Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures

Kumar, Durgesh; Kumari, Kamlesh; Jayaraj, Abhilash; Kumar, Vinod; Kumar, Ramappa Venkatesh; Dass, Sujata K.; Chandra, Ramesh; Singh, Prashant

doi:10.1080/07391102.2020.1752310

Cited by 91 publications

(83 citation statements)

References 48 publications

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“…Among them two crucial proteases such as main protease (Mpro) and papain-like protease (PLpro) are vital for virus replication 22 , 23 , 24 . Meanwhile, a tremendous effort has been spent on studying these proteases in order to discover specific inhibitors against this noxious COVID-19 25- 30 .…”

Section: Introductionmentioning

confidence: 99%

Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors

Amin

Banerjee

Ghosh

et al. 2021

Bioorganic & Medicinal Chemistry

160

118

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Section: Introductionmentioning

confidence: 99%

Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors

Amin

Banerjee

Ghosh

et al. 2021

Bioorganic & Medicinal Chemistry

160

118

View full text Add to dashboard Cite

show abstract

“…Another co-crystal (PDB-ID 6Y2F/6Y2G), a-ketoamide inhibitor (13b) is also reported recently, providing the structural and residue-based architecture of catalytic sites . These co-crystals are paving the route for the application of virtual screening (VS) to get more efficacious molecules (Al-Khafaji et al, 2020;Kumar et al, 2020;Lobo-Galo et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach

Mittal

Kumari

Srivastava

et al. 2020

Journal of Biomolecular Structure and Dynamics

170

106

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The pandemic caused by novel coronavirus disease 2019 infecting millions of populations worldwide and counting, has demanded quick and potential therapeutic strategies. Current approved drugs or molecules under clinical trials can be a good pool for repurposing through in-silico techniques to quickly identify promising drug candidates. The structural information of recently released crystal structures of main protease (M pro ) in APO and complex with inhibitors, N3, and 13b molecules was utilized to explore the binding site architecture through Molecular dynamics (MD) simulations. The stable state of M pro was used to conduct extensive virtual screening of the aforementioned drug pool. Considering the recent success of HIV protease molecules, we also used anti-protease molecules for drug repurposing purposes. The identified top hits were further evaluated through MD simulations followed by the binding free energy calculations using MM-GBSA. Interestingly, in our screening, several promising drugs stand out as potential inhibitors of M pro . However, based on control (N3 and 13b), we have identified six potential molecules, Leupeptin Hemisulphate, Pepstatin A, Nelfinavir, Birinapant, Lypression and Octreotide which have shown the reasonably significant MM-GBSA score. Further insight shows that the molecules form stable interactions with hot-spot residues, that are mainly conserved and can be targeted for structure-and pharmacophore-based designing. The pharmacokinetic annotations and therapeutic importance have suggested that these molecules possess drug-like properties and pave their way for in-vitro studies. ARTICLE HISTORY

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“…These residues contribute energy is due to different interactions like hydrogen bonding, van der Waals, electrostatic interactions, π-π stacking, etc. [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

In silico Investigation on the Inhibiting Role of Nicotine/Caffeine by Blocking the S Protein of SARS-CoV-2 Versus ACE2 Receptor

et al. 2020

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In this paper, we studied the in silico interaction of angiotensin-converting enzyme 2 (ACE2) human receptor with two bioactive compounds, i.e., nicotine and caffeine, via molecular dynamic (MD) simulations. The simulations reveal the efficient blocking of ACE2 by caffeine and nicotine in the exposure to the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have selected the two most important active sites of ACE2-S protein, i.e., 6LZG and 6VW1, which are critically responsible in the interaction of S protein to the receptor and thus, we investigated their interaction with nicotine and caffeine through MD simulations. Caffeine and nicotine are interesting structures for interactions because of their similar structure to the candidate antiviral drugs. Our results reveal that caffeine or nicotine in a specific molar ratio to 6LZG shows a very strong interaction and indicate that caffeine is more efficient in the interaction with 6LZG and further blocking of this site against S protein binding. Further, we investigated the interaction of ACE2 receptor- S protein with nicotine or caffeine when mixed with candidate or approved antiviral drugs for SARS-CoV-2 therapy. Our MD simulations suggest that the combination of caffeine with ribavirin shows a stronger interaction with 6VW1, while in case of favipiravir+nicotine, 6LZG shows potent efficacy of these interaction, proposing the potent efficacy of these combinations for blocking ACE2 receptor against SARS-CoV-2.

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Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures

Cited by 91 publications

References 48 publications

Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors

Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors

Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach

In silico Investigation on the Inhibiting Role of Nicotine/Caffeine by Blocking the S Protein of SARS-CoV-2 Versus ACE2 Receptor

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