In-silico drug design: An approach which revolutionarised the drug discovery process

Wadood, Abdul; Ahemad, Nafees; Shah, Lubna; Ahmad, Ateeque; Hassan, Hazem E.; Shams, Sulaiman

doi:10.13172/2054-4057-1-1-1119

Cited by 71 publications

(56 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The molecular docking approach to identify the drug targets has become one of the most popular methods for ligand-based computer-aided drug discovery (LB-CADD). In current era, with this approach, big data of drug libraries can be analyzed and annotated quickly and immense amount of energy, time, and costs related to CADD can be saved (Wadood et al, 2013;Yu & Mackerell, 2017). Currently, there are no effective treatments available to cure COVID-19 virus, and hence, identi cation of potential drug targets is urgently needed.…”

Section: Resultsmentioning

confidence: 99%

Identification of phytochemical inhibitors against main protease of COVID-19 using molecular modeling approaches

Kumar

Choudhir

Shukla

et al. 2020

Preprint

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel corona virus that causes corona virus disease 2019 (COVID-19). The COVID-19 rapidly spread across the nations with high mortality rate even as very little is known to contain the virus at present. In the current study, we report novel natural metabolites namely, ursolic acid, carvacrol and oleanolic acid as the potential inhibitors against main protease (Mpro) of COVID-19 by using integrated molecular modeling approaches. From a combination of molecular docking and molecular dynamic (MD) simulations, we found three ligands bound to protease during 50 ns of MD simulations. Furthermore, the molecular mechanic/generalized/Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations showed that these chemical molecules have stable and favourable energies causing strong binding with binding site of Mpro protein. All these three molecules, namely, ursolic acid, carvacrol and oleanolic acid, have passed the ADME (Absorption, Distribution, Metabolism, and Excretion) property as well as Lipinski’s rule of five. The study provides a basic foundation and suggests that the three phytochemicals, viz. ursolic acid, carvacrol and oleanolic acid could serve as potential inhibitors in regulating the Mpro protein's function and controlling viral replication.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of phytochemical inhibitors against main protease of COVID-19 using molecular modeling approaches

Kumar

Choudhir

Shukla

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…[24] Target identification and prediction of novel drugs In-silico methods have been of great importance (A Wadood et al,2013). [1] There is compelling evidence that small molecule inhibitors of PTP1B may be effective in treating insulin resistance at an early stage, thereby leading to a prevention strategy for T2DM and obesity (Rao et al,2006). [22] 2.…”

Section: Secondary Phosphate Sitementioning

confidence: 99%

Identification of Cost Effective Drug Through in-Silico Approach of Catharanthus Roseus Plant Ligand-Receptor Docking for Type 2 Diabetes Niddm.

Tolambiya¹

2017

WJPPS

View full text Add to dashboard Cite

Objective:-Diabetes type2 is common disease found in every agesegment of human beings. This study was proposed to design cost effective drug through herbal medicinal plant Catharanthus roseus and its parts, directly or indirectly being used for diabetes treatment.Methodology:-GCMS is conducted on alcoholic stem extraction to identify the different alkaloids substances. The chemical structure of these alkaloids was identified through pubchem database. PTB1B is a novel target for type 2 diabetes and its 3D structure designed by target sequence. The blast of target sequence was performed with PDB to get template 1NL9 which is 100% identical with target sequence. As a result, 1NL9 resolution is found at least 2.0 Angstroms and its R-factor is not greater than 20.0, hence this structure is considered as a model or a receptor. Docking of these chemical structure of alkaloids against protein-tyrosine phosphatase1B(PTP1B)is done through Auto dock 4.2 software. The present study involves computation of 21 compound to identify the least energy molecules. These molecules follows the Lipinski's rule and assist the drug development avoiding expensive post clinical experiments. This process provides the actual active compound for drug discovery. Conclusion:-It is anticipated that 3-Nitrophthalic Acid has least energy molecule and it fulfills the Lipinski rules of five, hence it could inhibit the PTP1B and improve insulin action for recovery of Type-2 Diabetes. Such studies reduce the time and costs involved in drug discovery process and have no adverse effects on the environment.

show abstract

“…The in silico methods, comprised of computational techniques, facilitate the process of drug discovery by making the analysis worthwhile, efficient and also saves resource consumption [15,16]. Drug discovery, through computational analysis, helps to identify the potent medicinal compounds having inhibitory potential and high efficiency [17]. The main purpose of this study was to discover some novel and potent inhibitors having good pharmacological profiles and reactivity.…”

Section: Introductionmentioning

confidence: 99%

in silico discovery of potential inhibitors against Dipeptidyl Peptidase-4: A major biological target of Type-2 diabetes mellitus

Subhani¹,

Arif²,

Hussain³

et al. 2020

Int J Clin Microbiol Biochem Technol

View full text Add to dashboard Cite

Objectives: Type-2 diabetes mellitus, caused by impaired secretion of insulin, is becoming one of the health hazardous threats to human lives across the world. Its prevalence is rising with time. In this study, 2750 phytochemicals, that are considered to have great ability to eliminate diseases caused by different viruses and bacteria, are obtained from different medicinal plants and discovery of inhibitors through in silico method was performed against Dipeptidyl peptidase-4 (DPP4). Method: The pharmacological assessment and pharmacokinetics of phytochemicals, molecular docking and density functional theory (DFT) analysis helped to explore the inhibitory action of phytochemicals against DPP4. Total forty-nine phytochemicals were screened initially to reduce the number of compounds to be analyzed further based on a threshold of binding affinity ≥-5.5 kcal/mol and were considered for further computational studies to analyze their inhibitory effects for DPP4. For comparison and validation of the results of present study, various previously reported and experimentally validated compounds were docked with the DPP4. For these dockings, binding affinity was predicted and compared with those of phytochemicals to check if these phytochemicals are competent enough to be used as an inhibitor in the treatment of diabetes mellitus in the future. Results: Only four phytochemicals showed binding affinity greater than those of experimentally validated compounds. These included two phytochemicals from Silybum marianum, i.e. Diprenyleriodictyol and Taxifolin and while other two phytochemicals from Santolina insularis and Erythrina Varigatae i.e. Papraline and Osajin respectively. The reactivity levels for these four phytochemicals with the binding site residues of DPP4 were obtained by DFT based analysis, in which ELUMO, EHOMO and band energy gap were computed. Conclusion: Based on these results, it is concluded that these four phytochemicals, after passing through in vitro and in vivo validation, can be utilized as potential DPP4 inhibitors as they have strong properties as compared to those of various experimentally validated inhibitors. with about 300 million cases is to be expected worldwide by 2025 [3]. Both genetic and environmental factors are involved in pathogenicity of type-2 diabetes. It may result in many other disorders like obesity, increased thirst, frequent urination and physical inactivity [4]. There are many symptoms of type-2 diabetes but one of the main symptoms is of raising the blood glucose levels, which is usually caused by impaired In silico discovery of potential inhibitors against Dipeptidyl Peptidase-4: A major biological target of Type-2 diabetes mellitus

show abstract

In-silico drug design: An approach which revolutionarised the drug discovery process

Cited by 71 publications

References 21 publications

Identification of phytochemical inhibitors against main protease of COVID-19 using molecular modeling approaches

Identification of phytochemical inhibitors against main protease of COVID-19 using molecular modeling approaches

Identification of Cost Effective Drug Through in-Silico Approach of Catharanthus Roseus Plant Ligand-Receptor Docking for Type 2 Diabetes Niddm.

in silico discovery of potential inhibitors against Dipeptidyl Peptidase-4: A major biological target of Type-2 diabetes mellitus

Contact Info

Product

Resources

About