Ginkgo terpenoid against COVID-19

Due to the reported high ability of virulence of COVID_19 in recent months, several studies have been conducted to discover and introduce COVID_19 antiviral drugs. The results of numerous studies have shown that protease inhibitors and compounds, which make up the major part of plant derivatives, especially terpenoids, can therefore be very effective in controlling virus-induced infection. A recent paper in ChemRxiv reported on the bioinformatical study of COVID_19 inhibition by terpenoids of plant origin [1].

Terpenoids are the major secondary plant constituents, with numerous medicinal properties including anti-cancer,  anti-oxidant, anti inflammatory, antiviral, and antibacterial. Using the structure of terpene comounds and COVID_19 protease received from the databases such as PubChem and Protein Data Bank (PDB) molecular docking was performed by MVD (molegro virtual docker) software.

The investigated terpenoids can interfere with the important amino acids in the enzymatic cavity to inhibit the protease enzyme of the virus. Nine neutral drugs, namely, Thymoquinone, Salvinorin A, Bilobalide, Citral, Menthol, Ginkgolide A, Noscapine, Forscolin, Beta Selinene were identified to have inhibitory activities against novel COVID-19 protease. Of these compounds, Ginkgolide A has the strongest bond and highest affinity with protease.

Ginkgolides (Table 1) are familiar for the cyclodextrin researchers. They interact with cyclodextrins making possible their separation from other diterpene lactones by electrokinetic chromatography [2].  Ginkgolides can be solubilized by gamma-cyclodextrin [3] and hydroxypropyl-beta-cyclodextrin [4] to get formulations for injection.

Table 1 Gingkolides compounds

[1] Shaghaghi, N (2020): Molecular Docking Study of Novel COVID-19 Protease with Low Risk Terpenoides Compounds of Plants. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.11935722.v1

[2] Dubber, M.-J., Kanfer, I. (2006)Application of reverse-flow micellar electrokinetic chromatography for the simultaneous determination of flavonols and terpene trilactones in Ginkgo biloba dosage forms. Journal of Chromatography, A, 1122(1-2), 266-274

[3] Defaye, J.; Laine, V.; Djedaini-Pilard, F.; Perly, B. (1997) Use of cyclodextrins and their derivatives for solubilising compounds of the Ginkgolide family. Eur. Pat. Appl. EP 764659

Cao, Q., Lou, F., Ding, F. (2005) Process for extracting ginkgolide, ginkgolide injection and process for preparing same. Chinese Pat. Appl. CN1594319