LAPSE:2024.1312
Published Article
LAPSE:2024.1312
In Silico and In Vitro Analyses of Multiple Terpenes Predict Cryptotanshinone as a Potent Inhibitor of the Omicron Variant of SARS-CoV-2
Asmita Shrestha, Siddha Raj Upadhyaya, Bimal K. Raut, Salyan Bhattarai, Khaga Raj Sharma, Niranjan Parajuli, Jae Kyung Sohng, Bishnu P. Regmi
June 21, 2024
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) underwent a substantial number of alterations, and the accompanying structural mutations in the spike protein prompted questions about the virus’s propensity to evade the antibody neutralization produced by prior infection or vaccination. New mutations in SARS-CoV-2 have raised serious concerns regarding the effectiveness of drugs and vaccines against the virus; thus, identifying and developing potent antiviral medications is crucial to combat viral infections. In the present study, we conducted a detailed in silico investigation that involves molecular docking, density functional (DFT) analysis, molecular dynamics (MD) simulations, and pharmacological analysis followed by an in vitro study with the spike protein. Among fifty terpenes screened, cryptotanshinone and saikosaponin B2 were found to be potent S1-RBD spike protein inhibitors, displaying considerable hydrogen bond interactions with key binding site residues, significant binding affinity, and high reactivity attributed to band gap energy. In addition, 100 ns molecular dynamics (MD) simulations further substantiated these findings, showcasing the stability of the compounds within a biological environment. With favorable pharmacokinetic properties and a low half inhibitory concentration (IC50) of 86.06 ± 1.56 μM, cryptotanshinone inhibited S1-RBD of the SARS-CoV-2 Omicron variant. Our findings account for in-depth research on cryptotanshinone as a SARS-CoV-2 inhibitor.
Keywords
COVID-19, Omicron variant, spike protein, terpenes
Subject
Suggested Citation
Shrestha A, Upadhyaya SR, Raut BK, Bhattarai S, Sharma KR, Parajuli N, Sohng JK, Regmi BP. In Silico and In Vitro Analyses of Multiple Terpenes Predict Cryptotanshinone as a Potent Inhibitor of the Omicron Variant of SARS-CoV-2. (2024). LAPSE:2024.1312
Author Affiliations
Shrestha A: Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu 44618, Nepal [ORCID]
Upadhyaya SR: Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu 44618, Nepal
Raut BK: Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu 44618, Nepal
Bhattarai S: Paraza Pharma, Inc., 2525 Avenue Marie-Curie, Montreal, QC H4S 2E1, Canada
Sharma KR: Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu 44618, Nepal
Parajuli N: Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu 44618, Nepal; Institute of Biomolecule Reconstruction (iBR), Department of Life Science and Biochemical Engineering, Sun Moon University, Asan 31460, Republic of Korea [ORCID]
Sohng JK: Institute of Biomolecule Reconstruction (iBR), Department of Life Science and Biochemical Engineering, Sun Moon University, Asan 31460, Republic of Korea [ORCID]
Regmi BP: Department of Chemistry, Florida Agricultural and Mechanical University, Tallahassee, FL 32307, USA [ORCID]
Journal Name
Processes
Volume
12
Issue
1
First Page
230
Year
2024
Publication Date
2024-01-21
Published Version
ISSN
2227-9717
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PII: pr12010230, Publication Type: Journal Article
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LAPSE:2024.1312
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doi:10.3390/pr12010230
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Jun 21, 2024
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