Theoretical Study on Modified Boceprevir Compounds as NS3 Protease Inhibitors

Saleh, Noha A.; Ezat, Ahmed A.; Elfiky, Abdo A.; Elshemey, Wael M.; Ibrahim, Medhat

doi:10.1166/jctn.2015.3738

Cited by 15 publications

(14 citation statements)

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“…Molecular docking (MD) is important in testing the binding of small molecules to protein active site and in virtual screening . These in silico techniques were used to study viral proteins . Molecular dynamics simulation (MDS) offers a means to study protein dynamics in silico.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulation revealed binding of nucleotide inhibitors to ZIKV polymerase over 444 nanoseconds

Elfiky

Elshemey

2017

Journal of Medical Virology

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In the year 2015, new Zika virus (ZIKV) broke out in Brazil and spread away in more than 80 countries. Scientists directed their efforts toward viral polymerase in attempt to find inhibitors that might interfere with its function. In this study, molecular dynamics simulation (MDS) was performed over 444 ns for a ZIKV polymerase model. Molecular docking (MD) was then performed every 10 ns during the MDS course to ensure the binding of small molecules to the polymerase over the entire time of the simulation. MD revealed the binding ability of four suggested guanosine inhibitors (GIs); (Guanosine substituted with OH and SH (phenyl) oxidanyl in the 2' carbon of the ribose ring). The GIs were compared to guanosine triphosphate (GTP) and five anti-hepatitis C virus drugs (either approved or under clinical trials). The mode of binding and the binding performance of GIs to ZIKV polymerase were found to be the same as GTP. Hence, these compounds were capable of competing GTP for the active site. Moreover, GIs bound to ZIKV active site more tightly compared to ribavirin, the wide-range antiviral drug.

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Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulation revealed binding of nucleotide inhibitors to ZIKV polymerase over 444 nanoseconds

Elfiky

Elshemey

2017

Journal of Medical Virology

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“…MERS CoV PL pro is a multifunctional cysteine protease that processes both viral polyprotein and some host-cell proteins by hydrolyzing the peptide and isopeptide bonds in the substrates [38]. In order to perform this function, a conserved active site triad is required [20,23,39,40]. C111, H278, and D293 are reported to be the active site triad residues in MERS CoV PL pro [1,2].…”

Section: Discussionmentioning

confidence: 99%

Drug repurposing against MERS CoV and SARS-COV-2 PLpro in silico

Elfiky

Ibrahim

Elshemey

2020

Preprint

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Aim: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) and COVID-19 cause severe acute, deadly, pneumonia. Papain-like protease (PLpro), is HCoV cysteine protease encoded within the Non-Structural protein 3. Materials and Methods: Molecular docking is performed to test the binding performance of six protease inhibitors against MERS CoV and SARS-CoV-2 PLpro. Results: The compound, GRL-0667, shows the highest binding affinity to MERS CoV PLpro, while Grazoprevir shows the highest binding affinity against HCV NS3. Moreover, the interaction pattern in the case of HCV NS3 is the same as in the case of coronaviruses. Conclusion: The present study shows the ability of some anti-SARS CoV and anti-HCV NS3 drugs to inhibit MERS CoV PLpro, interestingly, including the newly emerged SARS-COV-2 PLpro.

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“…It helps reduce time, money, and effort in the journey of drug design [ 27 ]. It was successful in helping find potent anti-viral agents against many viruses, like Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) [ 28 , 29 , 30 ]. Additionally, computer-aided drug design is used to find the potency of drugs and natural products against SARS-CoV-2 proteins during the last few months [ 31 , 32 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (Mpro)

et al. 2020

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A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (Mpro) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds 3a, 3b, and 3c (–8.1 ± 0.33 kcal/mol, –8.0 ± 0.35 kcal/mol, and –8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (–6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.

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Theoretical Study on Modified Boceprevir Compounds as NS3 Protease Inhibitors

Cited by 15 publications

References 0 publications

Molecular dynamics simulation revealed binding of nucleotide inhibitors to ZIKV polymerase over 444 nanoseconds

Molecular dynamics simulation revealed binding of nucleotide inhibitors to ZIKV polymerase over 444 nanoseconds

Drug repurposing against MERS CoV and SARS-COV-2 PLpro in silico

Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (Mpro)

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