Plants and Natural Products with Activity against Various Types of Coronaviruses: A Review with Focus on SARS-CoV-2

Abstract

COVID-19 is a pandemic disease caused by the SARS-CoV-2 virus, which is potentially fatal for vulnerable individuals. Disease management represents a challenge for many countries, given the shortage of medicines and hospital resources. The objective of this work was to review the medicinal plants, foods and natural products showing scientific evidence for host protection against various types of coronaviruses, with a focus on SARS-CoV-2. Natural products that mitigate the symptoms caused by various coronaviruses are also presented. Particular attention was placed on natural products that stabilize the Renin-Angiotensin-Aldosterone System (RAAS), which has been associated with the entry of the SARS-CoV-2 into human cells.

Keywords: angiotensin-converting enzyme inhibitors (ACEi); antiviral; biomolecules; coronavirus disease of 2019 (COVID-19); medicinal plants; middle east respiratory syndrome (MERS); renin–angiotensin–aldosterone system (RAAS); severe acute respiratory syndrome coronavirus (SARS-CoV); viral entry inhibitors.

Figure 1

Various active principles and their mechanism of action. The infection cycle of SARS-CoV-2 in human cells. The SARS-CoV-2 spike (S) protein binds to ACE2 in host cells followed by priming of protein S by transmembrane protease serine 2 protease (TMPRSS2). Then, the virus produces the polyproteins pp1a and pp1ab, which are processed by viral proteases (3CLpro/Mpro, PLpro) to non-structural proteins (nsps), including RNA-dependent RNA polymerase (RdRp). Viral RdRp synthesizes a full-length complementary negative-strand RNA as a template for the production of the positive strand genome of the virus. Subgenomic mRNAs are then translated into structural proteins in the rough endoplasmic reticulum or in the cytosol. The viral genomic RNA is encapsulated by the nucleocapsid protein N and, finally, the virus is released by exocytosis. The blunt arrows indicate the possible targets of the active principles of medicinal plants. Irreversibly interference with viral docking receptors: Caphtharic acid (o), cichoric acid and echinacoside from Echinacea purpurea (p), vitamins D, C and Zn (q). Entry locks: Emodin (a), lectins (b), quercetin (c), catechin (d), naringenin (e), hesperetin (f), baicalin (g), epigallocatechin (h), gallocatechin gallate (i), prodelphinidin (af), gallocatechin (ag), saikosaponins derivatives of oleanane from Heteromorpha arborescens and Bupleurum spp. (aj), glycyrrhizine (al), Licorice (am), desmethoxyreserpine (ao), dihydrotanshinone I (ay). ACE2 receptor blocking: Emodin (a), hesperetin (f), kaempferol (j), anthocyanins (t), phenolic compounds: tannic acid (aa), 3-isotheaflavin-3-gallate (ab) and theaflavin-3,3′-digallate (ac) from Camellia sinensis. TMPRSS2 receptor blocking: [6]-gingerol (ak). Block the entry of cells through endocytosis: Butanol extract (v) and procyanidins (ai) from Cinnamomum verum. Inhibit 3CLpro: Quercetin (c), kaempferol (j), curcumin (y), sinigrin (z), eugenol (an), betulinic acid (ap), coumaroyltyramine (aq), cryptotanshinone (ar), desmethoxyreserpine (ao), Dihomo-γ-linolenic acid (au), lignan (as), sugiol (at), N-cis-feruloyltyramine (av), Tanshinone IIa (aw). Inhibit PLpro: Quercetin (c), baicalin (g), kaempferol (j), myricetin (n), scutellarein (l), eugenol (an), coumaroyltyramine (aq), cryptotanshinone (ar), N-cis-feruloyltyramine (av), Tanshinone IIa (aw), moupinamide (ax). Affinity with S protein: Eugenol (an), dihydrotanshinone I (ay). Viral replication: Aescin (k), kaempferol (j), resveratrol (s), prodelphinidin (af), gallocatechin (ag), epigallocatechin isomer (ah) from Pelargonium sidoides, essential oils: β-ocimene, 1,8-cineole, α-pinene and β-pinene (ad), phenolic compounds: tannic acid (aa), 3-isotheaflavin-3-gallate (ab) and theaflavin-3,3′-digallate (ac), betulinic acid (ap), desmethoxyreserpine (ao), lignan (as), sugiol (at). Affects the release or assembly of the virus: Phenolic compounds: tannic acid (aa), 3-isotheaflavin-3-galalate (ab) and theaflavin-3,3′-digallate (ac), lectin agglutinin (w) from Hippeastrum striatum. TNF-β, IL-1β expressions: Quercetin (c), luteoloside (m), chlorogenic acid (x) geranylated flavonoids (tomebrin A, B, D and E) (r), resveratrol (s), anthocyanins (t), gallic acid (u), prodelphinidin (af), gallocatechin (ag), epigallocatechin isomer (ah).

Figure 2

Mechanism of action of SARS-CoV-2 on the Renin–Angiotensin–Aldosterone System (RAAS) and its possible regulation by the Angiotensin converting enzyme inhibitors (ACEi), Angiotensin receptor blockers ARBs or Angiotensin converting enzyme (ACE2) that converts AI to A1-7 to restore the RAAS.