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Integrated bioinfor...
Integrated bioinformatics-cheminformatics approach toward locating pseudo-potential antiviral marine alkaloids against SARS-CoV-2-Mpro
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- Swain, Shasank S. (författare)
- ICMR Reg Med Res Ctr, Div Microbiol, Bhubaneswar 751023, Odisha, India.;ICMR Reg Med Res Ctr, NCDs, Bhubaneswar 751023, Odisha, India
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- Singh, Satya R. (författare)
- Pondicherry Univ, Dept Bioinformat, Pondicherry, India
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- Sahoo, Alaka (författare)
- Siksha O Anusandhan Deemed Univ, Dept Skin & VD, Inst Med Sci, Bhubaneswar, Odisha, India.;Siksha O Anusandhan Deemed Univ, SUM Hosp, Bhubaneswar, Odisha, India
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- Panda, Pritam Kumar, PhD Student, 1991- (författare)
- Uppsala universitet,Materialteori
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- Hussain, Tahziba (författare)
- ICMR Reg Med Res Ctr, Div Microbiol, Bhubaneswar 751023, Odisha, India.;ICMR Reg Med Res Ctr, NCDs, Bhubaneswar 751023, Odisha, India
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- Pati, Sanghamitra (författare)
- ICMR Reg Med Res Ctr, Div Publ Hlth & Res, Bhubaneswar, Odisha, India
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ICMR Reg Med Res Ctr, Div Microbiol, Bhubaneswar 751023, Odisha, India;ICMR Reg Med Res Ctr, NCDs, Bhubaneswar 751023, Odisha, India Pondicherry Univ, Dept Bioinformat, Pondicherry, India (creator_code:org_t)
- 2022-04-13
- 2022
- Engelska.
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Ingår i: Proteins. - : John Wiley & Sons. - 0887-3585 .- 1097-0134. ; 90:9, s. 1617-1633
- Relaterad länk:
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https://onlinelibrar...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with the most contagious variants, alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and Omicron (B.1.1.529) has continuously added a higher number of morbidity and mortality, globally. The present integrated bioinformatics-cheminformatics approach was employed to locate potent antiviral marine alkaloids that could be used against SARS-CoV-2. Initially, 57 antiviral marine alkaloids and two repurposing drugs were selected from an extensive literature review. Then, the putative target enzyme SARS-CoV-2 main protease (SARS-CoV-2-Mpro) was retrieved from the protein data bank and carried out a virtual screening-cum-molecular docking study with all candidates using PyRx 0.8 and AutoDock 4.2 software. Further, the molecular dynamics (MD) simulation of the two most potential alkaloids and a drug docking complex at 100 ns (with two ligand topology files from PRODRG and ATB server, separately), the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy, and contributions of entropy were investigated. Then, the physicochemical-toxicity-pharmacokinetics-drug-likeness profiles, the frontier molecular orbitals energies (highest occupied molecular orbital, lowest unoccupied molecular orbital, and Delta E), and structural-activity relationship were assessed and analyzed. Based on binding energy, 8-hydroxymanzamine (-10.5 kcal/mol) and manzamine A (-10.1 kcal/mol) from all alkaloids with darunavir (-7.9 kcal/mol) and lopinavir (-7.4 kcal/mol) against SARS-CoV-2-Mpro were recorded. The MD simulation (RMSD, RMSF, Rg, H-bond, MM/PBSA binding energy) illustrated that the 8-hydroxymanzamine exhibits a static thermodynamic feature than the other two complexes. The predicted physicochemical, toxicity, pharmacokinetics, and drug-likeness profiles also revealed that the 8-hydroxymanzamine could be used as a potential lead candidate individually and/or synergistically with darunavir or lopinavir to combat SARS-CoV-2 infection after some pharmacological validation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- antiviral marine alkaloids
- drug-likeness profiles prediction
- molecular docking simulation
- severe acute respiratory syndrome coronavirus-2-Mpro
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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