. Based on above results, the endophytic fungal coumarins have the ability to inhibit the three replicating enzymes of HIV-1 significantly. The in-silico results are evidence for how coumarins inhibiting the HIV replicating proteins by binding at specific amino acids. The results will help to understand how and where phytochemicals bind to target proteins to inhibit their action and it may help to identification of drugs to treat HIV. To validate our results, the in vivo research is needed.

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Methoxyflavones from Marcetia taxifolia as HIV-1 Reverse Transcriptase Inhibitors

Natural Product Communications ◽

10.1177/1934578x1701201104 ◽

2017 ◽

Vol 12 (11) ◽

pp. 1934578X1701201 ◽

Cited By ~ 1

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.

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

PLoS ONE ◽

10.1371/journal.pone.0061102 ◽

2013 ◽

Vol 8 (4) ◽

pp. e61102 ◽

Cited By ~ 6

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

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

Jurnal Kimia VALENSI ◽

10.15408/jkv.v4i1.6867 ◽

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

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

Pharmaceuticals ◽

10.3390/ph14101009 ◽

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.

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