Microbial Natural Products with Anti-Human Immunodeficiency Virus: Comparison
Please note this is a comparison between Version 4 by Amina Yu and Version 3 by Amina Yu.

The resurgence and re-emergence of fatal viral infections pose a grave threat to public health. The emergence and spread of animal viruses are existential threats to humanity due to a number of intertwined and synergistic events, such as altered human behaviors, high-density rapid urbanization and demographic shift, modernization that encourages people with high mobility, large gatherings, global warming and destruction that altered the ecosystem, and an inadequate global public health system. Human immunodeficiency virus (HIV) is a type of retrovirus that infects humans. 

  • Microbial Natural Products
  • HIV
  • Human Immunodeficiency Virus

1. Brief Introduction to Anti-Human Immunodeficiency Virus

The primary transmission mode of HIV is genital-to-genital contact, blood, sperm, and blood transfusion. This virus attacks the body’s immune system, leading to acquired immunodeficiency syndrome (AIDS), a condition in which the immune system gradually fails, allowing dangerous opportunistic infections and cancer to develop. HIV primarily infects cluster of differentiation 4+ (CD4+) T cells, dendritic cells, and macrophages [1].
Furthermore, the condition may reduce the number of CD4+ T cells to a critical level, resulting in a loss of cell-mediated immunity and greater susceptibility to opportunistic infection, eventually leading to AIDS [2]. As of 2019, the World Health Organization (WHO) estimates that 38 billion people worldwide are infected with HIV [3]. However, approximately 1.7 million people were unaware they were HIV-positive [3]. Therefore, several antiretroviral drugs that may slow the progression of HIV in the body have been discovered and developed. Antiretroviral drugs were only recently available to 67% of the world’s population. Lopinavir, darunavir, atazanavir, and saquinavir are protease inhibitors, while lamivudine, stavudine, emtricitabine, efavirenz, nevirapine, and rand aziridine are reverse transcription inhibitors [4]. However, no HIV drug on the market can cure HIV.

2. Microbial Natural Products with Anti-Human Immunodeficiency Virus

Natural products produced by microorganisms, as shown in Table 1, could be used to develop anti-HIV medications. Anti-HIV bioactive compounds from fungi are widely considered to be one of the most promising sources. Several compounds, including alachalasin A from Podospora vesticola fungus cultures, have been identified as effective HIV-1 replication suppressors in cellosaurus cells C8166 [5][6]. The half-maximal effective concentration, or EC50, of alachalasin is 8.01 μM. Pestalofone A, as well as its derivatives, including pestalofone B and E, as well as pestaloficiol G, H, J, and K isolated from the Pestalotiopsis fici fungus, possess anti-HIV activity [7][8]. Furthermore, epicoccin G and H were isolated from ascomycete Epicoccum nigrum fermentation culture, in addition to its diphenylalazine A [9]. Another study discovered that bacillamide B, derived from the ascomycete Tricladium sp., exhibited anti-HIV activity [10]. Furthermore, cytochalasan alkaloids, such as armochaetoglobin K, L, M, N, O, P, Q, and R, purified from the arthropod-associated Chaetomium globosum fungus had significant anti-HIV activity (EC50 = 0.25–0.55 μM) [11].
Table 1. Natural product produce by microbes and its target.
Compound Name [Ref.] Compound Type Microbial Strain Strain Origin/Host Viral Target IC50/EC50/ED50 Target Inhibition
alachalasin A [5] alkaloid Podospora vesticola XJ03-56-1 glacier HIV-1 EC50 = 8.01 μM ND
pestalofone A [8] terpenoid Pestalotiopsis fici W106-1 plant endophyte HIV-1 EC50 = 90.4 μM ND
pestalofone B [8] terpenoid P. fici W106-1 plant endophyte HIV-1 EC50 = 64.0 μM ND
pestalofone E [8] terpenoid P. fici W106-2 plant endophyte HIV-1 EC50 = 93.7 μM ND
pestaloficiol G [8] terpenoid P. fici W106-3 plant endophyte HIV-1 EC50 = 89.2 μM ND
pestaloficiol H [8] terpenoid P. fici W106-4 plant endophyte HIV-1 EC50 = 89.2 μM ND
pestaloficiol J [8] terpenoid P. fici W106-5 plant endophyte HIV-1 EC50 = 8 μM ND
pestaloficiol K [8] terpenoid P. fici W106-6 plant endophyte HIV-1 EC50 = 78.2 μM ND
epicoccin G [12] alkaloid Epicoccum nigrum XZC04-CS-302 Cordyceps sinensis fungus HIV-1 EC50 = 13.5 μM ND
epicoccin H [12] alkaloid E. nigrum XZC04-CS-302 C. sinensis HIV-1 EC50 = 42.2 μM ND
diphenylalazine A [12] peptide E. nigrum XZC04-CS-302 C. sinensis HIV-1 EC50 = 27.9 μM ND
bacillamide B [10] peptide Tricladium sp. No. 2520 soil in which C. sinensis grow HIV-1 EC50 = 24.8 μM ND
armochaetoglobin K [11] alkaloid Chaetomium globosum TW 1-1 Armadillidium vulgare insect HIV-1 EC50 = 1.23 μM ND
armochaetoglobin L [11] alkaloid C. globosum TW 1-1 A. vulgare insect HIV-1 EC50 = 0.48 μM ND
armochaetoglobin M [11] alkaloid C. globosum TW 1-1 A. vulgare insect HIV-1 EC50 = 0.55μM ND
armochaetoglobin N [11] alkaloid C. globosum TW 1-1 A. vulgare insect HIV-1 EC50 = 0.25 μM ND
armochaetoglobin O [11] alkaloid C. globosum TW 1-1 A. vulgare insect HIV-1 EC50 = 0.61 μM ND
armochaetoglobin P [11] alkaloid C. globosum TW 1-1 A. vulgare insect HIV-1 EC50 = 0.68 μM ND
armochaetoglobin Q [11] alkaloid C. globosum TW 1-1 A. vulgare insect HIV-1 EC50 = 0.31 μM ND
armochaetoglobin R [11] alkaloid C. globosum TW 1-1 A. vulgare insect HIV-1 EC50 = 0.34 μM ND
stachybotrin D [13] terpenoid Stachybotrys chartarum MXH-X73 Xestospongia testudinaris sponge HIV-1 EC50 = 8.4 μM replication
stachybotrysam A [14] alkaloid S. chartarum CGMCC 3.5365. ND HIV-1 EC50 = 9.3 μM ND
stachybotrysam B [14] alkaloid S. chartarum CGMCC 3.5365. ND HIV-1 EC50 = 1.0 μM ND
stachybotrysam C [14] alkaloid S. chartarum CGMCC 3.5365. ND HIV-1 EC50 = 9.6 μM ND
chartarutine B [15] alkaloid S. chartarum WGC-25C-6 Niphates sp. sponge HIV-1 IC50 = 4.90 μM ND
chartarutine G [15] alkaloid S. chartarum WGC-25C-6 Niphates sp. sponge HIV-1 IC50 = 5.57 μM ND
chartarutine H [15] alkaloid S. chartarum WGC-25C-6 Niphates sp. sponge HIV-1 IC50 = 5.58 μM ND
malformin C [16] peptide Aspergillus niger SCSIO Jcsw6F30 marine HIV-1 IC50 = 1.4 μM entry
aspernigrin C [17] alkaloid A. niger SCSIO Jcsw6F30 marine HIV-1 IC50 = 4.7 μM entry
eutypellazine E [18] alkaloid Eutypella sp. MCCC 3A00281 deep sea sediment HIV-1 IC50 = 3.2 μM ND
truncateol O [19] terpenoid Truncatella angustata XSB-01-43 Amphimedon sp. sponge HIV-1 and H1N1 IC50 = 39.0 μM (HIV) and 30.4 μM (H1N1) ND
truncateol P [19] terpenoid T. angustata XSB-01-43 Amphimedon sp. sponge HIV-1 IC50 = 16.1 μM ND
penicillixanthone A [20] polyketide Aspergillus fumigatus jellyfish HIV-1 IC50 = 0.26 μM entry
DTM [21] polyketide C. globosum deep sea sediment HIV-1 75.1% at 20 μg/mL ND
epicoccone B [21] polyketide C. globosum deep sea sediment HIV-1 88.4% at 20 μg/mL ND
xylariol [21] polyketide C. globosum deep sea sediment HIV-1 70.2% at 20 μg/mL ND
phomonaphthalenone A [22] polyketide Phomopsis sp. HCCB04730 Stephania japonica-plant endophyte HIV-1 IC50: 11.6 μg/mL ND
bostrycoidin [22] polyketide Phomopsis sp. HCCB04730 S. japonica plant endophyte HIV-1 IC50: 9.4 μg/mL ND
altertoxin I [23] phenalene Alternaria tenuissima QUE1Se Quercus emoryi plant endophyte HIV-1 IC50: 1.42 μM ND
altertoxin II [23] phenalene A. tenuissima QUE1Se Q. emoryi plant endophyte HIV-1 IC50: 0.21 μM ND
altertoxin III [23] phenalene A. tenuissima QUE1Se Q. emoryi plant endophyte HIV-1 IC50: 0.29 μM ND
alternariol 5-O-methyl ether [24] phenolic Colletotrichum sp plant endophyte HIV-1 EC50: 30.9 μM replication
ergokonin A [25] terpenoid Trichoderma sp. Xy24 Xylocarpus granatum plant endophyte HIV-1 IC50: 22.3 μM ND
ergokonin B [25] terpenoid Trichoderma sp. Xy24 X. granatum plant endophyte HIV-1 IC50: 1.9 μM ND
sorrentanone [25] terpenoid Trichoderma sp. Xy24 X. granatum plant endophyte HIV-1 IC50: 4.7 μM ND
cerevisterol [25] terpenoid Trichoderma sp. Xy24 X. granatum plant endophyte HIV-1 IC50: 9.3 μM ND
phomopsone B [26] alkaloid Phomopsis sp. CGMCC 5416 Achyranthes bidentata plant endophyte HIV-1 IC50: 7.6 μmol/L ND
phomopsone C [26] alkaloid Phomopsis sp. CGMCC 5416 A. bidentata plant endophyte HIV-1 IC50: 0.5 μmol/L ND
pericochlorosin B [27] polyketide Periconia sp. F-31 plant endophyte HIV-1 IC50: 2.2 μM ND
asperphenalenone A [28] alkaloid Aspergillus sp. Kadsura longipedunculata plant endophyte HIV-1 IC50: 4.5 μM ND
asperphenalenone D [28] alkaloid Aspergillus sp. K. longipedunculata plant endophyte HIV-1 IC50: 2.4 μM ND
cytochalasin Z8 [28] alkaloid Aspergillus sp. K. longipedunculata plant endophyte HIV-1 IC50: 9.2 μM ND
epicocconigrone A [28] alkaloid Aspergillus sp. K. longipedunculata plant endophyte HIV-1 IC50: 6.6 μM ND
neoechinulin B/NeoB [29][30][31] alkaloid Aspergillus amstelodami ND HCV and SARS-CoV-2 IC50: 5.5 μM (HCV) and 32.9 μM (SARS-CoV-2) replication
Eurotium rubrum F33 marine sediment H1N1 IC50; 7 μM entry
raistrickindole A [32] alkaloid Penicillium raistrickii IMB17-034 mangrove sediment HCV EC50: 5.7 μM ND
raistrickin [32] alkaloid P. raistrickii IMB17-035 mangrove sediment HCV EC50: 7.0 μM ND
sclerotigenin [32] alkaloid P. raistrickii IMB17-036 mangrove sediment HCV EC50: 5.8 μM ND
harzianoic acid A [25] terpenoid Trichoderma harzianum LZDX-32-08 Xestospongia testudinaria sponge HCV IC50: 5.5 μM entry
harzianoic acid B [25] terpenoid T. harzianum LZDX-32-08 X. testudinaria sponge HCV IC50: 42.9 μM entry
peniciherquamide C [33] peptide Penicillium herquei P14190 seaweed HCV IC50: 5.1 μM ND
cyclo (L-Tyr-L-Pro) [34] peptide Aspergillus versicolor Spongia officinalis sponge HCV IC50: 8.2 μg/mL replication
7-dehydroxyl-zinniol [35] alkaloid Alternia solani Aconitum transsectum plant endophyte HBV IC50: 0.38 mM ND
THA [36] polyketide Penicillium sp. OUCMDZ-4736 mangrove sediment HBV IC50: 4.63 μM ND
MDMX [36] polyketide Penicillium sp. OUCMDZ-4736 mangrove sediment HBV IC50: 11.35 μM ND
vanitaracin A [37] polyketide Talaromyces sp. sand HBV IC50: 10.58 μM entry
destruxin A [38] peptide Metarhizium anisopliae var. dcjhyium Odontoternes formosanus termite HBV IC50: 1.2 μg/mL (mix A+B+E) ND
destruxin B [38] peptide M. anisopliae var. dcjhyium; O. formosanus termite HBV IC50: 1.2 μg/mL (mix A+B+E) ND
destruxin E [38] peptide M. anisopliae var. dcjhyium O. formosanus termite HBV IC50: 1.2 μg/mL (mix A+B+E) ND
amphiepicoccin A [12] alkaloid Epicoccum nigrum HDN17-88 Amphilophus sp. fish gill HSV-2 IC50: 70 μM ND
amphiepicoccin C [12] alkaloid E. nigrum HDN17-88 Amphilophus sp. fish gill HSV-2 IC50: 64 μM ND
amphiepicoccin F [12] alkaloid E. nigrum HDN17-88 Amphilophus sp. fish gill HSV-2 IC50: 29 μM ND
aspergillipeptide D [39] peptide Aspergillus sp. SCSIO 41501 gorgonian coral HSV-1 IC50: 7.93 μM entry
aspergilol H [40] polyketide Aspergillus versicolor SCSIO 41501 deep sea sediment HSV-1 EC50 = 4.68 μM ND
aspergilol I [40] polyketide A. versicolor SCSIO 41503 deep sea sediment HSV-1 IC50 = 6.25 μM ND
coccoquinone A [40] polyketide A. versicolor SCSIO 41504 deep sea sediment HSV-1 IC50 = 3.12 μM ND
trichobotrysin A [41] alkaloid Trichobotrys effuse DFFSCS021 deep sea sediment HSV-1 IC50 = 3.08 μM ND
trichobotrysin B [41] alkaloid Trichobotrys effuse DFFSCS021 deep sea sediment HSV-1 IC50 = 9.37 μM ND
trichobotrysin D [41] alkaloid Trichobotrys effuse DFFSCS021 deep sea sediment HSV-1 IC50 = 3.12 μM ND
11a-dehydroxyisoterreulactone A [42] terpenoid Aspergillus terreus SCSGAF0162 gorgonian corals Echinogorgia aurantiaca HSV-1 IC50 = 16.4 μg/mL ND
arisugacin A [42] terpenoid Aspergillus terreus SCSGAF0162 gorgonian corals E. aurantiaca HSV-1 IC50 = 6.34 μg/mL ND
isobutyrolactone II [42] terpenoid Aspergillus terreus SCSGAF0162 gorgonian corals E. aurantiaca HSV-1 IC50 = 21.8 μg/mL ND
aspernolide A [42] terpenoid Aspergillus terreus SCSGAF0162 gorgonian corals E. aurantiaca HSV-1 IC50 = 28.9 μg/mL ND
halovir A [43] peptide Scytalidium sp. NI HSV-1 and HSV-2 ED50 = 1.1 μM (HSV-1) and 0.28 (HSV-2) ND
halovir B [43] peptide Scytalidium sp. NI HSV-1 ED50 = 3.5 μM ND
halovir C [43] peptide Scytalidium sp. NI HSV-1 ED50 = 2.2 μM ND
halovir D [43] peptide Scytalidium sp. NI HSV-1 ED50 = 2.0 μM ND
halovir E [43] peptide Scytalidium sp. NI HSV-1 ED50 = 3.1 μM ND
balticolid [44] polyketide Ascomycetous fungus driftwood HSV-1 IC50 = 0.45 μM ND
alternariol [45] phenolic Pleospora tarda Ephedra aphylla endphyte HSV-1 IC50 = 13.5 μM ND
alternariol-(9)-methyl ether [45] phenolic Pleospora tarda E. aphylla endophyte HSV-1 IC50 = 21.3 μM ND
oblongolide Z [46] polyketide Phomopsis sp. BCC 9789 Musa acuminata endophyte HSV-1 IC50: 14 μM ND
DHI [47] phenolic Torrubiella tenuis BCC 12732 Homoptera scale insect HSV-1 IC50: 50 μg/mL ND
cordyol C [48] polyketide Cordyceps sp. BCC 1861 Homoptera-cicada nymph HSV-1 IC50: 1.3 μg/mL ND
DTD [49] polyketide Streptomyces hygroscopicus 17997 GdmP mutant HSV-1 IC50: 0.252 μgmol/L ND
labyrinthopeptin A1/LabyA1 [50] peptide Actinomadura namibiensis DSM 6313 desert soil HSV-1 and HSV-2 EC50 = 0.56 μM (HSV-1) and 0.32 μM (HSV-2) entry
HIV-1 and HIV-2 EC50 = 2.0 μM (HIV-1) and 1.9 μM (HIV-2) entry
monogalactopyranose [51] polyphenol Acremonium sp. BCC 14080 palm leaf HSV IC50: 7.2 μM ND
mellisol [52] polyketide Xylaria mellisii BCC 1005 NI HSV IC50: 10.5 μg/mL ND
DOG [52] polyketide Xylaria mellisii BCC 1005 NI HSV IC50: 8.4 μg/mL ND
spirostaphylotrichin X [53] polyketide Cochliobolus lunatus SCSIO41401 marine algae H1N1 and H3N2 IC50: 1.6 μM (H1N1) and 4.1 μM (H3N2) replication
cladosin C [54] polyketide Cladosporium sphaerospermum 2005-01-E3 deep sea sludge H1N1 IC50: 276 μM ND
abyssomicin Y [50] polyketide Verrucosispora sp. MS100137 deep sea sediment H1N1 inhibition rate: 97.9% ND
purpurquinone B [55] polyketide Penicillium purpurogenum JS03-21 acidic red soil H1N1 IC50: 61.3 μM ND
purpurquinone C [55] polyketide Penicillium purpurogenum JS03-22 acidic red soil H1N1 IC50: 64 μM ND
purpurester A [55] polyketide Penicillium purpurogenum JS03-23 acidic red soil H1N1 IC50: 85.3 μM ND
TAN-931 [55] polyketide Penicillium purpurogenum JS03-24 acidic red soil H1N1 IC50: 58.6 μM ND
pestalotiopsone B [56] polyketide Diaporthe sp. SCSIO 41011 Rhizophora stylosa mangrove endophte H1N1 and H3N2 IC50: 2.56 μM (H1N1) and 6.76 μM (H3N2) ND
pestalotiopsone F [56] polyketide Diaporthe sp. SCSIO 41012 R. stylosa mangrove endophte H1N1 and H3N2 IC50: 21.8 μM (H1N1) and 6.17 μM (H3N2) ND
DMXC [56] polyketide Diaporthe sp. SCSIO 41013 R. stylosa mangrove endophte H1N1 and H3N2 IC50: 9.4 μM (H1N1) and 5.12 μM (H3N2) ND
5-chloroisorotiorin [56] polyketide Diaporthe sp. SCSIO 41014 R. stylosa mangrove endophte H1N1 and H3N2 IC50: 2.53 μM (H1N1) and 10.1 μM (H3N2) ND
3-deoxo-4b-deoxypaxilline [57] alkaloid Penicillium camemberti mangrove sediment H1N1 IC50: 28.3 μM ND
DCA [57] alkaloid P. camemberti OUCMDZ-1492 mangrove sediment H1N1 IC50: 38.9 μM ND
DPT [57] alkaloid P. camemberti OUCMDZ-1492 mangrove sediment H1N1 IC50: 32.2 μM ND
9,10-diisopentenylpaxilline alkaloid P. camemberti OUCMDZ-1492 mangrove sediment H1N1 IC50: 73.3 μM ND
TTD [57] alkaloid P. camemberti OUCMDZ-1492 mangrove sediment H1N1 IC50: 34.1 μM ND
emindole SB [57] alkaloid P. camemberti OUCMDZ-1492 mangrove sediment H1N1 IC50: 26.2 μM ND
21-isopentenylpaxilline [57] alkaloid P. camemberti OUCMDZ-1492 mangrove sediment H1N1 IC50: 6.6 μM ND
paspaline [57] alkaloid P. camemberti OUCMDZ-1492 mangrove sediment H1N1 IC50: 77.9 μM ND
paxilline [57] alkaloid P. camemberti OUCMDZ-1492 mangrove sediment H1N1 IC50: 17.7 μM ND
(14S)-oxoglyantrypine [58] alkaloid Cladosporium sp. PJX-41 mangrove sediment H1N1 IC50: 85 μM ND
norquinadoline A [58] alkaloid Cladosporium sp. PJX-42 mangrove sediment H1N1 IC50: 82 μM ND
deoxynortryptoquivaline [58] alkaloid Cladosporium sp. PJX-43 mangrove sediment H1N1 IC50: 85 μM ND
deoxytryptoquivaline [58] alkaloid Cladosporium sp. PJX-44 mangrove sediment H1N1 IC50: 85 μM ND
tryptoquivaline [58] alkaloid Cladosporium sp. PJX-45 mangrove sediment H1N1 IC50: 89 μM ND
quinadoline B [58] alkaloid Cladosporium sp. PJX-46 mangrove sediment H1N1 IC50: 82 μM ND
22-O-(N-Me-l-valyl)-21-epi-aflaquinolone B [59] alkaloid Aspergillus sp strain XS-2009 Muricella abnormaliz gorgonian RSV IC50: 0.042 μM ND
aflaquinolone D [59] alkaloid Aspergillus sp strain XS-2009 M. abnormaliz gorgonian RSV IC50: 6.6 μM ND
aurasperone A [60] polyphenol Aspergillus niger No.LC582533 Phallusia nigra tunicate SARS-CoV-2 IC50: 12.25 μM replication
neoechinulin A [30] alkaloid Aspergillus fumigatus MR2012 marine sediment SARS-CoV-2 IC50: 0.47 μM replication
aspulvinone D [61] polyphenol Cladosporium sp. 7951 Paris polyphylla endophyte SARS-CoV-2 IC50: 10.3 μM replication
aspulvinone M [61] polyphenol Cladosporium sp. 7951 P. polyphylla endophyte SARS-CoV-2 IC50: 9.4 μM replication
aspulvinone R [61] polyphenol Cladosporium sp. 7952 P. polyphylla endophyte SARS-CoV-2 IC50: 7.7 μM replication
Abbreviations: * ND: not yet described, * NI; no information, * DTM: 1,3-dihydro-4,5,6-trihydroxy-7-methylisobenzofuran, * THA: 1,2,4,5-tetrahydroxy-7-((2R)-2-hydroxypropyl) anthracene-9,10-dione, * MDMX: methyl 6,8-dihydroxy-3-methyl-9-oxo-9H-xanthene-1-carboxylate, * DHI: 6,8-dihydroxy-3-hydroxymethyl isocoumarin, * DOG: 1,8-dihydroxynaphthol 1-O-glucopyranoside, * DMXC: 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate, * TTD: (6S,7R,10E,14E)-16-(1H-indol-3-yl)-2,6,10,14-tetramethylhexadeca-2,10,14-triene-6,7-diol, * DTD: 4,5-dihydro-thiazinogeldanamycin, * DCA: 4a-demethylpaspaline-4a-carboxylic acid, * DPT: 4a-demethylpaspaline-3,4,4a-triol.
An ocean-dwelling fungus is one of the most potent sources of HIV-combating compounds. Meroterpenoids with a phenylspirodrimane skeleton, such as stachybotrin D, derived from the sponge-derived fungus Stachybotrys chartarum MXH-X73, were able to inhibit HIV-1 replication by targeting the reverse transcriptase enzyme [13]. This fungus was discovered on the island of Xisha in China, where it was isolated from the marine sponge Xestospongia testudinaris [13]. Furthermore, stachybotrysams A, B, and C, extracted from a different strain of Stachybotrys chartarum, also showed strong HIV-inhibitory activity [14]. Another report showed that chartarutine B, G, and H, which are all derived from the sponge-associated Stachybotrys chartarum, have shown significant antiviral activity against the HIV-1 virus [15]. In addition, malformin C, derived from the marine fungus Aspergillus niger SCSIO Jcsw6F30, demonstrated significant anti-HIV-1 activity with an IC50, a half-maximal inhibitory concentration, of 1.4 μM when tested on HIV-infected TZM-bl cells (also called JC.53bl-13) [16]. In addition, aspernigrin C from the same fungus also demonstrated similar action with an IC50 of 4.7 μM [16].
An anti-HIV bioassay conducted in 293T cells, also refered as a highly transfectable derivative of human embryonic kidney 293 cells, revealed that eutypellazine E, extracted from a fungus found in the depths of the ocean named Eutypella sp., significantly inhibited HIV-1 proliferation [18]. Furthermore, unlike truncateol P, truncateol O, which is derived from the ascomycete Truncatella angustata, was found to inhibit the replication of both the H1N1 and HIV-1 viruses [19]. In addition, penicillixanthone A which is derived from the fungus Aspergillus fumigatus that is native to jellyfish, has been shown to possess significant anti-HIV-1 activity by inhibiting the infection of CXCR4-tropic HIV-1 NL4-3 and CCR5-tropic HIV-1 SF162 [20]. Additionally, the fungus Chaetomium globosum found in the depths of the ocean was able to produce 1,3-dihydro-4,5,6-trihydroxy-7-methylisobenzofuran, epicoccone B, and xylariol [21]. They showed highly effective anti-HIV activity in vitro at the concentration of 20 μg/mL, with 75.10, 88.4, and 70.20% suppression rates, respectively [21].
Endophytic fungus metabolites have been demonstrated to possess a vast array of bioactivities, including anti-HIV properties. Phomonaphthalenone A and bostrycoidin, both of which were derived from the endophytic fungus Phomopsis sp., showed moderate anti-HIV activity and low cytotoxicity, with IC50 values of 11.6 and 9.4 μg/mL, respectively [22]. In addition, altertoxin I, II and III derived from the endophytic fungus Alternaria tenuissima QUE1Se inhibited HIV-1 virus replication completely [23]. The epoxyperylene structure of these molecules is a promising scaffold for the development of potent and non-toxic anti-HIV therapies [23]. Alternariol 5-O-methyl ether, on the other hand, was identified as a molecule that inhibits HIV-1 pre-integration processes after screening a library of bioactive compounds from the endophytic fungus Colletotrichum sp. [24]. Ergokonin A and B isolated from the endophytic fungus Trichoderma sp. Xy24 had IC50 values of 1.9 μM, which indicated that it significantly suppressed the HIV-1 virus [25]. Recently, it was discovered that the endophytic fungus Phomopsis sp. CGMCC No. 5416 produces phomopsone B and C, and these two phomopsones have significant antiviral activity, with IC50 values of 7.6 and 0.5 μmol/L, respectively [26]. Furthermore, the phenol pericochlorosin B, isolated from the endophytic fungus Periconia sp. F-31, showed significant anti-HIV activity in 293T cells, with an IC50 value of 2.2 μM [27]. In 2017, Pang et al. discovered four compounds produced by the plant endophytic fungus Aspergillus sp. That belong to phenalenone derivatives [28]. These compounds include asperphenalenone A and D, cytochalasin Z8, and epicocconigrone A, which have anti-HIV activities in vitro with IC50 values of 4.5, 2.4, 9.2, and 6.6 μM, respectively [28]. The endophytic fungus was isolated from the Kadsura longipedunculata plant, also known as the Chinese Kadsura Vine, and used in traditional Chinese medicine [28]. Lamivudine and efavirenz, two control positives, demonstrated a greater activity level, with IC50 values of 0.1 and 0.0004 μM, respectively [28].

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