Abstract
Plant-derived phytochemicals from medicinal plants are becoming increasingly attractive natural sources of antimicrobial and antiviral agents due to their therapeutic value, mechanism of action, level of toxicity and bioavailability. The continued emergence of more immune-evasive strains and the rate of resistance to current antiviral drugs have created a need to identify new antiviral agents against SARS-CoV-2. This study investigated the antiviral potential of balsaminol, a bioactive compound from Momordica balsamina, and its inhibitory activities against SARS-CoV-2 receptor proteins. In this study, three Food and Drug Administration (FDA) COVID-19 approved drugs namely; nirmatrelvir, ritonavir and remdesivir were used as positive control. Molecular docking was performed to determine the predominant binding mode (most negative Gibbs free energy of binding/ΔG) and inhibitory activity of balsaminol against SARS-CoV-2 receptor proteins. The pharmacokinetics, toxicity, physicochemical and drug-like properties of balsaminol were evaluated to determine its potential as an active oral drug candidate as well as its non-toxicity in humans. The results show that balsaminol E has the highest binding affinity to the SARS CoV-2 papain-like protease (7CMD) with a free binding energy of − 8.7 kcal/mol, followed by balsaminol A interacting with the spike receptor binding domain (6VW1) with − 8.5 kcal/mol and balsaminol C had a binding energy of − 8.1 kcal/mol with the main protease (6LU7) comparable to the standard drugs namely ritonavir, nirmatrelvir and remdesivir. However, the ADMET and drug-like profile of balsaminol F favours it as a better potential drug candidate and inhibitor of the docked SARS-CoV-2 receptor proteins. Further preclinical studies are therefore recommended.
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Abbreviations
- ADMET:
-
Absorption: distribution: metabolism: excretion: toxicity
- ACE2:
-
Angiotensin-converting enzyme 2
- COVID-19:
-
Coronavirus diseases 19
- 3CLpro:
-
3 Cysteine-like proteinase
- ChEMBL:
-
Chemical biology database European molecular biology laboratory
- CYP:
-
Cytochrome P
- E:
-
Envelope
- FDA:
-
Food and drug administration
- GDT:
-
Global distance test
- HBAs:
-
Hydrogen bond acceptors
- HBD:
-
Hydrogen bond donor
- ISG15:
-
Interferon stimulated gene 15
- N3:
-
N-[(5-METHYLISOXAZOL-3-YL)CARBONYL]ALANYL-L-VALYL-N ~ 1 ~ -((1R,2Z)-4-(BENZYLOXY)-4-OXO-1-{[(3R)-2-OXOPYRROLIDIN-3 YL]METHYL}BUT-2-ENYL)-L-LEUCINAMIDE
- NAG:
-
2-Acetamido-2-deoxy-beta-D-glucopyranose
- NAG:
-
N: Nucleocapsid protein
- Mpro:
-
Main proteinase
- M:
-
Membrane
- mRNAs:
-
Messenger ribonucleic acids
- MAVS:
-
Mitochondrial antiviral-signaling protein
- MW:
-
Molecular weights
- nsp:
-
Nonstructural proteins
- + ssRNA:
-
Positive single stranded RNA
- PLpro:
-
Papain-like protease
- pp:
-
Polyproteins
- PDB:
-
Protein Data Bank
- PubChem:
-
Chemical information database
- QMEAN:
-
Qualitative model energy analysis
- QSQE:
-
Quaternary structure quality estimate
- RBD:
-
Receptor binding domain
- RNA:
-
Ribonucleic acids
- RTC:
-
Replication-transcription complex
- RIG-I:
-
Retinoic acid-inducible gene I
- RMSD:
-
Root mean standard deviation
- RCSB:
-
Research collaborator for bioinformatics
- SARS-CoV-2:
-
Severe acute respiratory syndrome coronavirus 2
- S:
-
Spike
- ssRNA:
-
Single stranded RNA
- sgRNAs:
-
Single guide RNA
- SMILES:
-
Simplified molecular input line entry system
- SDF:
-
Structural data file
- SVM:
-
Support vector machines
- TTT:
-
5-Amino-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide
- TPSA:
-
Topological polar surface area
- TMPRSS2:
-
Transmembrane protease serine 2
- VOC:
-
Variant of concern
- VUM:
-
Variant under monitoring
- WHO:
-
World Health Organization
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This article is dedicated to all the research scientists and healthcare workers across the world that had contributed in vaccine development, drug design and development.
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DDG, AM, JSM and RA designed the research, performed virtual screening. DDG, AM, JSM, RA, AJD, ROB, MH, SSE, RIO, MS revised the manuscript. DDG, AM, JSM and RA performed the bioinformatics analysis, molecular dynamics simulation, analyzed the virtual screening experiment data and drafted the manuscript. All authors have read and approved the final manuscript.
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Gaiya, D.D., Muhammad, A., Musa, J.S. et al. In silico analysis of balsaminol as anti-viral agents targeting SARS-CoV-2 main protease, spike receptor binding domain and papain-like protease receptors. In Silico Pharmacol. 12, 75 (2024). https://doi.org/10.1007/s40203-024-00241-0
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DOI: https://doi.org/10.1007/s40203-024-00241-0
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