Targeting the initiation and termination codons of SARS-CoV-2 spike protein as possible therapy against COVID-19: the role of novel harpagide 5-O-β-D-glucopyranoside from Clerodendrum volubile P Beauv. (Labiatae)

Abstract

The global spread of the coronavirus infections disease − 2019 (COVID-19) and the search for new drugs from natural products particularly from plants are receiving much attention recently. In this study, the therapeutic potential of a new iridoid glycoside isolated from the leaves of Clerodendrum volubile against COVID-19 was investigated. Harpagide 5-O-β-D-glucopyranoside (HG) was isolated, characterised and investigated for its druglikeness, optimized geometry, and pharmacokinetics properties. Its immunomodulatory was determined by chemiluminescence assay using polymorphonuclear neutrophils (PMNs) in addition to T-cell proliferation assay. In silico analysis was used in determining its molecular interaction with severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). HG displayed potent druglikeness properties, with no inhibitory effect on cytochrome P₄₅₀ (1A2, 2C19, 2C9, 2D6 and 3A4) and a predicted LD₅₀ of 2000 mg/kg. Its ¹H-NMR chemical shifts showed a little deviation of 0.01 and 0.11 ppm for H-4 and H-9, respectively. HG significantly suppressed oxidative bursts in PMNs, while concomitantly inhibiting T-cell proliferation. It also displayed a very strong binding affinity with the translation initiation and termination sequence sites of spike (S) protein mRNA of SARS-COV-2, its gene product, and host ACE2 receptor. These results suggest the immunomodulatory properties and anti-SARS-COV-2 potentials of HG which can be explored in the treatment and management of COVID-19.

Communicated by Ramaswamy H. Sarma

Keywords:

• Clerodendrum volubile
• COVID-19
• harpagide 5-O-β-D-glucopyranoside
• SARS-COV-2
• and spike protein

Acknowledgements

OE acknowledges The World Academy of Science (TWAS) for 2012 ICCBS-TWAS fellowship at the H.E.J. Research Institute of Chemistry, ICCBS, University of Karachi, Karachi, Pakistan.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by The World Academy of Sciences.