Natural product-derived phytochemicals as potential agents against coronaviruses: A review

Abstract

Coronaviruses are responsible for a growing economic, social and mortality burden, as the causative agent of diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), avian infectious bronchitis virus (IBV) and COVID-19. However, there is a lack of effective antiviral agents for many coronavirus strains. Naturally existing compounds provide a wealth of chemical diversity, including antiviral activity, and thus may have utility as therapeutic agents against coronaviral infections. The PubMed database was searched for papers including the keywords coronavirus, SARS or MERS, as well as traditional medicine, herbal, remedy or plants, with 55 primary research articles identified. The overwhelming majority of publications focussed on polar compounds. Compounds that show promise for the inhibition of coronavirus in humans include scutellarein, silvestrol, tryptanthrin, saikosaponin B₂, quercetin, myricetin, caffeic acid, psoralidin, isobavachalcone, and lectins such as griffithsin. Other compounds such as lycorine may be suitable if a therapeutic level of antiviral activity can be achieved without exceeding toxic plasma concentrations. It was noted that the most promising small molecules identified as coronavirus inhibitors contained a conjugated fused ring structure with the majority being classified as being polyphenols.

Keywords: COVID-19; Coronaviridae; Middle East respiratory syndrome (MERS); SARS-CoV-2; Severe acute respiratory syndrome (SARS); Traditional medicine.

Graphical abstract

Fig. 1

The general structure of a coronavirus (reproduced from Wikipedia under CC licence 4.0). E protein = envelope protein.

Fig. 2

The structure of selected naturally occurring compounds that demonstrate promising anti-coronavirus activity. (1) Quercetin (2) Quercetin 7-rhamnoside (3) Myricetin (4) Psoralidin (5) Caffeic acid (6) Tryptanthrin (7) Lycorine (8) Scutellarein (9) Silvestrol (10) Saikosaponin B2 (11) Isobavachalcone (12) Griffithsin. As annotated on (4), note the aromatic rings and substituted fused rings present in most compounds.

Fig. 3

Possible binding sites of quercetin in SARS-CoV-2 3CLpro and tryptanthrin in PLpro. Docking was performed in AutoDock Vina 1.1.2 (Trott and Olson, 2010) against target proteins generated by SWISS-MODEL (https://swissmodel.expasy.org/repository/species/2697049).