Withania somnifera extracts induced attenuation of HIV-1: a mechanistic approach to restrict viral infection
Jadaun P, Harshithkumar R, Gaikwad SY, Seniya C, Borse S, Gawai AA, Chavan-Gautam P, Tillu G, Mukherjee A
Virology journal · 10 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- Indian Council of Medical Research
- Government
- Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy
- University or hospital
- Savitribai Phule Pune University
- Government
- Department of Health Research, India
- Grants
- Department of Health Research, India (WSS/2020/000023/AP_WSS)
Based on 4 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2023-08-03 · Virol J · vol. 20 · issue 1 · p. 173
- Publisher
- BioMed Central
- Cited
- 14 citations · more than 94% of similar papers · 4.4× the field average
- Impact
- Top 10% most cited in its field
- References
- 53 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Phytochemicals and Medicinal Plants · HIV Research and Treatment · Biological Research and Disease Studies
- Keywords
- Withania somnifera, Biology, Reverse transcriptase, Viral replication, Cytotoxicity, Pharmacology, Virology, Integrase, Virus, Docking (animal), In vitro, Medicinal plants, Traditional medicine, Human immunodeficiency virus (HIV), Biochemistry, Medicine, Polymerase chain reaction, Botany
- MeSH
- leukocytes, mononuclear, humans, hiv-1, withania, plants, medicinal, virus diseases, plant extracts, anti-retroviral agents, molecular docking simulation
9 authors
From IN
- Pratiksha JadaunNational AIDS Research Institute
- R HarshithkumarNational AIDS Research Institute
- Shraddha GaikwadNational AIDS Research Institute
- Chandrabhan SeniyaRajiv Gandhi Technical University; VIT Bhopal University; Barkatullah University
- Swapnil BorseSavitribai Phule Pune University
- Ashish A Gawai
Abstract
Background
Several anti-retroviral drugs are available against Human immunodeficiency virus type-1, but have multiple adverse side effects. Hence, there is an incessant compulsion for effectual anti-retroviral agents with minimal or no intricacy. Traditionally, natural products have been the most successful source for the development of new medications. Withania somnifera, also known as Ashwagandha, is the utmost treasured medicinal plant used in Ayurveda, which holds the potential to give adaptogenic, immunomodulatory, and antiviral effects. However, its effect on HIV-1 replication at the cellular level has never been explored. Herein, we focused on the anti-HIV-1 activity and the probable mechanism of action of hydroalcoholic and aqueous extracts of Withania somnifera roots and its phytomolecules.
Methods
The cytotoxicity of the extracts was determined through MTT assay, while the in vitro anti-HIV-1 activity was assessed in TZM-bl cells against the HIV-1 strains of X4 and R5 subtypes. Results were confirmed in peripheral blood mononuclear cells, using the HIV-1 p24 antigen assay. Additionally, the mechanism of action was determined through the Time of Addition assay, which was further validated through the series of enzymatic assays, i.e. HIV-1 Integrase, Reverse transcriptase, and Protease assays. To explore the role of the identified active metabolites of Withania somnifera in antiretroviral activity, molecular docking analyses were performed against these key HIV-1 replication enzymes.
Results
The hydroalcoholic and aqueous extracts of Withania somnifera roots were found to be safer at the sub-cytotoxic concentrations and exhibited their ability to inhibit replication of two primary isolates of HIV-1 through cell-associated and cell-free assays, in dose-dependent kinetics. Several active phytomolecules found in Withania somnifera successfully established hydrogens bonds in the active binding pocket site residues responsible for the catalytic activity of HIV replication and therefore, signifying their role in the attenuation of HIV-1 infection as implied through the in silico molecular docking studies.
Conclusions
Our research identified both the hydroalcoholic and aqueous extracts of Withania somnifera roots as potent inhibitors of HIV-1 infection. The in silico analyses also indicated the key components of Withania somnifera with the highest binding affinity against the HIV-1 Integrase by 12-Deoxywithastramonolide and 27-Hydroxywithanone, HIV-1 Protease by Ashwagandhanolide and Withacoagin, and HIV-1 Reverse transcriptase by Ashwagandhanolide and Withanolide B, thereby showing possible mechanisms of HIV-1 extenuation. Overall, this study classified the role of Withania somnifera extracts and their active compounds as potential agents against HIV-1 infection.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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