In-silico screening of active molecules from medicinal plant resources for controlling SARS-CoV-2 infection

The entire human population is under treat of SARS-Cov-2 virus causing life threatening complicacies. Three proteins namely papain-like protease (PLpro), 3C-like protease (3CLpro) and spike protein isolated from the virus have been targeted for formulating the antiviral medicament. Ayurvedic medicinal plants with established antiviral efficacy are great choice to design immediate treatment strategies in this trying time. Here, 9 active molecules from ayurvedic medicinal plant resources were selected, out of which only 6 have screened through ADME analysis and molecular docking was performed with the three viral proteins to understand their antiviral performances in in silico model. Outcome of this study will surely open up a floodgate of thousand new possibilities in exploiting the existing natural herbs in COVID 19 treatments.

Download Full-text

Norditerpenoids with Selective Anti-Cholinesterase Activity from the Roots of Perovskia atriplicifolia Benth.

International Journal of Molecular Sciences ◽

10.3390/ijms21124475 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4475 ◽

Cited By ~ 3

Author(s):

Sylwester Ślusarczyk ◽

F. Sezer Senol Deniz ◽

Renata Abel ◽

Łukasz Pecio ◽

Horacio Pérez-Sánchez ◽

...

Keyword(s):

Molecular Docking ◽

Medicinal Plant ◽

Neurodegenerative Diseases ◽

In Silico ◽

Cholinesterase Activity ◽

Treatment Strategies ◽

Lead Compounds ◽

Central Asian ◽

Neurodegenerative Dementias ◽

Anticholinesterase Properties

Inhibition of cholinesterases remains one of a few available treatment strategies for neurodegenerative dementias such as Alzheimer’s disease and related conditions. The current study was inspired by previous data on anticholinesterase properties of diterpenoids from Perovskia atriplicifolia and other Lamiaceae species. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition by the three new natural compounds—(1R,15R)-1-acetoxycryptotanshinone (1), (1R)-1-acetoxytanshinone IIA (2), and (15R)-1-oxoaegyptinone A (3)—as well as, new for this genus, isograndifoliol (4) were assessed. Three of these compounds exhibited profound inhibition of butyrylcholinesterase (BChE) and much weaker inhibition of acetylcholinesterase (AChE). All compounds (1–4) selectively inhibited BChE (IC50 = 2.4, 7.9, 50.8, and 0.9 µM, respectively), whereas only compounds 3 and 4 moderately inhibited AChE (IC50 329.8 µM and 342.9 µM). Molecular docking and in silico toxicology prediction studies were also performed on the active compounds. Natural oxygenated norditerpenoids from the traditional Central Asian medicinal plant P. atriplicifolia are selective BChE inhibitors. Their high potential makes them useful candidate molecules for further investigation as lead compounds in the development of a natural drug against dementia caused by neurodegenerative diseases.

Download Full-text

Gold-Aptamer-Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

10.26434/chemrxiv.8312324.v1 ◽

2019 ◽

Author(s):

Veeren Chauhan ◽

Mohamed M Elsutohy ◽

C Patrick McClure ◽

Will Irving ◽

Neil Roddis ◽

...

Keyword(s):

Nucleic Acid ◽

In Silico ◽

Point Of Care ◽

Lateral Flow ◽

Nucleic Acid Sequence ◽

In Silico Screening ◽

Lateral Flow Assays ◽

Life Threatening ◽

Software And Hardware ◽

Nucleic Acid Sequences

Enteroviruses are a ubiquitous mammalian pathogen that can produce mild to life-threatening disease. Bearing this in mind, we have developed a rapid, accurate and economical point-of-care biosensor that can detect a nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and aptamers to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral RNA sequence (23 bases), which was identified through in silico screening. Aptamers were designed to demonstrate specific complementarity towards the target enteroviral RNA to produce aggregated gold-aptamer nanoconstructs. Conserved target enteroviral nucleic acid sequence (≥ 1x10-7 M, ≥1.4×10-14 g/mL), initiates gold-aptamer-nanoconstructs disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow-assays that utilise gold-aptamer-nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (< 60 s) and could be interpreted with a bespoke software and hardware electronic interface. We anticipate our methodology will translate in-silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave-the-way forward in the clinical evaluation of disease and complement existing strategies at overcoming antimicrobial resistance.

Download Full-text