Table 7 Derivates of terpenes potentially act as antiviral agents

Black seed oil (BSO) or habatussaudah

Nigella sativa

Murine cytomegalo virus

In vivo using a viral plaque-forming assay of BALB/c mice spleen and liver

Undetected virus at the ratio of the effector to target cells was 20:1

[99]

Manuka oil

HSV

In vitro using a plaque reduction assay on RC-37 cells (monkey kidney cells)

IC₅₀ = 0.96 mg/mL

[318]

Laurus nobilis oil containing β-ocimene, 1,8-cineole, α-pinene, β-pinene

Laurus nobilis

SARS-CoV (isolate FFM-1 from Germany)

In vitro using visually scoring of the virus-induced cytopathogenic effect (CPE) for 48 h post-infection on Vero cells

IC₅₀:120 mg/mL; SI of 4.16

[101]

Ethyl acetate and methanol extracts of aerial parts of D. virgatus

Daucus virgatus (Poir.) Maire

Coxsackievirus B (CV-B)

In vitro using plaque reduction assay on Hep-2 cell line

IC₅₀ ethylacetate and methanol extracts = 98.16 and 60.08 mg/mL

[319]

Ethanol extracts

Mentha piperita

Desmodium canadense

Thymus vulgaris

Avian infectious bronchitis virus (IBV)

In vitro using plaque reduction assay on Vero cells

TCID = 1.83 ± 0.31–3.45 ± 0.21 log₁₀

EC₅₀ = 0.003–0.076 mg

[320]

Betulinic acid

SARS-CoV 3CL pro

In vitro using FRET method

IC₅₀ 10 mM

[95]

The fraction containing high of cannabidiol (F_CBD)

Cannabis sativa strain Arbel

Interleukin: IL-6 dan IL-8

In vitro using enzyme-link immunosorbent assay on A549 cells

IC₅₀ of 3.45 and 3.49 mg/mL

[311]

Artemisinin content

Artemisia annua L. (dried leaves)

SARS-CoV-2 USA/WA1

In vitro using cytophatic effect assay on Vero E6 cells infected by SARS-CoV-2

IC₅₀ of 0.01–0.14 mg

[313]

Cryptotanshinone

Salvia miltiorrhiza

SARS-CoV PLpro

In vitro using proteolysis of the fluorogenic substrate

IC₅₀ = 0.8 ± 0.2 μM

[321]

Dihydrotanshinone I

Salvia miltiorrhiza

SARS-CoV Mpro

In vitro using proteolysis of the fluorogenic substrate

IC₅₀ = 14.4 ± 0.7 μM

[321]

Pachymic acid

Dried sclerotia of Poria cocos (Schw.). Wolf

SARS-CoV-2 Mpro recombinant

In vitro using the fluorogenic substrate for inhibition assay

IC₅₀: 18.607 μM

[312]

Garlic essential oil containing 17 organosulfurs

ACE2 protein and main protease of SARS-CoV-2

In silico using MOE 2015.10 on ACE2 protein and 6LU7 (Mpro)

ACE2:

diallyl tetrasulfide and allyl disulfide − 14.06 and − 12.84 kcal/mol

Mpro:

Allyl disulfide and allyl trisulfide − 15.32 and − 15.02 kcal/mol

[322]

β-farnesene

α-farnesene

farnesol

α-bulnesene

SARS-CoV-2: Mpro (main protease), Nsp15/NendoU (endoribonucleoase), ADRP (ADP-ribose-1′′-phosphatase), rS (binding domain of the SARS-CoV-2 spike protein), RdRp (RNA-dependent RNA polymerase), and hACE2 (human angiotensin-converting enzyme)

In silico using Molegro Virtual Docker v. 6.0.1 on SARS-CoV-2 Mpro (5R7Z, 5R80, 5R81, 5R82, 5R83, 5R84, 6LU7, 6M03, 6Y84), Nsp15/NendoU (6VWW, 6W01, 6W02), rS (6M0J, 6M17, 6VX1, 6VW1), RdRp (6M71)

Docking Score (DS)

SARS-CoV-2 Mpro = (E)-β-farnesene − 115.4 kJ/mol

SARS-CoV Nsp15/NendoU = (E,E)-alpha-farnesene -107.5 kJ/mol

SARS-CoV-2 ADRP = (E)-β-farnesene -116.3 kJ/mol

SARS-CoV-2 RdRp = (E,E)-farnesol -89.6 kJ/mol

hACE2 = alpha-bulnesene < -100 kJ/mol

[207]

Eucalyptol (1,8-cineole) in eucalyptus oil

MPro/3CLpro of SARS-CoV-2

In silico using 1-click dock and swiss dock tools

DS = − 4.2

ΔG = − 6.04 kcal/mol

[323]

Jensenone in eucalyptus oil

MPro/3CLpro of SARS-CoV-2

In silico using 1-click dock and swiss dock tools

DS = − 5.5

ΔG = − 6.03 kcal/mol

[205]

Cuminal

Carvacrol

Myrtanol

Pinocarveol

Receptor binding domain (RBD) of the S1 glycoprotein (residues 319–541)

In silico using AutoDock Vina on RBD of SARS-CoV-2 S1 subunit (6M07)

Binding affinity (kcal/mol):

Cuminal − 4.9

Carvacrol − 4.9

Myrtanol − 5.3

Pinocarveol -5.0

[324]

Lauruside 5

Laurus nobilis

SARS-CoV-2

In silico using 1-Click Mcule on SARS-CoV-2 Mpro (6YB4)

Binding energy − 8.2 kcal/mol

[325]

Tanshinone I

SARS-CoV PLpro

In silico using Gold software with PLpro (6WX4)

IC₅₀ of 8.8 mM

[92]

3-β-O-(α-L-rhamnopyranosyl-(1- > 2)α-L-arabinopyranosyl)olean-12-ene-28-O-(α-L-rhamnopyranosyl-(1- > 4)-β-D-glucopyranosyl-(1- > 6)-β-D-glucopyranosyl)ester

SARS-CoV-2 S-RBD

In silico using Autodock Vina with ligand 6LZG

IC₅₀ of − 11 kcal/mol

[316]

Limonin and scopadulcic acid B

Dictamus dasycarpus, and Citrus orange

SARS-CoV-2 RdRp (6M71), hACE2 (6M1D), and Spike glycoprotein (2GHV)

In silico using Autodock 4.2

The docking score of limonin against RdRp, hACE2, and spike protein is − 9.0, − 8.9, and − 8.4. While docking score of scopadulcic acid B is − 8.6, − 8.2, and − 8.8

[192]

Carvacrol, anethol, cinnamyl acetate

SARS-CoV-2 RBD S1 subunit of S glycoprotein (6M0J)

In silico using AutoDock Vina

Binding affinities of three of them were − 5.2. kcal/mol

[326]

Coagulin N

Withania coagulans (Stocks) Dunal

SARS-CoV-2 spike protein (6M0J)

In silico using AutoDock Vina

Binding energy: − 9.1 kcal/mol

[164]

Glycyrrhizic acid

Glycyrrhiza glabra L. (liquorice roots)

SARS-CoV-2 TMPRSS2 (sequence NP_001128571.1)

In silico using AutoDock Vina

Binding energy: − 9.5 kcal/mol

[164]

Glycyrrhizin

Glycyrrhiza glabra L

SARS-CoV-2 spike RBD (6M0J)

In silico using AutoDock 4.2

Binding affinity: − 9.47 kcal/mol

[175]

Ashwagandhanolide, withacoagin, withaferin, and withanone

Ayurveda botanical: Withania somnifera (roots)

SARS-CoV-2 Mpro (5R84)

In silico using AutoDock 4.2.6

Docking score: − 9.9, and three other withanolide are − 8.8

[236]

Ashwagandhanolide, withacoagin, 27-hydroxywithanone

Ayurveda botanical: Withania somnifera (roots)

SARS-CoV-2 RBD spike glycoprotein (6M17)

In silico using AutoDock 4.2.6

Docking score: − 10, and two others are − 7.6

[236]

Ashwagandhanolide, muzanzagenin

Ayurveda botanical: Withania somnifera (roots)

SARS-CoV-2 RdRp (6M71)

In silico using AutoDock 4.2.6

Docking score: − 10.2 and − 9.3

[236]

Arjunic acid, theasapogenol B, euscaphic acid

Terminalia arjuna

Camelia sasanqua

Folium eriobortryde and Geum japonicum

SARS-CoV-2 Mpro (6LU7)

In silico using Autodock Vina

Binding affinities and inhibition constants:

− 8.1 kcal/mol and 1.16 μM − 8.1 kcal/mol and 1.16 μM

− 8.0 kcal/mol and 1.37 μM

[193]

Crocin, digitoxigenin, β-eudesmol,

Crocus sativus L

Nerium oleander

Lauris nobilis L

SARS-CoV-2 Mpro (6LU7)

In silico using Autodock 1.5.4

Binding energies: − 8.2, − 7.2, − 7.1 kcal/mol

[327]

Calendulaglycoside A

Calendula officinalis L

SARS-CoV-2 Mpro (6LU7)

In silico using MOE 2019 Suite

Binding-free energy: − 72.14 ± 38.78 kJ/mol

[174]