Characterization of Phytochemical Inhibitors of the COVID-19 Primary Protease Using Molecular Modelling Approach
Sunita, Gohar Taj
Asian Journal of Microbiology and Biotechnology, doi:10.56557/ajmab/2024/v9i28800
The objective of this research is to find an antiviral medication that would work against the SARS-CoV-2 virus. Using existing effective pharmaceuticals from various virus treatments will be an immediate qualifying strategy. Virtual screening of antiviral databases for possible therapeutic effect were used to identify favourable pharmacological compounds. In anti-CoV medication development, targeting the major protease (pdb id: 6LU7) is becoming more significant. This paper focuses on the In silico evaluation of proposed anti-Alzheimer activity. Including toxicity prediction, molinspiration, AdmetSAR predictions, and targeted docking investigations, the best therapeutic candidates have been offered. Based on Viber and Lipinski rules, 4 derivatives were chosen for bioactivity prediction and drug similarity score. The reference standard drugs for the comparison of molecular descriptors
DISCUSSION The main purpose of the computational screening approach is to extract potential drug candidates from synthetic library services. The SARS-primary CoV-2 protease was targeted by compounds from Cichorium intybus in the current study. Fig. 1 shows the process flow for the computational work. Because of its crucial function in the processing of viral polyproteins and viral maturation inside the infected host cells, the SARS-primary CoV-2 protease is a class of viral protease that is thought to be a functional therapeutic target protein. Four bioactive substances were initially subjected to molecular docking analysis in the blind docking mode. The improvement of forecasting (Table 4 ). The lead bioactive candidates' molecular docking outcomes were contrasted with those of hydrochloroquine and remdesivir. A recent SARS-primary CoV-2 protease infection is one that is treated with remdesivir and hydrochloroquine. The binding mode and type of interactions are consistent with earlier reported molecular docking studies of antiviral drugs. In comparison to all other bioactive compounds, hydrocholroquine and remdesivir had higher binding energies (-4.52 kcal/mol and
COMPETING INTERESTS Authors have declared that no competing interests exist.
References
Ahmed, Mahtarin, Ahmed, Akter, Islam et al., Investigating the binding affinity, interaction, and structure-activityrelationship of 76 prescription antiviral drugs targeting RdRp and Mpro of SARS-CoV-2, Journal of Biomolecular Structure and Dynamics
Augustin, Kuzina, Andersen, Bak, Molecular activities, biosynthesis and evolution of triterpenoid saponins, Phytochemistry
Benet, Hosey, Ursu, Oprea, BDDCS, the Rule of 5 and drugability, Advanced drug delivery reviews
Bickerton, Paolini, Besnard, Muresan, Hopkins, Quantifying the chemical beauty of drugs, Nature chemistry
Cui, Li, Shi, Origin and evolution of pathogenic coronaviruses, Nature reviews microbiology
Grinter, Zou, Challenges, applications, and recent advances of protein-ligand docking in structure-based drug design, Molecules
Huang, Yang, Xu, Xu, Liu, Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19, Acta Pharmacologica Sinica
John, Tomar, Stauffer, Mesecar, Targeting zoonotic viruses: Structurebased inhibition of the 3C-like protease from bat coronavirus HKU4-The likely reservoir host to the human coronavirus that causes Middle East Respiratory Syndrome (MERS), Bioorganic & medicinal chemistry
Lakshmanan, Murugesan, Rajendran, Ravichandran, Elangovan et al., leaves alleviate adjuvant-induced rheumatoid arthritis in rats via modulating the finest disease targets-IL2RA, IL18 and VEGFA, Journal of Biomolecular Structure and Dynamics
Lipinski, Lead-and drug-like compounds: the rule-of-five revolution, Drug discovery today: Technologies
Lu, Zhao, Li, Niu, Yang et al., Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding, The lancet
Muralidharan, Sakthivel, Velmurugan, Gromiha, Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 protease against COVID-19, Journal of Biomolecular Structure and Dynamics
Naik, Munikumar, Ramakrishna, Srujana, Goudar et al., Remdesivir (GS-5734) as a therapeutic option of 2019-nCOV main protease-in silico approach, Journal of Biomolecular Structure and Dynamics
Pires, Blundell, Ascher, pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures, Journal of medicinal chemistry
Schneider, Prediction of drug-like properties
Selvakumar, Palanichamy, Arumugam, Venkatesan, Aathmanathan et al., In silico potential of nutraceutical plant of Pithecellobium dulce against GRP78 target protein for breast cancer, Applied Nanoscience
Smith, Smith, Repurposing therapeutics for COVID-19: supercomputer-based docking to the SARS-CoV-2 viral spike protein and viral spike protein-human ACE2 interface
Wit, Van Doremalen, Falzarano, Munster, SARS and MERS: recent insights into emerging coronaviruses, Nature Reviews Microbiology
Yoo, Kim, Nam, Lee, Discovering health benefits of phytochemicals with integrated analysis of the molecular network, chemical properties and ethnopharmacological evidence, Nutrients
Zhou, Yang, Wang, Hu, Zhang et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature
{ 'indexed': {'date-parts': [[2024, 8, 3]], 'date-time': '2024-08-03T00:31:37Z', 'timestamp': 1722645097708},
'reference-count': 0,
'publisher': 'IK Press',
'issue': '2',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'abstract': '<jats:p>The objective of this research is to find an antiviral medication that would work '
'against the SARS-CoV-2 virus. Using existing effective pharmaceuticals from various virus '
'treatments will be an immediate qualifying strategy. Virtual screening of antiviral databases '
'for possible therapeutic effect were used to identify favourable pharmacological compounds. '
'In anti-CoV medication development, targeting the major protease (pdb id: 6LU7) is becoming '
'more significant. This paper focuses on the In silico evaluation of proposed anti-Alzheimer '
'activity. Including toxicity prediction, molinspiration, AdmetSAR predictions, and targeted '
'docking investigations, the best therapeutic candidates have been offered. Based on Viber and '
'Lipinski rules, 4 derivatives were chosen for bioactivity prediction and drug similarity '
'score. The reference standard drugs for the comparison of molecular descriptors and docking '
'were hydrochloroquine and remdesivir. Remdesivir is a well-known FDA-approved drug that slows '
'viral reproduction by terminating its binding to the viral RNA-dependent RNA polymerase. Our '
'proposed compounds share similarities with Remdesivir, and doxorubicin is another drug with '
'anti- SARS-CoV-2 virus. For pharmacological targets including such enzymes, nuclear '
'receptors, kinase inhibitors, G protein-coupled receptor (GPCR) ligands, and ion channel '
'modulators, the bioactivity score of the compounds was predicted Apart from 4\xa0compound, '
'which has been found to get AdmetSAR toxicity or impact, all proposed compounds showed good '
'blood-brain barrier (BBB) penetration, human intestinal absorption (HIA), and Caco-2 cell '
'permeability in their ADMET predictions. Rutin and quercetin have a strong affinity to '
'inhibit these proteins which cause SARS-CoV-2 virus. Our data provide evidence that therapy '
'is effective and enhances oral bioavailability.</jats:p>',
'DOI': '10.56557/ajmab/2024/v9i28800',
'type': 'journal-article',
'created': {'date-parts': [[2024, 8, 2]], 'date-time': '2024-08-02T04:12:15Z', 'timestamp': 1722571935000},
'page': '60-69',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Characterization of Phytochemical Inhibitors of the COVID-19 Primary Protease Using Molecular '
'Modelling Approach',
'prefix': '10.56557',
'volume': '9',
'author': [ {'family': 'Sunita', 'sequence': 'first', 'affiliation': []},
{'given': 'Gohar', 'family': 'Taj', 'sequence': 'additional', 'affiliation': []}],
'member': '35829',
'published-online': {'date-parts': [[2024, 8, 1]]},
'container-title': 'Asian Journal of Microbiology and Biotechnology',
'original-title': [],
'link': [ { 'URL': 'https://ikprress.org/index.php/AJMAB/article/download/8800/8178',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://ikprress.org/index.php/AJMAB/article/download/8800/8179',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://ikprress.org/index.php/AJMAB/article/download/8800/8180',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://ikprress.org/index.php/AJMAB/article/download/8800/8178',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2024, 8, 2]],
'date-time': '2024-08-02T04:12:16Z',
'timestamp': 1722571936000},
'score': 1,
'resource': {'primary': {'URL': 'https://ikprress.org/index.php/AJMAB/article/view/8800'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2024, 8, 1]]},
'references-count': 0,
'journal-issue': {'issue': '2', 'published-online': {'date-parts': [[2024, 5, 16]]}},
'URL': 'http://dx.doi.org/10.56557/ajmab/2024/v9i28800',
'relation': {},
'ISSN': ['2456-8341'],
'subject': [],
'container-title-short': 'Asian J. Microb. Biotech.',
'published': {'date-parts': [[2024, 8, 1]]}}
