. 2019 Sep 26;24(19):3486. doi: 10.3390/molecules24193486

Table 3.

Summary of anti-HIV compounds from marine organisms.

Group	Compound	Location	Organism	Assay	Dose	Activity	Structure	Reference
Peptide + chitosan oligomer	QMW-COS	not disclosed ^a	marine byproduct	IC₅₀—inhibition of HIV-1 induced lytic effects (cell viability assay) IC₅₀—inhibition of HIV-1_IIIB p24 antigen production (ELISA) IC₅₀—inhibition of HIV-1_RTMDR p24 antigen production (ELISA) IC₅₀—inhibition of virus-induced luciferase activity in infected TZM-bl cells IC₅₀—inhibition of the interaction between gp41 and CD4 (CD4-gp41 ELISA)	48.14 µg/mL 67.35 µg/mL 81.03 µg/mL 68.13 µg/mL 39.13 µg/mL	anti-HIV-1; inhibition of the HIV entry at an early stage, blocking the fusion of HIV-1 infected cells, interference of gp41-CD4 binding	+ glutamine (Q), methionine (M), tryptophan (W)	[31]
Peptide + chitosan oligomer	WMQ-COS	not disclosed^a	marine byproduct	IC₅₀—Inhibition of HIV-1 induced lytic effects (cell viability assay) IC₅₀—inhibition of HIV-1IIIB p24 antigen production (ELISA) IC₅₀—inhibition of HIV-1_RTMDR p24 antigen production (ELISA) IC₅₀—inhibition of virus-induced luciferase activity in infected TZM-bl cells IC₅₀—inhibition of interaction between gp41 and CD4 (CD4-gp41 ELISA)	48.01 µg/mL 98.73 µg/mL 144.02 µg/mL 250 µg/mL 51.48 µg/ml	anti-HIV-1; inhibition of the HIV entry at an early stage	+ tryptophan (W) methionine (M), glutamine (Q),	[31]
Sulfated polysaccharides	heparan sulfate (3)	not disclosed	-	EC₅₀—inhibition of HIV-1_IIIB strain (syncytia assay) EC₅₀—inhibition of HIV-1_IIIB strain (p24 assay) EC₅₀—inhibition of HIV-1_IIIB/H9 strain (co-cultivation assay) EC₅₀—inhibition of HIV-1_RF strain (p24 assay) EC₅₀—inhibition of HIV-1_KM018 strain (p24 assay) EC₅₀—inhibition of HIV-1_TC-2 strain (p24 assay) EC₅₀—inhibition of HIV-1_A17 strain (p24 assay) EC₅₀—inhibition of HIV-1_RF/V82F/184V strain (p24 assay) EC₅₀—inhibition of HIV-1_{L10R/M461/L63P/V82T/184V} strain (p24 assay) EC₅₀—inhibition of HIV-1_CBL-20 strain (syncytia assay) EC₅₀—inhibition of HIV-1_ROD strain (syncytia assay)	0.24 µg/mL 0.73 µg/mL 4.26 µg/mL 1.14 µg/mL 23.75 µg/mL 31.86 µg/mL 1.09 µg/mL 0.95 µg/mL 1.12 µg/mL 71.76 µg/mL97.63 µg/ml	anti-HIV-1; electrostatic interactions with basic amino acid residues of Tat		[53]
	fucose containing	Nha Trang bay, Vietnam	Sargassum mcclurei, Sargassum polycystum, and Turbinara Ornate brown seaweeds	U373-CD4-CXCR4 cells 211 infected with pseudotype viral IC₅₀—inhibition (F_SP crude extract)-(p24 ELISA) IC₅₀—inhibition (F_TO crude extract)-(p24 ELISA) IC₅₀—inhibition (F_SM crude extract)-(p24 ELISA)	0.34 µg/mL 0.39 µg/mL 0.96 µg/mL	anti-HIV-1; inhibition of the early phase of infection, by blocking the virus attachment and entry into the host cells		[56]
	ascophyllan (4)	not disclosed	different sources	IC₅₀—inhibition of HIV-1_R9-real-time PCR	1.3 µg/mL	anti-HIV-1; early step of HIV-1 (R9 and JR-Fl) infection; inhibition of VSV-G-pseudotyped HIV-1 infection in HeLa cells		[59]
	fucoidan S (5) fucoidan A (6)	not disclosed	different sources	IC₅₀—inhibition of HIV-1_R9-real-time PCR (fucoidan S) IC₅₀—inhibition of HIV-1_R9-real-time PCR (fucoidan A)	0.3 µg/mL 0.6 µg/ml	anti-HIV-1; early step of HIV-1 (R9 and JR-Fl) infection; inhibition of VSV-G-pseudotyped HIV-1 infection in HeLa cells		[59]
	chondroitin sulfate (7)	not disclosed		EC₅₀—HIV-1 p24 detection-PBMC assay-inhibition of HIV-1_IIIB, HIV-1_{L10R/M46I/L63P/V82T/I84V}, HIV-1_A17, HIV-1_RF, and HIV-1_RF/V82F/184V strains	0.01–0.08 μM	anti-HIV-1; inhibition of HIV-1 replication; inhibition of the HIV-1 entry		[61]
Lectins	KAA-1	not disclosed	red alga Kappaphycus alvarezii	IC₅₀—neutralization assay in Jurkat cells (median tissue culture infectious dose (TCID50) method using Jurkat cells)	9.2 nM	anti-HIV-1; inhibition of the HIV-1 entry		[87]
Lectins	KAA-2	not disclosed	red alga Kappaphycus alvarezii	IC₅₀—neutralization assay in Jurkat cells (median tissue culture infectious dose (TCID50) method using Jurkat cells)	7.3 nM	anti-HIV-1; inhibition of the HIV-1 entry		[87]
Peptides	stellettapeptin A (8)	north-western Australia	marine sponge Stelletta sp.	EC₅₀—inhibition of the cytotoxic effect upon HIV-1 infection	23 nm	anti-HIV-1; cytopathic effect of HIV-1 infection		[92]
Peptides	stellettapeptin B (9)	north-western Australia	marine sponge Stelletta sp.	EC₅₀—inhibition of the cytotoxic effect upon HIV-1 infection	27 nm	anti-HIV-1; cytopathic effect of HIV-1 infection		[92]
Bromotyrosine derivatives	aeroplysinin-1 (10)	Colombia	marine sponge Verongula rigida	% of inhibition of HIV-1 replication by flow cytometry % of reverse transcription inhibition (qPCR analysis of late transcripts) % of nuclear import inhibition (qPCR analysis of 2-LTR transcript) % of HIV entry inhibition (viral infectivity assay)	74% of inhibition at 20 µM 48% of inhibition at 10 µM 67% of inhibition at 10 µM dose dependent manner 2–20%	anti-HIV-1; inhibition of HIV-1 replication, RT, nuclear import and entry		[93]
	3,5-dibromo-N,N,N,O-tetramethyl Tyraminium (13)	Colombia	marine sponge Verongula rigida	% of HIV entry inhibition (viral infectivity assay)	dose depended manner 14–30%	anti-HIV-1; inhibition of HIV-1 entry		[93]
	19-deoxy fistularin 3 (15)	Colombia	marine sponge Verongula rigida	% of reverse transcription inhibition (qPCR analysis of early transcripts) % of reverse transcription inhibition (qPCR analysis of late transcripts) % of nuclear import inhibition (qPCR analysis of 2-LTR transcript)	35% inhibition at 20 µM 11% inhibition at 20 µM 62% inhibition at 20 µM	anti-HIV-1; inhibition of HIV-1 replication, RT, nuclear import		[93]
	purealidin B (16)	Colombia	marine sponge Verongula rigida	% of inhibition of HIV-1 replication by flow cytometry % of reverse transcription inhibition (qPCR analysis of early transcripts) % of reverse transcription inhibition (qPCR analysis of late transcripts) % of nuclear import inhibition (qPCR analysis of 2-LTR transcript) % of HIV entry inhibition (viral infectivity assay)	57% of inhibition at 80 µM58% of inhibition at 20 µM 34% of inhibition at 20 µM 66% of inhibition at 20 µM dose depended manner 2–11%	anti-HIV-1; inhibition of HIV-1 replication, RT, nuclear import and entry		[93]
	fistularin 3 (17)	Colombia	marine sponge Verongula rigida	% of reverse transcription inhibition (qPCR analysis of late transcripts) % of nuclear import inhibition (qPCR analysis of 2-LTR transcript) % of HIV entry inhibition (viral infectivity assay)	24% of inhibition at 5 µM, 47% of inhibition at 10 µM, dose depended manner 11–13%	anti-HIV-1; inhibition of, HIV-1 RT, nuclear import and HIV-1 entry		[93]
	3-bromo- 5-hydroxy-O-methyltyrosine (18)	Colombia	marine sponge Aiolochroia crassa	% of inhibition of HIV-1 replication by flow cytometry % of reverse transcription inhibition (qPCR analysis of early transcripts) % of reverse transcription inhibition (qPCR analysis of late transcripts) % of nuclear import inhibition (qPCR analysis of 2-LTR transcript) % of HIV entry inhibition (viral infectivity assay)	47% of inhibition at 80 µM, 54% of inhibition at 160 µM, 50% of inhibition at 40 µM, 73% of inhibition at 80 µM, dose depended manner 2–12%	anti-HIV-1; inhibition of HIV-1 replication, RT, nuclear import and entry		[93]
Peptides	APCHP (21)	not disclosed	Alaska pollack	EC₅₀—against anti-HIV-1 induced cell lysis (MTT assay) EC₅₀—HIV-1-induced RT activation in MT-4 cells EC₅₀—against p24 production (western blot)	459 µM (0.403 mg/mL) 374 µM (0.327 mg/mL) 405 µM (0.356 mg/mL)	anti-HIV-1; inhibition of induced syncytia formation by interference of HIV fusion inhibition of cell lysis, RT activity and production of p24 antigen		[94]
Peptides	SM-peptide	not disclosed	Spirulina maxima	IC₅₀—protective activity on HIV-1-induced cell lysis-MTT assay % of RT Inhibition in HIV-1-infected cells (reverse transcriptase assay kit) % of HIV-1 p24 antigen production (p24 antigen production assay)	0.691 mM (0.475 mg/mL) 90% inhibition at 1.093 mM (0.75 mg/mL) 95% of inhibition at 1.093 mM (0.75 mg/mL)	anti-HIV-1; inhibition of the HIV-1 RT activity and p24 antigen production	Leu-Asp-Ala-Val-Asn-Arg	[95]
Alkaloids	aspernigrin C (22)	Yongxing Island, South China Sea Yongxing Island, South China Sea	marine fungus Aspergillus niger SCSIO Jcw6F30 isolated from marine alga Sargassum sp.	IC₅₀—inhibitory effects on infection by CCR5-tropic HIV-1 SF162 in TZM-bl cells	4.7 μM	anti-HIV-1		[96]
	malformin C (23)	Yongxing Island, South China Sea Yongxing Island, South China Sea	marine fungus Aspergillus niger SCSIO Jcw6F30 isolated from marine alga Sargassum sp.	IC₅₀—inhibitory effects on infection by CCR5-tropic HIV-1 SF162 in TZM-bl cells	1.4 μM	anti-HIV-1		[96]
	eutypellazine E (24)	South Atlantic Ocean	deep-sea sediment fungus Eutypella sp. MCCC 3A00281	IC₅₀—anti-HIV bioassay-pNL4.3.Env-.Luc co-transfected 293T cells	3.2 μM	anti-HIV-1; inhibitory effects against HIV-1 replication		[97]
	eutypellazine J (25)	South Atlantic Ocean	deep-sea sediment fungus Eutypella sp. MCCC 3A00281	IC₅₀—anti-HIV bioassay-pNL4.3.Env-.Luc co-transfected 293T cells reactivation activity-In vitro latent HIV reactivating assay-flow cytometry-based screening	4.9 μM 80 μM	anti-HIV-1; inhibitory effects against HIV-1 replication, latency reactivating agent		[97]
	debromo- hymenialdisine (26)	Coral reefs in the Red Sea	S. carteri sponge extract	% of reduction of HIV-1 replication-cell-based assay	30% of inhibition at 13 μM	anti-HIV 1; decrease the transcription of the HIV-1, abrogate the G2-checkpoint of the cell cycle		[98]
	Hymenialdisine (27)	Coral reefs in the Red Sea	S. carteri sponge extract	% of reduction of HIV-1 replication-cell-based assay	<40% of inhibition at 3.1 µM	anti-HIV 1; decrease the transcription of the HIV-1, abrogate the G2-checkpoint of the cell cycle		[98]
	Oroidin (28)	Coral reefs in the Red Sea	S. carteri sponge extract	% of inhibition - HIV-1 RT biochemical assay % of reduction of HIV-1 replication-cell-based assay	90% of inhibition at >25 μM 50% of inhibition at 50 μM	anti-HIV-1; inhibition of HIV-1 RT, reduction of HIV-1 replication		[98]
	3-(phenetyl amino) demethyl(oxy) aaptamine (29)	Woody Island (Yongxing, Hainan, China) and Seven Connected Islets in the South China Sea	A. aptos sponge extract	% of inhibition against HIV-1 replication-anti-HIV-1 activity assay-cell-based VSVG/HIV-1 pseudotyping system	88% of inhibition at 10 μM	anti-HIV-1; inhibitory effects against HIV-1 replication		[99]
	3-(isopentyl amino) demethyl(oxy) aaptamine (30)	Woody Island (Yongxing, Hainan, China) and Seven Connected Islets in the South China Sea	A. aptos sponge extract	% of inhibition against HIV-1 replication-anti-HIV-1 activity assay-cell-based VSVG/HIV-1 pseudotyping system	72.3% of inhibition at 10 μM	anti-HIV-1; inhibitory effects against HIV-1 replication		[99]
	bengamide A (31)	not disclosed	screening of previously isolated compounds (originally isolated from the sponge Jaspis cf. coriacea)	EC₅₀—multi-cycle viral replication assay % inhibition of p24^Gag production-of PBMC assay-p24^Gag was quantified by ELISA EC₅₀—inhibition of LTR promoter-driven gene expression-LTR-based reporter assays	0.015 μM >90% of inhibition at 0.3 μM 0.17 μM	anti-HIV-1; inhibition of NF-κB-mediated retroviral gene expression		[100]
	haliclony- cyclamine A + B (32)	not disclosed	screening of previously isolated compounds	EC₅₀—multi-cycle viral replication assay	3.8 μM	anti-HIV-1; inhibitory effects against HIV-1 replication		[100]
	keramamine C (33)	not disclosed	screening of previously isolated compounds	EC₅—multi-cycle viral replication assay	3.4 μM	anti-HIV-1; inhibitory effects against HIV-1 replication		[100]
	stachybotrin D (34)	Xisha Island, China	sponge Xestospongia testudinaris	EC₅₀—inhibitory Effects on Wild-Type and NNRTI-Resistant HIV-1 Replication: EC₅₀—inhibition of VSVG/HIV-1_wt EC₅₀—inhibition of VSVG/HIV-1_RT-_K103N EC₅₀—inhibition of VSVG/HIV-1_RT_-_L100I,K103N EC₅₀—inhibition of VSVG/HIV-1_RT_-_K103N,V108I EC₅₀—inhibition of VSVG/HIV-1_RT_-_K103N,G190A EC₅₀—inhibition of VSVG/HIV-1_RT_-_K103N,_P225H	8.4 μM 7.0 μM 23.8 μM 13.3 μM 14.2 μM 6.2 μM	anti-HIV-1; HIV-1 RT inhibition (inhibitory effects on wild type and five NNRTI-resistant HIV-1 strains)		[101]
Diterpenes	dolabelladienol A (35)	Atol das Rocas, in Northeast Brazil	brown alga Dictyota pfaffii	EC₅₀—inhibition of the cytopathic effect of HIV-1-MT-2 cells—MTT method	2.9 μM	anti-HIV-1; - inhibition of the cytopathic effect of HIV-1		[102]
	dolabelladienol B (36)	Atol das Rocas, in Northeast Brazil	brown alga Dictyota pfaffii	EC₅₀—inhibition of the cytopathic effect of HIV-1-MT-2 cells—MTT method	4.1 μM	anti-HIV-1; - inhibition of the cytopathic effect of HIV-1		[102]
	dolastane (38)	Praia do Velho, Angra dos Reis, in the south of Rio de Janeiro State, Brazil	brown alga Canistrocarpus cervicornis	EC₅₀—inhibition of HIV-1 replication-CXCR4-tropic HIV-1–MTT method	0.35 μM	anti-HIV-1; inhibition of HIV-1 replication, potent effect on HIV-1 infectivity		[103]
	dolastane (39)	Praia do Velho, Angra dos Reis, in the south of Rio de Janeiro State, Brazil	brown alga Canistrocarpus cervicornis	EC₅₀—inhibition of HIV-1 replication-CXCR4-tropic HIV-1–MTT method	0.794 μM	anti-HIV-1; inhibition of HIV-1 replication, potent effect on HIV-1 infectivity		[103]
	secodolastane diterpene (40)	Praia do Velho, Angra dos Reis, in the south of Rio de Janeiro State, Brazil	brown alga Canistrocarpus cervicornis	EC₅₀—inhibition of HIV-1 replication-CXCR4-tropic HIV-1–MTT method	3.67 μM	anti-HIV-1; inhibition of HIV-1 replication		[103]
	8,10,18-trihydroxy-2,6-dolabelladiene (41)	Atol das Rocas reef, Brazil	brown alga Dictyota friabilis	EC₅₀—inhibition of the cytopathic effect of HIV-1-MT-2 cells—MTT method	6.16 μM	anti-HIV-1; inhibition of the cytopathic effect of HIV-1		[104,105]
	oxygenated dolabellane (42)	Santa Marta Bay (Colombian Caribbean Sea	octocoral Eunicea laciniata	EC₅₀—inhibition of HIV-1-Inhibition of the cytopathic effect of HIV-1-MT-2 cells—MTT method	3.9 μM	anti-HIV-1; inhibition of the cytopathic effect of HIV-1		[106]
	oxygenated dolabellane (43)	Santa Marta Bay (Colombian Caribbean Sea	octocoral Eunicea laciniata	EC₅₀—inhibition of the cytopathic effect of HIV-1-MT-2 cells—MTT method	0.73 μM	anti-HIV-1; inhibition of the cytopathic effect of HIV-1		[106]
	oxygenated dolabellane (44)	Santa Marta Bay (Colombian Caribbean Sea	octocoral Eunicea laciniata	EC₅₀—inhibition of HIV-1-Inhibition of the cytopathic effect of HIV-1-MT-2 cells–MTT method	0.69 μM	anti-HIV-1; inhibition of the cytopathic effect of HIV-1		[106]
	8,4′′′-dieckol (45)	not disclosed	brown alga, Ecklonia cava	Inhibition of syncytia formation on C8166 cells (HIV-1_IIIB, HIV-1_RF and HIV-1_LAI)-inverted microscope Inhibition of the cytopathic effect of HIV-1-C8166 cells—MTT method	Inhibition in dose-depended manner * Cell viability was more than 90% dose-dependent inhibition	anti-HIV-1; inhibition of the cytopathic effects of HIV-1: inhibition of syncytia formation, lytic effects, inhibition of viral p24 antigen production, HIV-1 entry inhibition and RT inhibition		[107]
				Effect on p24 antigen production-p24 antigen capture ELISA and immunoblast analysis RT activity assay—commercial fluorescence RT assay kit	Inhibited 91% activity of HIV-1_IIIB RT and approximat ely 80% for rest of the HIV-1 strains tested, HIV-1_RTMDR1 strain was inhibited at a ratio of 76.1%
				Inhibition of HIV-1 replication-Luciferase gene reporter assay	At the highest concentration, inhibition was more than 80% for all viral strains except for RTMDR1 (76.33%)
	penicilli- xanthone A (46)	not disclosed	from the jellyfish-derived fungus Aspergillus fumigates	IC₅₀—inhibition of PXA on infection by CCR5-tropic HIV-1 in TZM-bl cells IC₅₀—inhibition of PXA on infection by CXCR4-tropic HIV-1 in TZM-bl cells	0.36 μM 0.26 μM	anti-HIV-1; inhibition of infection against CCR5-tropic HIV-1 SF162 and CXCR4-tropic HIV-1 NL4-3		[108]
	docosahexanoic acid (48)	not disclosed		In vivo study on male rat models-Male F344 (control) and HIV-1Tg rats		anti-HIV-1; neuroprotective effect on neuroinflammations induced by ethanol (in the presence of HIV viral proteins)		[109]
Phlorotannins and xanthones	radicicol (49)	Tutuila, American Samoa	H. fuscoatra	EC₅₀—In Vitro Model of HIV-1 Latency-high-throughput primary cell-based HIV-1 latency assay	9.1 µM	anti-HIV-1; reactivation of latent viral loads in CD4+ T-cells		[110]
Phlorotannins and xanthones	pochonin B (50)	Tutuila, American Samoa	H. fuscoatra	EC₅₀—In Vitro Model of HIV-1 Latency-high-throughput primary cell-based HIV-1 latency assay	39.6 µM	anti-HIV-1; reactivation of latent viral loads in CD4+ T-cells		[110]
Auxiliary therapy to HAART therapy—fish oil	pochonin C (51)	Tutuila, American Samoa	H. fuscoatra	EC₅₀—In Vitro Model of HIV-1 Latency-high-throughput primary cell-based HIV-1 latency assay	6.3 µM	anti-HIV-1; reactivation of latent viral loads in CD4+ T-cells		[110]
Others	truncateol O (52)	Yongxing Island, Hainan Province of China	sponge-associated fungus Truncatella angustata	IC₅₀—Anti-HIV bioassays-VSV-G pseudotyped HIV-1–Luciferase assay system	39 µM	anti-HIV-1; inhibition of the HIV replication		[111]
Others	truncateol P (53)	Yongxing Island, Hainan Province of China	sponge-associated fungus Truncatella angustata	IC₅₀—Anti-HIV bioassays-VSV-G pseudotyped HIV-1–Luciferase assay system	16.1 µM	anti-HIV-1; inhibition of the HIV replication		[111]

^a Tripeptide conjugates of chitosan (a natural marine byproduct), prepared in the laboratory.