Evaluation of potential drugs against leishmaniasis targeting catalytic subunit of <i>Leishmania donovani</i> nuclear DNA primase using ligand based virtual screening, docking and molecular dynamics approaches

Bhowmik, Deep; Jagadeesan, Rahul; Rai, Praveen; Nandi, Rajat; Kothandan, Gugan; Kumar, Diwakar

doi:10.1080/07391102.2020.1739557

Cited by 18 publications

(18 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, quercetin formed at least one H-bond with ACE-2 during the 100ns simulation run ( Figure 9 E). Thus, MD simulation of our RBD-ACE-2-flavonoids complexes leads to establishing our complexes to be basically and structurally stable and reliable ( Bhowmik et al., 2020 ).…”

Section: Resultsmentioning

confidence: 90%

“…The residues from 490-510, centered as the binding site residues for RBD protein that interact with the ACE-2 receptor protein, showed the lowest fluctuations for the complex RBD-Hesperidin followed by RBD-EGCG with fluctuations value less than 0.3 nm. Results showed that these residues and active site residues for ACE-2 are relatively rigid and stable and hence displayed outstanding stability in the dynamic environment ( Figure 9 B) ( Bhowmik et al., 2020 ; Suvannang et al., 2011 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis

Bhowmik¹,

Nandi²,

Prakash³

et al. 2021

Heliyon

Self Cite

View full text Add to dashboard Cite

The outbreak of Coronavirus Disease 2019 (COVID-19) has been declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), which is being rapidly spread by the extremely spreadable and pathogenic 2019 novel coronavirus (2019-nCoV), also known as SARS-CoV-2. Pandemic incidence of COVID-19 has created a severe threat to global public health, necessitating the development of effective drugs or inhibitors or therapeutics agents against SARS-CoV-2. Spike protein (S) of the SARS-CoV-2 plays a crucial role in entering viruses into the host cell by binding to angiotensin-converting enzyme 2 (ACE-2), and this specific interaction represents a promising drug target for the identification of potential drugs. This study aimed at the receptor-binding domain of S protein (RBD of nCoV-SP) and the ACE-2 receptor as a promising target for developing drugs against SARS-CoV-2. Over 100 different flavonoids with antioxidant, anti-inflammatory, and antiviral properties from different literatures were taken as a ligand or inhibitor for molecular docking against target protein RBD of nCoV-SP and ACE-2 using PyRX and iGEMDOCK. Top flavonoids based on docking scores were selected for the pharmacokinetic study. Selected flavonoids (hesperidin, naringin, ECGC, and quercetin) showed excellent pharmacokinetics with proper absorption, solubility, permeability, distribution, metabolism, minimal toxicity, and excellent bioavailability. Molecular dynamics simulation studies up to 100 ns exhibited strong binding affinity of selected flavonoids to RBD of nCoV-SP and ACE-2, and the protein-ligand complexes were structurally stable. These identified lead flavonoids may act as potential compounds for developing effective drugs against SARS-CoV-2 by potentially inhibiting virus entry into the host cell.

show abstract

Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis

Bhowmik¹,

Nandi²,

Prakash³

et al. 2021

Heliyon

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, we also examine the solvent-accessible surface area (SASA) of protein-ligand complexes. SASA ensures the contribution of hydrophobic interactions of the nonpolar amino to the conformation stability of proteins in the solvent environment (Zhang et al, 2020;Bhowmik et al, 2020;Rocco et al, 2008;Kumar et al, 2018). Results show quite a stable SASA plot of E protein complex with rutin and doxycycline, which is stabilized throughout simulation with 42 nm 2 (Fig.…”

Section: Molecular Dynamic (Md) Simulation Studiesmentioning

confidence: 87%

Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches

Bhowmik

Nandi

Jagadeesan

et al. 2020

Infection, Genetics and Evolution

Self Cite

106

View full text Add to dashboard Cite

WHO has declared the outbreak of COVID-19 as a public health emergency of international concern. The evergrowing new cases have called for an urgent emergency for specific anti-COVID-19 drugs. Three structural proteins (Membrane, Envelope and Nucleocapsid protein) play an essential role in the assembly and formation of the infectious virion particles. Thus, the present study was designed to identify potential drug candidates from the unique collection of 548 anti-viral compounds (natural and synthetic anti-viral), which target SARS-CoV-2 structural proteins. High-end molecular docking analysis was performed to characterize the binding affinity of the selected drugs-the ligand, with the SARS-CoV-2 structural proteins, while high-level Simulation studies analyzed the stability of drug-protein interactions. The present study identified rutin, a bioflavonoid and the antibiotic, doxycycline, as the most potent inhibitor of SARS-CoV-2 envelope protein. Caffeic acid and ferulic acid were found to inhibit SARS-CoV-2 membrane protein while the anti-viral agent's simeprevir and grazoprevir showed a high binding affinity for nucleocapsid protein. All these compounds not only showed excellent pharmacokinetic properties, absorption, metabolism, minimal toxicity and bioavailability but were also remain stabilized at the active site of proteins during the MD simulation. Thus, the identified lead compounds may act as potential molecules for the development of effective drugs against SARS-CoV-2 by inhibiting the envelope formation, virion assembly and viral pathogenesis.

show abstract

“… Bhowmik et al, 2020 , Dallakyan and Olson, 2015 , deLeuw and Stephan, 2017 , Hebert, 2013 , Hess et al, 1997 , Johnson and Vinetz, 2020 , Liu and Wang, 2020 , Nishimura and Yamaya, 2015 , Asakura and Ogawa, 2020 , Patick and Potts, 1998 , Shi and Song, 2006 , Ungell, 1997 , Weglarz-Tomczak et al, 2020 , Wu et al, 2020 …”

Section: Uncited Referencesmentioning

confidence: 99%

“Identification of Nafamostat and VR23 as COVID-19 drug candidates by targeting 3CLpro and PLpro"

Bhowmik

Sharma

Prakash

et al. 2021

Journal of Molecular Structure

Self Cite

View full text Add to dashboard Cite

The sudden increase in the COVID-19 epidemic affected by novel coronavirus 2019 has jeopardized public health worldwide. Hence the necessities of a drug or therapeutic agent that heal SARS-CoV-2 infections are essential requirements. The viral genome encodes a large Polyprotein, further processed by the main protease/ 3C-like protease (3CL pro ) and papain-like proteases (PL pro ) into 16 nonstructural proteins to form a viral replication complex. These essential functions of 3CL pro and PL pro in virus duplication make these proteases a promising target for discovering potential therapeutic candidates and possible treatment for SARS-CoV-2 infection. This study aimed to screen a unique set of protease inhibitors library against 3CL pro and PL pro of the SARS-CoV-2. A molecular docking study was performed using PyRx to reveal the binding affinity of the selected ligands and molecular dynamic simulations were executed to assess the three-dimensional stability of protein-ligand complexes. The pharmacodynamics parameters of the inhibitors were predicted using admetSAR. The top two ligands (Nafamostat and VR23) based on docking scores were selected for further studies. Selected ligands showed excellent pharmacokinetic properties with proper absorption, bioavailability and minimal toxicity. Due to the emerging and efficiency of remdesivir and dexamethasone in healing COVID-19 patients, ADMET properties of the selected ligands were thus compared with it. MD Simulation studies up to 100ns revealed the ligands' stability at the target proteins' binding site residues. Therefore, Nafamostat and VR23 may provide potential treatment options against SARS-CoV-2 infections by potentially inhibiting virus duplication though more research is warranted.

show abstract

Evaluation of potential drugs against leishmaniasis targeting catalytic subunit of Leishmania donovani nuclear DNA primase using ligand based virtual screening, docking and molecular dynamics approaches

Cited by 18 publications

References 89 publications

Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis

Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis

Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches

“Identification of Nafamostat and VR23 as COVID-19 drug candidates by targeting 3CLpro and PLpro"

Contact Info

Product

Resources

About