Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

Kumar, Durgesh; Kumari, Kamlesh; Vishvakarma, Vijay Kumar; Jayaraj, Abhilash; Kumar, Dilip; R, Venkatesh Kumar; Patel, Rajan; Kumar, Vinod; Dass, Sujata K.; Chandra, Ramesh; Singh, Prashant

doi:10.1080/07391102.2020.1779131

Cited by 53 publications

(47 citation statements)

References 71 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In silico methods are being explored by the researchers due to the efficiency and strategic approach. Computational tools are used to create a library and filtering them to get the biological potent compound against a receptor [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. In this work, authors have designed a multi-component reaction (MCR) to produce pyrazolophthalazine via the one pot reaction between benzaldehyde, 2,3-dihydrophthalazine-1,4-dione and oxazolidine-2,4-dione (OZD) and its feasibility was studied through DFT method using Gaussian 09.…”

Section: Introductionmentioning

confidence: 99%

In-silico prediction of novel drug-target complex of nsp3 of CHIKV through molecular dynamic simulation

Kumar

Meena

Kumari

et al. 2020

Heliyon

Self Cite

View full text Add to dashboard Cite

Literature reported that nsp3 of CHIKV is an important target for the designing of drug as it involves in the replication, survival etc. Herein, about eighteen million molecules available in the ZINC database are filtered against nsp3 using RASPD. Top five hit drug molecules were then taken from the total screened molecules (6988) from ZINC database. Then, a one pot-three components reaction is designed to get the pyrazolophthalazine and its formation was studied using DFT method. Authors created a library of 200 compounds using the product obtained in the reaction and filtered against nsp3 of CHIKV based on docking using iGEMDOCK, a computational tool. Authors have studied the best molecules after applying the the Lipinski's rule of five and bioactive score. Further, the authors took the best compound i.e. CMPD178 and performed the MD simulations and tdMD simulations with nsp3 protease using AMBER18. MD trajectories were studied to collect the information about the nsp3 of CHIKV with and without screened compound and then, MM-GBSA calculations were performed to calculate change in binding free energies for the formation of complex. The aim of the work is to find the potential candidate as promising inhibitor against nsp3 of CHIKV.

show abstract

Section: Introductionmentioning

confidence: 99%

In-silico prediction of novel drug-target complex of nsp3 of CHIKV through molecular dynamic simulation

Kumar

Meena

Kumari

et al. 2020

Heliyon

Self Cite

View full text Add to dashboard Cite

show abstract

“…Molecular docking is an interesting approach to understand the interaction of the designed molecules with the proteases of the target. The molecular docking is based on the algorithms to study the interaction based on the binding energy (Durgesh et al, 2020;Kumar et al, 2020aKumar et al, , 2020cSingh et al, 2019;Vishvakarma, Shukla, et al, 2019;. Molecular docking between the designed molecules with the main protease of the SARS-CoV-2 and Figure 2.…”

Section: Molecular Docking Of the Designed Conjugates Of Noscapine Wimentioning

confidence: 99%

DFT and docking studies of designed conjugates of noscapines & repurposing drugs: promising inhibitors of main protease of SARS-CoV-2 and falcipan-2

Kumar

et al. 2020

Journal of Biomolecular Structure and Dynamics

Self Cite

View full text Add to dashboard Cite

First case of the present epidemic, coronavirus disease (COVID-19) is reported in the Wuhan, a city of the China and all the countries throughout the world are being affected. COVID-19 is named by World Health Organization and it stands for coronavirus disease-19. As on 27 th October, 2020, 73,776,588 people around the world are infected. It is also known as SARS-CoV-2 infection. Till date, there is no promising drug or vaccine available in market to cure from this lethal infection. As the literature reported that noscapine a promising candidate to cure from malaria as well reported to be cough suppressant and anti-cancerous. In our previous work, a derivative of noscapine has shown potential behavior against the main protease of novel coronavirus or SARS-CoV-2. Based on the previous study, hybrid molecules based on noscapine and repurposing (antiviral) drugs were designed to target the main protease of novel coronavirus and falcipan-2 using molecular docking. It is proposed that the designed hydrids or conjugates may have promising antiviral property i.e. against the main protease of novel coronavirus and falcipan-2. The designed molecules were thoroughly studied by DFT and different thermodynamic parameters were determined. Further, infrared and Raman spectra of the designed hybrid molecules were determined and studied.

show abstract

“…This binding is obtained by the electrostatic and van der Waals interaction along with the hydrogen bonding. Further, the molecular interactions of best five compounds with insulin at residues level were studied [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47].…”

Section: Molecular Dockingmentioning

confidence: 99%

A Theoretical Model to Study the Interactions of Xanthene-1,2, 3-Triazolyl-N-Riboside and Xanthene-Piperidinyl-Benzisoxazole Based Conjugates With the Insulin: Design, Docking and ADME Studies

Nand¹,

Kumari²,

Singh³

2020

Preprint

Self Cite

View full text Add to dashboard Cite

Literature reported the insulin is an important for the humans and it is secreted in the pancreas and controls, regulates the glucose level. It also controls the mechanism and growth. On decreasing the amount of insulin can caused diabetes, several cancers and other disease. Therefore, there is a need to find promising candidates can binds with insulin and stabilize them. Organic compounds containing hetero atoms have lots of biological potency in different area, therefore, researchers are designing new biological potent compounds. Further, insilico studies attracted the researchers in last one decade mainly to get the drug in less time with a clear strategy. In the present work, authors have designed two types of conjugates, xanthenes with trizole as well benzisoxazole and study their interaction with the insulin using computational methods. The library of compounds was screened through molecules docking in terms of binding energy between the designed compound and the active site of the receptor. Further, their ADME properties are investigated. CMPD19 showed best binding affinity with the insulin and may be considered as oral drug based on the bioactive scores.

show abstract

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

Cited by 53 publications

References 71 publications

In-silico prediction of novel drug-target complex of nsp3 of CHIKV through molecular dynamic simulation

In-silico prediction of novel drug-target complex of nsp3 of CHIKV through molecular dynamic simulation

DFT and docking studies of designed conjugates of noscapines & repurposing drugs: promising inhibitors of main protease of SARS-CoV-2 and falcipan-2

A Theoretical Model to Study the Interactions of Xanthene-1,2, 3-Triazolyl-N-Riboside and Xanthene-Piperidinyl-Benzisoxazole Based Conjugates With the Insulin: Design, Docking and ADME Studies

Contact Info

Product

Resources

About