Pharmacophore based virtual screening for natural product database revealed possible inhibitors for SARS-COV-2 main protease

El-Ashrey, Mohamed K.; Bakr, Riham O.; Fayed, Marwa A. A.; Refaey, Rana H.; Nissan, Yassin M.

doi:10.1016/j.virol.2022.03.003

Cited by 5 publications

(7 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ZINCPHARMER is one of the web-based platforms for virtual screening for the pharmacophore against the ZINC drug database. Molecules with low root mean square deviation (RMSD) values from the active sites of pharmacophores were chosen for docking studies from the various hit compounds displayed by the ZINC database [ 7 ]. Compounds with low RMSD values are preferred because they are highly structurally similar to the pharmacophore's active sites.…”

Section: Discussionmentioning

confidence: 99%

“…Molecules with the lowest RMSD values, 0.145 or lower, were chosen for docking studies. The lower the RMSD value of a molecule, the lower its structural deviation from the pharmacophore's active sites [ 7 ]. Therefore, low RMSD values denote a molecule's high structural similarity to the pharmacophore's active sites.…”

Section: Discussionmentioning

confidence: 99%

“…It causes infection by interacting with receptors and transmembrane proteases on the cell membrane of the host. El-Ashrey et al [ 7 ] and Hoffmann et al [ 8 ] point out that the virus interacts with angiotensin-converting enzyme 2 (ACE2) transmembrane protease and receptor serine 2 (TMPRSS2) to cause infection.…”

Section: Introductionmentioning

confidence: 99%

“…SARS-Cov-2 M pro is among the integral targets for COVID 19 drug production since its maturation and that of other important polyproteins after the viral spike protein binds to angiotensin-converting enzyme 2 (ACE2) receptor lead to the virus's entry into the host cell and subsequent COVID 19 infection. It is essential for the virus's proteolytic development [ 7 ]. It is thought to be a probable target for diminishing the spread of the illness by blocking the active areas of viral polyprotein cleavage [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is essential for the virus's proteolytic development [ 7 ]. It is thought to be a probable target for diminishing the spread of the illness by blocking the active areas of viral polyprotein cleavage [ 7 ]. M pro 's sequence and structure are very similar to those of other beta coronaviruses.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening

Onyango

Odhiambo

Angwenyi

et al. 2022

Journal of Tropical Medicine

View full text Add to dashboard Cite

Infectious agents such as SARS-CoV, MERS-CoV, and SARS-CoV-2 have emerged in recent years causing epidemics with high mortality rates. The quick development of novel therapeutic compounds is required in the fight against such pathogenic agents. Unfortunately, the traditional drug development methods are time-consuming and expensive. In this study, computational algorithms were utilized for virtual screening of a library of natural compounds in the ZINC database for their affinity towards SARS-CoV-2 Mpro. Compounds such as cinanserin, nelfinavir, baicalin, baicalein, candesartan cilexetil, chloroquine, dipyridamole, and hydroxychloroquine have the ability to prevent SARS-CoV-2 Mpro from facilitating COVID 19 infection; thus, they treat COVID 19. However, these drugs majorly act to reduce the symptoms of the disease. No anti-viral drug against COVID 19 virus infection has been discovered and approved. Therefore, this study sought to explore natural inhibitors of SARS-CoV-2 Mpro to develop a pharmacophore model for virtual screening of natural compounds in the ZINC database as potential candidates for SARS-CoV-2 Mpro inhibitors and as therapeutic molecules against COVID 19. This study undertook in silico methods to identify the best anti-viral candidates targeting SAR-CoV-2 Mpro from natural sources in the ZINC database. Initially, reported anti-SARS-CoV-2 Mpro molecules were integrated into designing a pharmacophore model utilizing PharmaGist. Later, the pharmacophore model was loaded into ZINCPHARMER and screened against the ZINC database to identify new probable drug candidates. The root means square deviation (RMSD) values of the potential drug candidates informed the selection of some of them, which were docked with SARS-CoV-2 Mpro to comprehend their interactions. From the molecular docking results, the top four candidates (ZINC000254823011, ZINC000072307130, ZINC000013627512, and ZINC000009418994) against SARS-CoV-2 Mpro, with binding energies ranging from –8.2 kcal/mol to –8.6 kcal/mol, were examined for their oral bioavailability and other pharmacokinetic properties. Consequently, ZINC000072307130 emerged as the only orally bioavailable drug candidate with desirable pharmacokinetic properties. This candidate drug was used to perform MD simulations, and the outcomes revealed that ZINC000072307130 formed a stable complex with the viral main protease. Consequently, ZINC000072307130 emerges as a potential anti-SARS-CoV-2 Mpro inhibitor for the production of new COVID 19 drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening

Onyango

Odhiambo

Angwenyi

et al. 2022

Journal of Tropical Medicine

View full text Add to dashboard Cite

show abstract

Activation of endoplasmic reticulum stress by harmine suppresses the growth of esophageal squamous cell carcinoma

Fan

Wang

et al. 2023

Phytotherapy Research

View full text Add to dashboard Cite

The worldwide overall 5‐year survival rate of esophageal squamous cell carcinoma (ESCC) patients is less than 20%, and novel therapeutic strategies for these patients are urgently needed. Harmine is a natural β‐carboline alkaloid, which received great interest in cancer research because of its biological and anti‐tumor activities. The aim of this study is to examine the effects of harmine on ESCC and its mechanism. We investigated the effects of harmine on proliferation, cell cycle, apoptosis, and tumor growth in vivo. RNA sequencing (RNA‐seq), real‐time PCR, and western blotting were used to detect the mechanism. Harmine inhibited ESCC cell growth in vitro and tumor growth in vivo. Differentially expressed genes in harmine‐treated ESCC cells were mainly involved in protein processing in the endoplasmic reticulum (ER). Real‐time PCR and western blotting confirmed harmine‐induced cellular ER stress. CRISPR‐Cas9 knockout of C/EBP homologous protein (CHOP) abolished harmine‐induced expression of death receptor 5 and apoptosis. Harmine also induced the expression of CHOP‐mediated sestrin‐2, which in turn contributes to autophagosome formation via suppressing the AMP‐activated protein kinase‐protein kinase B‐mammalian target of rapamycin signaling pathway. In conclusion, our results demonstrate that harmine inhibits the growth of ESCC through its regulation of ER stress, suggesting that it is a promising candidate for ESCC treatment.

show abstract

Synthesis, optical properties, DNA, β-cyclodextrin interaction, hydrogen isotope sensor and computational study of new enantiopure isoxazolidine derivative (ISoXD)

Alotayeq,

Ghannay,

Alhagri

et al. 2024

Heliyon

View full text Add to dashboard Cite

Pharmacophore based virtual screening for natural product database revealed possible inhibitors for SARS-COV-2 main protease

Cited by 5 publications

References 65 publications

In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening

In Silico Identification of New Anti-SARS-CoV-2 Main Protease (Mpro) Molecules with Pharmacokinetic Properties from Natural Sources Using Molecular Dynamics (MD) Simulations and Hierarchical Virtual Screening

Activation of endoplasmic reticulum stress by harmine suppresses the growth of esophageal squamous cell carcinoma

Synthesis, optical properties, DNA, β-cyclodextrin interaction, hydrogen isotope sensor and computational study of new enantiopure isoxazolidine derivative (ISoXD)

Contact Info

Product

Resources

About