Table 6 Potential alkaloid compounds acting as antiviral agents against SARS-CoV-2

Berbamine

Berberis

SARS-CoV-2

In vitro: in Vero cells

EC₅₀ =  ~ 2.3 mM

[293]

Emetin

Homoharringtonine (HHT)

Carapichea ipecacuanha and Cephalotoxus fortune

SARS-CoV-2 replication step

The virus, beta-CoV/Hongkong/VM20001061/2020, was isolated from the nasopharynx aspirate

In vitro: in Vero E6 cells

IC₅₀ of emetine and HHT were 0.46 mM and 2.55 mM, respectively

A combination of remdesivir at 6.25 mM with emetine at 0.195 mM resulted in 64.9% inhibition in viral yield

[294]

Berbamine (BE12)

Derivate of berbamine (BE33)

SARS-CoV-2 envelope protein containing ion permeable channels that regulates electrolyte balance, including potassium, sodium and calcium concentration in serum

In vitro: in Vero E6 cells and other 13 cell lines

In vivo: BE-33 was injected into mice, which significantly reduced cytokine secretion

IC₅₀ of BE12 and BE33 as: an inhibitor of envelope channels: 111.50 mM and 5.79 mM antivirus; 14.50 mM and 0.94 mM. Selection index of BE12 and BE33: 2.06 and 33.47

[295]

Isolated lycorine EC50 = 15.7 ± 1.2 nM; selective index (SI) > 900

Lycoris radiata (steam cortex)

Artemisia annua (whole plant)

Pyrrosia lingua (leaf)

Lindera aggregata (root)

SARS-CoV strain BJ001

In vitro: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay for virus-induced cytopathic effect (CPE)

L. radiata extract (EC₅₀ = 2.4 mg/mL; SI = 370)

A. annua extract (EC₅₀ = 34.5 mg/mL; SI = 31)

P. lingua extract (EC₅₀ = 43.2 mg/mL; SI = 55)

L. aggregata extract (EC₅₀ = 88.2 mg/mL; SI = 16)

[296]

Phycocyanobilins

Spirulina platensis and Spirulina maxima [297]

SARS-CoV-2 Mpro and PLpro

In vitro using FRET-based cleavage assay with SARS-CoV-2 Mpro and PLpro

IC₅₀ with Mpro and PLpro is 71 mM and 62 mM

[298]

Chloroquine

The bark of Cinchona tree

nCoV-2019BetaCoV/Wuhan/WIV04/2019

In vitro using qRT-PCR and immunofluorescence microscopy in Vero E6 cells

EC₅₀ = 1.13 μM; CC₅₀ > 100 μM, SI > 88.50

[299]

Berberine

Beta-sitosterol

Octacosanol

Tetrahydropalmatine

Choline

Tinospora cordifolia

3CLpro of SARS-CoV-2

In silico with ligand (6LU7)

Binding affinities in order: − 7.3; − 7.1; − 6.6; − 6.4; − 3.4 kcal/mol

Inhibition constant in order; 4.4 × mM; 6.16 × mM; 1.43 × mM; 2.01 × mM; 3.2 × mM

[300]

Schizanthine Z

Schizanthus porrigens

PLpro (6WX4) of SARS-CoV-2

In silico using Autodock Vina and PyRx with a ligand of 6WX4

Binding affinity: − 7.5 kcal/mol

[168]

Caffeine and nicotine

Active sites of the S protein in SARS-CoV-2

In silico using AutoDock v4.2 package with a ligand of 6LZG and 6VW1

Binding energy:

Nicotine + favipiravir + CTD-ACE2 = − 7.13 kcal/mass

Caffeine + ribavirin + RBD-ACE2 = − 6.76 kcal/mol

[301]

Thalimonine

Sophaline D

Tomatidine

Emetine

Mpro of SARS-CoV-2

In silico using AutoDock

Binding energy in order: − 8.39; − 8.79; − 9.58; − 10.17 kcal/mol

Inhibition constant in order: 0.706 mM; 0.36266 mM; 0.09544 mM;

0.03535 mM

[302]

Phycocyanobilins

SARS-CoV-2 Mpro (6LU7) and PLpro (6WUU)

In silico using AutoDock Vina

Binding energy of Mpro and PLpro is − 8.6 and − 9.8 kcal/mol

[298]

Bismahanine

Murraya koenigii (L.) Spreng (leaves)

SARS-CoV-2 spike protein (6M0J)

In silico using AutoDock Vina

Binding energy: − 9.1 kcal/mol

[164]

Quinine

The bark of Cinchona tree

SARS-CoV-2 Mpro (pdb id: 6m0k)

In silico using

Binding energy: − 6.2 kcal/mol

[303]