Using Chou’s 5-steps rule to study pharmacophore-based virtual screening of SARS-CoV-2 Mpro inhibitors

Pundir, Hemlata; Joshi, Tanuja; Joshi, Tushar; Sharma, Priyanka; Mathpal, Shalini; Chandra, Subhash; Tamta, Sushma

doi:10.1007/s11030-020-10148-5

Cited by 13 publications

(4 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The average number of H‐bonds of the duplicate MDS run formed by the docked complexes p37‐2238 and p37‐1270 were calculated as 9.14 and 6.95, respectively (Figure 6e) and demonstrates that the peptides strongly bind with the receptor protein inside the dynamic environment. [ 68 ] Further, the binding residues that contributed to hydrogen bond formation in the MD simulation were compared with the H‐bond forming residues in the H‐Dock. We found interacting binding site residues of p37, such as Asp248, Asn250, Val284, Thr333, Leu239, and Asn312 are found in both cases, which implies the accuracy of the binding ability of lead peptides with p37.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

et al. 2023

View full text Add to dashboard Cite

Monkeypox is a zoonotic disease caused by the Poxviridiea family virus Monkeypox. According to the Centers for Disease Control and Prevention, 70,420 monkeypox virus infections had been reported in 107 countries as of October 6, 2022. New studies have concluded that the monkeypox outbreak is caused by a strain with a unique mutation, increasing the possibility that the virus may develop resistance to current medicines by accumulating mutations in therapeutic targets. As peptide‐based therapeutics impede the drug target through multiple interactions, it may offer a better therapeutic solution to the possible drug resistance issue related to monkeypox treatment. Therefore, in this work, we screened an antiviral peptide library, the CPP site 2.0 database, against the p37 target protein using molecular docking approaches. The p37 is required for the viral pathogen's successful egression and spread. The allergenicity and physicochemical properties of the peptides were thoroughly analyzed before the molecular docking studies for selecting druggable candidates. The interactions of the peptides bearing the highest docking score were validated further by using molecular dynamics (MD) simulation studies. Our investigation revealed that two cell‐penetrating peptides of the CPP site 2.0 database might effectively prevent the egression and spread of the MPXV by inhibiting p37. Following more testing, these peptides can be explored in developing peptide‐based therapies against the MPX therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

“…and demonstrates that the peptides strongly bind with the receptor protein inside the dynamic environment. [68] Further, the binding residues that contributed to hydrogen bond formation in the MD simulation were compared with the H-bond forming residues in the H-Dock.…”

Section: Molecular Dynamic Simulation Of the Potent Peptides In Compl...mentioning

confidence: 99%

An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

et al. 2023

View full text Add to dashboard Cite

show abstract

“…A molecular docking approach reveals the binding affinity of the individual ligand to a specific target protein structure to assist rational drug design (Jones and Willett 1995 ). Understanding the interaction dynamics and possible binding mechanisms will facilitate the discovery of strong protein inhibitors (Liu et al 2018 ; Patel et al 2019 ). Using the HDOCK server, we evaluated the binding affinities, interactions between the query peptide sequences from AVPdb and HIPdb, and the amino acid residues of omicron RBD crucial for interaction with hACE2.…”

Section: Resultsmentioning

confidence: 99%

Identification of antiviral peptide inhibitors for receptor binding domain of SARS-CoV-2 omicron and its sub-variants: an in-silico approach

et al. 2022

View full text Add to dashboard Cite

Omicron, a variant of concern (VOC) of SARS-CoV-2, emerged in South Africa in November 2021. Omicron has been continuously acquiring a series of new mutations, especially in the spike (S) protein that led to high infectivity and transmissibility. Peptides targeting the receptor-binding domain (RBD) of the spike protein by which omicron and its variants attach to the host receptor, angiotensin-converting enzyme (ACE2) can block the viral infection at the first step. This study aims to identify antiviral peptides from the Antiviral peptide database (AVPdb) and HIV-inhibitory peptide database (HIPdb) against the RBD of omicron by using a molecular docking approach. The lead RBD binder peptides obtained through molecular docking were screened for allergenicity and physicochemical criteria (isoelectric point (pI) and net charge) required for peptide-based drugs. The binding affinity of the best five peptide inhibitors with the RBD of omicron was validated further by molecular dynamics (MD) simulation. Our result introduces five antiviral peptides, including AVP1056, AVP1059, AVP1225, AVP1801, and HIP755, that may effectively hinder omicron-host interactions. It is worth mentioning that all the three major sub-variants of omicron, BA.1 (B.1.1.529.1), BA.2 (B.1.1.529.2), and BA.3 (B.1.1.529.3), exhibits conserved ACE-2 interacting residues. Hence, the screened antiviral peptides with similar affinity can also interrupt the RBD-mediated invasion of different major sub-variants of omicron. Altogether, these peptides can be considered in the peptide-based therapeutics development for omicron treatment after further experimentation. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03258-4.

show abstract

“…Additionally, we believe that these results should be followed by in vitro and in vivo studies. In response to the COVID-19 pandemic, scientists applied various in silico approaches to analyze SARS-CoV-2 structures [ 38 ], study potential natural inhibitors [ 39 ], introduce new drug targets [ 40 ], design and optimize the structures of peptide-mimetic inhibitors [ 41 ], design SARS-CoV-2 vaccines [ 42 ], and repurpose FDA-approved or previously known drugs [ 43 ]. Our team used various in silico approaches to discover a potential natural inhibitor.…”

Section: Introductionmentioning

confidence: 99%

A Multistage In Silico Study of Natural Potential Inhibitors Targeting SARS-CoV-2 Main Protease

Elkaeed

Eissa

Elkady

et al. 2022

IJMS

View full text Add to dashboard Cite

Among a group of 310 natural antiviral natural metabolites, our team identified three compounds as the most potent natural inhibitors against the SARS-CoV-2 main protease (PDB ID: 5R84), Mpro. The identified compounds are sattazolin and caprolactin A and B. A validated multistage in silico study was conducted using several techniques. First, the molecular structures of the selected metabolites were compared with that of GWS, the co-crystallized ligand of Mpro, in a structural similarity study. The aim of this study was to determine the thirty most similar metabolites (10%) that may bind to the Mpro similar to GWS. Then, molecular docking against Mpro and pharmacophore studies led to the choice of five metabolites that exhibited good binding modes against the Mpro and good fit values against the generated pharmacophore model. Among them, three metabolites were chosen according to ADMET studies. The most promising Mpro inhibitor was determined by toxicity and DFT studies to be caprolactin A (292). Finally, molecular dynamics (MD) simulation studies were performed for caprolactin A to confirm the obtained results and understand the thermodynamic characteristics of the binding. It is hoped that the accomplished results could represent a positive step in the battle against COVID-19 through further in vitro and in vivo studies on the selected compounds.

show abstract

Using Chou’s 5-steps rule to study pharmacophore-based virtual screening of SARS-CoV-2 Mpro inhibitors

Cited by 13 publications

References 39 publications

An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

Identification of antiviral peptide inhibitors for receptor binding domain of SARS-CoV-2 omicron and its sub-variants: an in-silico approach

A Multistage In Silico Study of Natural Potential Inhibitors Targeting SARS-CoV-2 Main Protease

Contact Info

Product

Resources

About