Natural Products with Inhibitory Activity against Human Immunodeficiency Virus Type 1

Table 1

Natural compounds with anti-HIV-1 activity extracted from fungi, plants, or marine sponges.

NC	Source/compound	Origin	Effect	IC50/EC50	CC50	SI/% inhibition ▪	Reference
Terpenes	Cipadessa cinerascens/; a. Ciparasin B	Leaves	Cytopathic effect	a. 5.5 μm/mL	ND	a. >7.2	[23]
	b. Ciparasin P			b. 6.1 μm/mL		b. >6.5
	Anisomeles indica/; Ovatodiolide			1.20 μm/mL/0.10 μm/mL	ND	80%–90% ▪	[24]
	Excoecaria acerifolia Didr./; Excocarinol A	Stem		>628.9 μM/5.58 μM	ND	>112.7	[25]
	Excoecaria acerifolia Didr./; a. Excoecafolin A			a. >473.93 μM/0.258 μM	ND	a. >1836.9	[26]
	b. Excoecafolin B			b. 15.52 μM/0.036 μM		b. 431.1
	c. Excoecafolin C			c. 13.74 μM/0.046 μM		c. 298.7
	d. Daphnopsis factor R2			d. >492.61 μM/0.978 μM		d. >503
	Trigonostemon lii/; a. Trigolin C			a. 2.04 μg/mL	a. 54.04	a. 26.49	[27]
	b. Trigolin G			b. 9.17 μg/mL	b. >200	b. >21.81
	c. Trigochinin A			c. 11.42 μg/mL	c. 106.45	c. 9.32
	d. Trigochinin F			d. 9.05 μg/mL	d. 86.54	b. 9.56
	Trigonostemon thyrsoideum/; a. Trigothysoid J	Twigs and leaves		a. 2.3 ± 1.20 nM	a. >251.2 nM	a. >101.2	[28]
	b. Trigothysoid L			b. 4.0 ± 0.11 nM	b. >296.7 nM	b. >74.0
	c. Trigothysoid N			c. 0.001 ± 0.76 × 10–3 nM	c. 22.2 ± 0.42 nM	c. 17.619
	d. Trigothysoid O			d. 0.358 ± 0.50 × 10–2 nM	d. 28.9 ± 5.91 nM	d. 80.8
	e. Rediocide A			e. 0.004 ± 0.11 × 10–2 nM	e. 22.9 ± 0.64 nM	e. 6077.3
	f. Rediocide C			f. 0.008 ± 0.98 × 10–3 nM	f. 27.9 ± 0.02 nM	f. 3245.9
	g. Rediocide F			g. 0.001 ± 0.60 × 10–3 nM	g. 15.2 ± 13.76 nM	g. 15.242
	h. Trigonosin F			h. 0.015 ± 0.85 × 10–3 nM	h. 23.8 ± 1.49 nM	b. 1618.8
	Syzygium claviflorum/; a. Betulinic acid	Leaves	Replication (quantification of p24 antigen)	a. 13 μM/1.4 μM	ND	a. 9.3	[29]
	b. Platanic acid			b. 90 μM/6.5 μM		b. 13
	c. Dihydrobetulinic acid			c. 13 μM/0.9 μM		c. 14
	Syzygium claviflorum/; 3-O-(3′,3′-dimethylsuccinyl) betulinic acid		Cytopathic effect	0.011 μg/mL	14.03 μg/mL	1.275	[30]
			Replication (quantification of p24 antigen)	10.3 nM (VIH WT) and 7.8 nM (drug-resistant HIV-1 isolates)	25 μM	>2.500	[31]
	Derived from betulinic acid	Commercial extract	Maturation	0.015 μM	>4.5 μM	ND	[32]
	3-O-(3′,3′- dimethylsuccinyl) betulinic acid + piperazine and caffeic acid
	Derived from betulinic acid RPR103611		Fusion	40 ± 19 nM	ND	>100	[33]
	Betulin-derived α-keto-GSK8999	Commercial extract	Protease	23 nM (HIV WT), 25 nM (HIV Q369H), 8 nM (HIV V370 A), and 17 nM (HIV T371 A)	ND	ND	[34]
	Geum japonicum/; Ursolic acid	Whole plant	Protease	ND	ND	85% at 17.9 μg/mL ▪	[35]
	P. glandulosa, P. juniperinum, S. claviflorum, H. capitata/; 3-0-Diglyoryl-ursolic acid	Leaves	Replication (quantification of p24 antigen)	48.2 μM/0.31 μM	ND	155.5	[36]
	Gardenia carinata/; a. Carinatin A	Leaves and twigs	Cytopathic effect	a. 27 μM/15.4 μM	ND	a. 1.8/6% ▪	[37]
	b. Carinatin B			b. 72.5 μM/62.7 μM		b. 1.2/1.9% ▪
	c. Carinatin E			c. 69.5 μM/43.0 μM		c. 1.6/63.7% ▪
	d. Carinatin F			d. >138.3 μM/41.3 μM		d. >3.4/11.6% ▪
	e. Carinatin G			e. 46 μM/13.4 μM		e. 3.4/25.5% ▪
	f. Dikamaliartane D			f. 57.7 μM/˂8.3 μM		f. >7/88.1% ▪
			RT	f. 68.7 μM
	Ganoderma lucidum/; a. Ganoderic acid α	Fruiting body	Protease	a. 0.19 mM	g. 15.6 μg/mL; h. 15.6 μg/mL; i. 15.6 μg/mL	ND	[38]
	b. Ganoderic acid B			b. 0.17 mM
	c. Ganoderic acid Cl			c. 0.18 mM
	d. Ganoderic acid H			d. 0.20 mM
	e. Ganoderiol A			e. 0.23 mM
	f. Ganoderiol B			f. 0.17 mM
	g. Ganoderiol F			g. 0.32 mM
	h. Ganodermanontriol			h. >1 mM
	i. 3β-5α-Dihydroxy-6β-methoxy ergosta-7,22-diene.			i. 0.18 mM
	Ganoderma lucidum/; a. Ganoderic acid ß			a. 20 μM	ND	ND	[39]
	b. Lucidumol B			b. 50 μM
	c. Ganodermanondiol			c. 90 μM
	d. Ganodermanontriol			d. 70 μM
	e. Ganolucidic acid A			e. 70 μM
	Gleditsia japónica/; Gleditsia saponin C	Fruits	Replication (quantification of p24 antigen)	9.8 μM/1.1 μM	ND	8.9	[40]
	Gymnocladus chinensis/; Gymnocladus saponin G			14 μM/2.7 μM	ND	5.2
Coumarins	Calophyllum lanigerum/; a. Calanolide A	Fruit and twigs	RT	a. 20 μM/0.1 μM	ND	a. 200	[41]
	b. Calanolide B			b. 15 μM/0.4 μM		b. 37
	Calophyllum brasiliense/; a. (+)-Calanolide A	Leaves	Replication (quantification of p24 antigen)	a. 0.34 μM/mL	ND	ND	[42]
	b. (-)-Calanolide B			b. 0.5 μM/mL
			RT	ND	ND	a. 81.5% ▪
						b. 76.2% ▪
	Calophyllum inophyllum Linn./	Leaves and twigs	RT	In a cell-free assay; a. 38 nM	a. 55 μM	a. 39 μM	[43]
	a. Inophyllum B			b. 130 nM	b. 25 μM
	b. Inophyllum P			In Molt-4 cells; a. 1.4 μM		b. 16 μM
				b. 1.6 μM
	C. cordato-oblongum Thw/; a. Cordatolide A	Leaves		Cell-free assay; a. 12.3 μM	ND	ND	[44]
				b. 19 μM
	b. Cordatolide B			In HOG.R5 cells; a. 19.3 μM	ND	a. 92 (200 μg/mL)	[45]
				b. 11.7 μM		b. 88 (200 μg/mL)
	Calophyllum brasiliense/; GUT-70	Stem bark	Replication (quantification of p24 antigen)	8.44 μM/3.48 μM (U1 cells (PMA))	ND	2.43 (U1 cells (PMA))	[46]
				8.44 μM/4.32 μM (U1 cells (TNF-α))		1.95 (U1 cells (TNF-α))
				>10 μM/3.41 μM (Molt-4 cells)		>2.93 (Molt-4 cells)
	Ferula sumbul/; Imperatorin	Root	Replication	>100 mg/mL/<0.10 mg/mL	ND	>1000	[47]
	Marila pluricostata/; a. Mesuol	Leaves and stem	Replication (luciferase activity)	a. 2 at 2.5 μM	ND	ND	[48]
	b. Isomesuol			b. 2 at 2.5 μM
Simple and related phenolic compounds	Humulus lupulus/; Xanthohumol	Hop	Cytopathic effect	0.82 μg/mL (2 μM)	8.82 μg/mL (21.51 μM)	10.8	[49]
			Replication (quantification of p24 antigen)	1.28 μg/mL (3.21 μM)
			RT	0.50 μg/mL (1.22 μM)
	Thalassia testudinum/; Thalassiolin A	Whole plant	Integrase	2.1 μM	ND	ND	[50]
			Strand transfer	0.4 μM
			Mg^+2-dependent strand transfer	2 μM
			Replication (MAGI assay)	30 μM
	Detarium microcarpum/; a. (−)-Epicatechin	Leaves	gp120	a. 2.0 μg/mL	a. >100 μg/mL	b. >100	[51]
	b. (−)-Epicatechin 3-O-gallate			b. 1.0 μg/mL	b. >100 μg/mL
	Camellia sinensis	Commercial extract	RT	1.6 μM	150 μM	ND	[52]
	Epigallocatechin (EGCG)
	Scutellariae radix/; Baicalin monohydrate	Root	Replication (quantification of p24 antigen)	0.5 μg/mL (PBMC infected with HIV-1)	ND	72% at 1 μg/mL (PBMC infected with HIV-1) ▪	[53]
				0.2 μg/mL (PBMC from HIV-1-infected individuals)		90% at 2 μg/mL (PBMC from HIV-1-infected individuals) ▪
			RT	2 μg/mL	ND	50% at 2 μg/mL ▪
	S. baicalensis Georgi/; Baicalin		Envelope	4 μM	ND	ND	[54]
	Myricetin	Commercial extract	Replication (quantification of p24 antigen)	- 20.43 μM (HIV-1 BaL in TZM-bl)	- 1214.72 μM (TZM-bl)	ND	[55]
				- 22.91 μM (HIV-1 MN in H9)	- 804.94 μM (HeLa)
				- 1.76 μM (HIV-1 89.6 in H9)	- 1159.26 μM (PBMC)
				- 4.49 μM (HIV-1 MN in PBMC)	- 1059.09 μM (H9)
				- 3.23 μM (HIV-1 89.6 in PBMC)
			RT	203.65 μM
	Dioscorea bulbifera/; Myricetin	Bulbils	Integrase	3.15 μM	ND	ND	[56]
	Marcetia taxifolia/; Myricetin	Aerial parts	Replication (quantification of p24 antigen)	230 μM	ND	ND	[57]
			RT	7.6 μM	ND	ND
	Curcuma longa/; Curcumin	Roots	Processing 3′	95 μM	ND	ND	[58]
			Strand transfer	40 μM	ND	ND
	a. L-chicoric acid	Synthetic	Processing 3′	a. 150 μM	ND	ND	[59]
				b. 6 ± 1.5 μM
	b. Dicaffeoylmethane			c. 9 ± 7 μM
			Strand transfer	a. 140 μM	ND	ND
	c. Rosmarinic acid			b. 3.1 ± 0.1 μM
				c. 4 ± 1.5 μM
	Curcuma longa/; a. Curcumin	Root	Replication (luciferase activity)	a. 0.7 μM (CEM-T cells)/12 μM (PBMC)	ND	ND	[60]
	b. Curcumin A			b. 0.8 μM (CEM-T cells) and 2 μM (PBMC)
	Curcuma longa/; L-chicoric acid	Synthetic	Integrase	500 nM at 10 μM	ND	ND	[61]
			Entry	1 μM
Proteins	Hericium coralloides/; H. coralloides laccase	Dried fruiting body	RT	0.06 μM	ND	ND	[62]
	Hericium erinaceum/; H. erinaceum laccase	Fresh fruiting body		9.5 μM	ND	ND	[63]
	Tricholoma mongolicum/; T. mongolicum laccase	Mycelium		0.65 μM	ND	ND	[64]
	Ganoderma lucidum/; G. lucidum laccase	Fresh fruiting body		1.2 μM	ND	ND	[65]
	Agaricus placomyces/; A. placomyces laccase	Fruiting body		1.25 μM	ND	ND	[66]
	Agrocybe cylindracea/; A. cylindracea laccase	Fresh fruiting body		12.7 μM	ND	ND	[67]
	Tricholoma giganteum/; T. giganteum laccase			2.2 μM	ND	ND	[68]
	Coprinus comatus/; C. comatus laccase	Mycelium		5.85 μM	ND	ND	[69]
	Pleurotus cornucopiae/; P. cornucopiae laccase	Fresh fruiting body		3.7 mM	ND	ND	[70]
				22 μM	ND	ND	[71]
	Clitocybe maxima/; C. maxima laccase			14.4 μM	ND	ND	[72]
	Lentinus tigrinus/; L. tigrinus laccase	Mycelium		2.4 μM	ND	ND	[73]
	Lentinus edodes/; L. edodes laccase	Fresh fruiting body		7.5 μM	ND	ND	[74]
	Agaricus bisporus/; A. bisporus lectin	Commercial lectin		1.9 μM	ND	ND	[75]
	Galanthus nivalis/; G. nivalis agglutinin	Bulbs	Cytopathic effect	0.4 μg/mL	ND	ND	[76]
	Hippeastrum hybrid/; H. hybrid agglutinin			0.4 μg/mL	ND	ND
	Narcissus pseudonarcissus/; N. pseudonarcissus agglutinin			0.6 μg/mL	ND	ND
	Listera ovata/; L. ovata agglutinin			0.3 μg/mL	ND	ND
	Epipactis helleborine/; E. helleborine agglutinin	Leaves		0.04 μg/mL	ND	ND	[77]
	Cymbidium hybrid/; C. hybrid agglutinin			0.08 μg/mL	ND	ND
	Myrianthus holstii/; M. holstii lectin	Root	Cytopathic effect	>50 μg/mL/1.4 μg/mL (150 nM)	ND	ND	[78]
	Oscillatoria agardhii/; O. agardhii agglutinin	Synthetic	Replication (quantification of p24 antigen)	24 ± 5 nM/0.51 μM	>7 μM (CEM-SS cells) and 0.51 μM (MT-4 cells)	ND	[79]
			Cytopathic effect	13 ± 3 nM
	Griffithsia/; Griffithsin	Aqueous extract	gp120	0.04 nM (HIV-1RF)-0.63 nM (HIV-1 T and M)	ND	ND	[80]
	Russula delica/; R. delica lectin	Fresh fruiting body	RT	0.26 μM	ND	- 23.8% at 0.08 μM ▪	[81]
						- 60.5% at 0.4 μM ▪
						- 94.2% at 2 μM ▪
	Pleurotus citrinopileatus/; P. citrinopileatus lectin			0.93 μM	ND	- 10% at 0.12 μM ▪	[82]
						- 43.7% at 0.6 μM ▪
						- 90.3% at 3 μM ▪
	Schizophyllum commune/; S. commune lectin			1.2 μM	ND	ND	[83]
	Pholiota adiposa/; P. adiposa lectin	Dried fruiting body		1.9 μM	ND	ND	[84]
	Inocybe umbrinella/; I. umbrinella lectin			4.7 ± 0.2 μM	ND	ND	[85]
	Boletus edulis/; B. edulis lectin	Fresh fruiting body		14.3 μM	ND	ND	[86]
	Hericium erinaceum/; H. erinaceum lectin	Dried fruiting body		31.7 μM	ND	ND	[87]
	Urtica dioica/; U. dioica agglutinin	Fruiting body	Cytopathic effect	0.9 μg/mL	ND	ND	[77]
	Flammulina velutipes/; a. Velutin	Fresh fruiting body	RT	a. ND	ND	ND	[88]
	b. Succinylated velutin			b. 5 μg/mL
	Lyophyllum shimeji/; a. Lyophyllin	Fruiting body		7.9 nM	ND	ND	[89]
	Hypsizygus marmoreus/; Hypsin			8 μM	ND	ND	[90]
	Hypsizygus marmoreus/; Marmorine			30 μM	ND	ND	[91]
	Luffa cylindrica/; Luffin P1	Seeds	Cytopathic effect	50 μM	235 μM	ND	[92]
			Replication (quantification of p24 antigen)	58 μM
	Momordica balsamina/; Balsamin			10.2 nM	∼8.75 μM	ND	[93]
	Phytolacca americana/; a. PAP-I	Leaves		a. 14 nM	ND	ND	[94]
	b. PAP-II			b. 26 nM
	c. PAP-III			c. 17 nM
Bromotyrosines	Psammaplysine D	Marine sponge	Replication	ND	ND	51% at 0.1 μg/mL ▪	[95]
	Aeroplysinin-1		Replication (reverse transcription assay)	3.76 μM/2.5 μM	ND	ND	[96]
			Replication (MAGI assay)	ND	ND	74% at 20 μM ▪	[97]
			Late transcripts	ND	ND	48% at 10 μM ▪
			Nuclear import	ND	ND	67% at 10 μM ▪
	Aiolochroia crassa/; Fistularine 3		Replication (reverse transcription assay)	10.3 μM/6.9 μM	ND	ND	[96]
	Verongula rigida/; Purealidin B		Replication (MAGI assay)	ND	ND	57% at 80 μM ▪	[97]
			Early transcripts	ND	ND	58% at 20 μM ▪
	Psammaplysilla purpurea/; Mololipids mixture		Replication (SAR study)	>100 μM/52.2 mM	ND	ND	[98]

NC: natural compound; EC₅₀: effective concentration 50%; IC₅₀: inhibitory concentration 50%; CC₅₀: cytotoxic concentration 50%; SI: selectivity index; RT: reverse transcriptase; ND: nondetermined; ▪: percentage inhibition.