Abstract
Viruses have always been a class of pathogenic microorganisms that threaten the health and safety of human life worldwide. However, for a long time, the treatment of viral infections has been slow to develop, and only a few antiviral drugs have been using clinically. Compared with these from terrestrial environments, marine-derived microorganisms can produce active substances with more novel structures and unique functions. From 2015 to 2019, 89 antiviral compounds of 8 structural classes have been isolated from marine microorganisms, of which 35 exhibit anti-H1N1 activity. This review surveys systematically marine microbial-derived natural products with antiviral activity and illustrates the impact of these compounds on antiviral drug discovery research.
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Avilala J, Kumar AP, Viswanath B, Gopal DVRS, Narasimha G (2018) Antiviral and larvicidal properties of novel bioactive compounds produced from marine actinomycetes. Russ J Mar Biol 44:424–428. https://doi.org/10.1134/S106307401805005X
Barlow A, Landolf KM, Barlow B, Yeung SYA, Heavner JJ, Claassen CW, Heavner MS (2020) Review of emerging pharmacotherapy for the treatment of coronavirus disease 2019. Pharmacotherapy 40:416–437. https://doi.org/10.1002/phar.2398
Bhadury P, Mohammad BT, Wright PC (2006) The current status of natural products from marine fungi and their potential as anti-infective agents. J Ind Microbiol Biotechnol 33:325–337. https://doi.org/10.1007/s10295-005-0070-3
Cao X, Shi Y, Wu X, Wang K, Huang S, Sun H, Dickschat JS, Wu B (2019) Talaromyolides A–D and talaromytin: polycyclic meroterpenoids from the fungus Talaromyces sp. CX11. Org Lett 21:6539–6542. https://doi.org/10.1021/acs.orglett.9b02466
Che Q, Qiao L, Han X, Liu Y, Wang W, Gu Q, Zhu T, Li D (2018) Anthranosides A–C, anthranilate derivatives from a sponge-derived Streptomyces sp. CMN-62. Org Lett 20:5466–5469. https://doi.org/10.1021/acs.orglett.8b02382
Chen X, Si L, Liu D, Proksch P, Zhang L, Zhou D, Lin W (2015) Neoechinulin B and its analogues as potential entry inhibitors of influenza viruses, targeting viral hemagglutinin. Eur J Med Chem 93:182–195. https://doi.org/10.1016/j.ejmech.2015.02.006
Deshmukh SK, Prakash V, Ranjan N (2017) Marine fungi: a source of potential anticancer compounds. Front Microbiol 8:2536. https://doi.org/10.3389/fmicb.2017.02536
Dolezal M, Zitko J (2012) Pyrazine derivatives: a patent review. Expert Opin Ther Pat 22:1033–1051. https://doi.org/10.1517/13543776.2014.982533
Goh VS, Mok CK, Chu JJ (2020) Antiviral natural products for arbovirus infections. Molecules 25:2796. https://doi.org/10.3390/molecules25122796
Henning H-G, Gelbin A (1993) Advances in tetramic acid chemistry. Adv Heterocycl Chem 57:139–185. https://doi.org/10.1016/S0065-2725(08)60888-0
Hermawan I, Higa M, Hutabarat PUB, Fujiwara T, Akiyama K, Kanamoto A, Haruyama T, Kobayashi N, Higashi M, Suda S, Tanaka J (2019) Kabirimine, a new cyclic imine from an okinawan dinoflagellate. Mar Drugs 17:353–361. https://doi.org/10.3390/md17060353
Hou L, Wang S, Huang H, Li H, Wang W, Li W (2018) Generation of methylated violapyrones with improved anti-influenza A virus activity by heterologous expression of a type III PKS gene in a marine Streptomyces strain. Bioorg Med Chem Lett 28:2865–2868. https://doi.org/10.1016/j.bmcl.2018.07.029
Hou XM, Wang CY, Gerwick WH, Shao CL (2019) Marine natural products as potential anti-tubercular agents. Eur J Med Chem 165:273–292. https://doi.org/10.1016/j.ejmech.2019.01.026
Huang Z, Nong X, Ren Z, Wang J, Zhang X, Qi S (2017) Anti-HSV-1, antioxidant and antifouling phenolic compounds from the deep-sea-derived fungus Aspergillus versicolor SCSIO 41502. Bioorg Med Chem Lett 27:787–791. https://doi.org/10.1016/j.bmcl.2017.01.032
Huang H, Song Y, Li X, Wang X, Ling C, Qin X, Zhou Z, Li Q, Wei X, Ju J (2018) Abyssomicin monomers and dimers from the marine-derived Streptomyces koyangensis SCSIO 5802. J Nat Prod 81:1892–1898. https://doi.org/10.1021/acs.jnatprod.8b00448
Huang H, Song Y, Zang R, Wang X, Ju J (2019) Octyl substituted butenolides from marine- derived Streptomyces koyangensis. Nat Prod Res 5:1–6. https://doi.org/10.1080/14786419.2019.1686368
Jia Y-L, Guan F-F, Ma J, Wang C-Y, Shao C-L (2015) Pestalotiolide A, a new antiviral phthalide derivative from a soft coral-derived fungus Pestalotiopsis sp. Nat Prod Sci 21:227–230. https://doi.org/10.20307/nps.2015.21.4.227
Jia Y-L, Wei M-Y, Chen H-Y, Guan F-F, Wang C-Y, Shao C-L (2015) (+)- and (–)-Pestaloxazine A, a pair of antiviral enantiomeric alkaloid dimers with a symmetric spiro[oxazinane-piperazinedione]skeleton from Pestalotiopsis sp. Org Lett 17:4216–4219. https://doi.org/10.1021/acs.orglett.5b01995
Jin Y, Qin S, Gao H, Zhu G, Wang W, Zhu W, Wang Y (2017) An anti-HBV anthraquinone from aciduric fungus Penicillium sp. OUCMDZ-4736 under low pH stress. Extremophiles 22:39–45. https://doi.org/10.1007/s00792-017-0975-6
Kang H-H, Zhang H-B, Zhong M-J, Ma L-Y, Liu D-S, Liu W-Z, Ren H (2018) Potential antiviral Xanthones from a coastal saline soil fungus Aspergillus iizukae. Mar Drugs 16:449–457. https://doi.org/10.3390/md16110449
Kelecom A (2002) Secondary metabolites from marine microorganisms. An Acad Bras Cienc 74:151–170. https://doi.org/10.1590/S0001-37652002000100012
Khan MT, Ali A, Wang Q, Irfan M, Khan A, Zeb MT, Zhang YJ, Chinnasamy S, Wei DQ (2020) Marine natural compounds as potents inhibitors against the main protease of SARS-CoV-2-a molecular dynamic study. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2020.1769733
Kong F-D, Ma Q-Y, Huang S-Z, Wang P, Wang J-F, Zhou L-M, Yuan J-Z, Dai H-F, Zhao Y-X (2017) Chrodrimanins K–N and related meroterpenoids from the fungus Penicillium sp. SCS-KFD09 isolated from a marine worm, Sipunculus nudus. J Nat Prod 80:1039–1047. https://doi.org/10.1021/acs.jnatprod.6b01061
Leon B, Navarro G, Dickey BJ, Stepan G, Tsai A, Jones GS, Morales ME, Barnes T, Ahmadyar S, Tsiang M, Geleziunas R, Cihlar T, Pagratis N, Tian Y, Yu H, Linington RG (2015) Abyssomicin 2 reactivates latent HIV-1 by a PKC- and HDAC- independent mechanism. Org Lett 17:262–265. https://doi.org/10.1021/ol503349y
Li G, Kusari S, Spiteller M (2014) Natural products containing ′decalin′ motif in microorganisms. Nat Prod Rep 31:1175–1201. https://doi.org/10.1039/c4np00031e
Li J, Hu Y, Hao X, Tan J, Li F, Qiao X, Chen S, Xiao C, Chen M, Peng Z, Gan M (2019) Raistrickindole A, an anti-HCV oxazinoindole alkaloid from Penicillium raistrickii IMB17-034. J Nat Prod 82:1391–1395. https://doi.org/10.1021/acs.jnatprod.9b00259
Li J, Wang Y, Hao X, Li S, Jia J, Guan Y, Peng Z, Bi H, Xiao C, Cen S, Gan M (2019) Broad-spectrum antiviral natural products from the marine-derived Penicillium sp. IMB17-046. Molecules 24:2821–2831. https://doi.org/10.3390/molecules24152821
Li H, Liu SM, Yu XH, Tang SL, Tang CK (2020) Coronavirus disease 2019 (COVID 19): current status and future perspectives. Int J Antimicrob Agents 55:105951–105959. https://doi.org/10.1016/j.ijantimicag.2020.105951
Liao H-X, Sun D-W, Zheng C-J, Wang C-Y (2017) A new hexahydrobenzopyran derivative from the gorgonian-derived Fungus Eutypella sp. Nat Prod Res 31:1640–1646. https://doi.org/10.1080/14786419.2017.1285301
Liu F-A, Lin X, Zhou X, Chen M, Huang X, Yang B, Tao H (2017) Xanthones and quinolones derivatives produced by the deep-sea-derived fungus Penicillium sp. SCSIO Ind16F01. Molecules 22:1999–2005. https://doi.org/10.3390/molecules22121999
Liu H, Chen Z, Zhu G, Wang L, Du Y, Wang Y, Zhu W (2017) Phenolic polyketides from the marine alga-derived Streptomyces sp. OUCMDZ-3434. Tetrahedron 73:5451–5455. https://doi.org/10.1016/j.tet.2017.07.052
Lou Z, Sun Y, Rao Z (2014) Current progress in antiviral strategies. Trends Pharmacol Sci 35:86–102. https://doi.org/10.1016/j.tips.2013.11.006
Ma X, Nong X-H, Ren Z, Wang J, Liang X, Wang L, Qi S-H (2017) Antiviral peptides from marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501. Tetrahedron Lett 58:1151–1155. https://doi.org/10.1016/j.tetlet.2017.02.005
Manimaran M, Rajkumar T, Vimal S, Taju G, Majeed SA, Hameed AS, Kannabiran K (2018) Antiviral activity of 9 (10H)-Acridanone extracted from marine Streptomyces fradiae strain VITMK2 in Litopenaeus vannamei infected with white spot syndrome virus. Aquaculture 488:66–73. https://doi.org/10.1016/j.aquaculture.2018.01.032
Minagawa K, Kouzuki S, Yoshimoto J, Kawamura Y, Tani H, Iwata T, Terui Y, Nakai H, Yagi S, Hattori N, Fujiwara T, Kamigauchi T (2002) Stachyflin and acetylstachyflin, novel anti-influenza A virus substances, produced by Stachybotrys sp. RF-7260. I. Isolation, structure elucidation and biological activities. J Antibiot 55:155–164. https://doi.org/10.1002/chin.200233246
Minagawa K, Kouzuki S, Kamigauchi T (2002) Stachyflin and acetylstachyflin, novel anti-influenza A virus substances, produced by Stachybotrys sp. RF-7260. II. Synthesis and preliminary structure-activity relationships of stachyflin derivatives. J Antibiot 55:165–171. https://doi.org/10.1002/chin.200233246
Miniyar PB, Murumkar PR, Patil PS, Barmade MA, Bothara KG (2013) Unequivocal role of pyrazine ring in medicinally important compounds: a review. Mini Rev Med Chem 13:1607–1625. https://doi.org/10.2174/1389557511313110007
Moghadamtousi SZ, Nikzad S, Kadir HA, Abubakar S, Zandi K (2015) Potential antiviral agents from marine fungi: an overview. Mar Drugs 13:4520–4538. https://doi.org/10.3390/md13074520
Niu S, Si L, Liu D, Zhou A, Zhang Z, Shao Z, Wang S, Zhang L, Zhou D, Lin W (2016) Spiromastilactones: a new class of influenza virus inhibitors from deep-sea fungus. Eur J Med Chem 108:229–244. https://doi.org/10.1016/j.ejmech.2015.09.037
Niu S, Liu D, Shao Z, Proksch P, Lin W (2017) Eutypellazines A–M, thiodiketopiperazine-type alkaloids from deep sea derived fungus Eutypella sp. MCCC 3A00281. RSC Adv 7:33580–33590. https://doi.org/10.1039/C7RA05774A
Numata A, Takahashi C, Matsushita T, Miyamoto T, Kawai K, Usami Y, Matsumura E, Inoue M, Ohishi H, Shingua T (1992) Fumiquinazolines, novel metabolites of a fungus isolated from a saltfish. Tetrahedron Lett 33:1621–1624. https://doi.org/10.1016/S0040-4039(00)91690-3
Pang X, Lin X, Wang J, Liang R, Tian Y, Salendra L, Luo X, Zhou X, Yang B, Tu Z, Liu Y (2018) Three new highly oxygenated sterols and one new dihydroisocoumarin from the marine sponge-derived fungus Cladosporium sp. SCSIO41007. Steroids 129:41–46. https://doi.org/10.1016/j.steroids.2017.12.001
Pech-Puch D, Berastegui-Cabrera J, Pérez-Povedano M, Villegas-Hernández H, Guillén-Hernández S, Cautain B, Reyes F, Pachón J, Gómez P, Rodríguez J, Jiménez C, Sánchez-Céspedes J (2020) Antiviral and antiproliferative potential of marine organisms from the Yucatan Peninsula. Front Mar Sci, Mexico. https://doi.org/10.3389/fmars.2020.00607
Qin C, Lin X, Lu X, Wan J, Zhou X, Liao S, Tu Z, Xu S, Liu Y (2014) Sesquiterpenoids and xanthones derivatives produced by sponge-derived fungus Stachybotry sp. HH1 ZSDS1F1-2. J Antibiot 68:121–125. https://doi.org/10.1038/ja.2014.97
Rowley DC, Kelly S, Kauffman CA, Jensen PR, Fenical W (2003) Halovirs A–E, new antiviral agents from a marine-Derived fungus of the genus Scytalidium. Bioorg Med Chem 11:4263–4274. https://doi.org/10.1016/S0968-0896(03)00395-X
Saleem M, Nazir M, Ali MS, Hussain H, Lee YS, Riaz N, Jabbar A (2010) Antimicrobial natural products: an update on future antibiotic drug candidates. Nat Prod Rep 27:238–254. https://doi.org/10.1039/b916096e
Schobert R, Schlenk A (2008) Tetramic and tetronic acids: an update on new derivatives and biological aspects. Bioorg Med Chem 16:4203–4221. https://doi.org/10.1016/j.bmc.2008.02.069
Seghal Kiran G, Ramasamy P, Sekar S, Ramu M, Hassan S, Ninawe AS, Selvin J (2018) Synthetic biology approaches: towards sustainable exploitation of marine bioactive molecules. Int J Biol Macromol 112:1278–1288. https://doi.org/10.1016/j.ijbiomac.2018.01.149
Sun Y-L, Wang J, Wang Y-F, Zhang X-Y, Nong X-H, Chen M-Y, Xu X-Y, Qi S-H (2015) Cytotoxic and antiviral tetramic acid derivatives from the deep-sea-derived fungus Trichobotrys effuse DFFSCS021. Tetrahedron 71:9328–9332. https://doi.org/10.1002/chin.201611226
Tian Y-Q, Lin X-P, Wang Z, Zhou X-F, Qin X-C, Kaliyaperumal K, Zhang T-Y, Tu Z-C, Liu Y (2015) Asteltoxins with antiviral activities from the marine sponge-derived fungus Aspergillus sp. SCSIO XWS02F40. Molecules 21:34–43. https://doi.org/10.3390/molecules21010034
Vijayaraj R, Altaff K, Rosita AS, Ramadevi S, Revathy J (2020) Bioactive compounds from marine resources against novel corona virus (2019-nCoV): in silico study for corona viral drug. Nat Prod Res. https://doi.org/10.1080/14786419.2020.1791115
Wang J-F, Liang R, Liao S-R, Yang B, Tu Z-C, Lin X-P, Wang B-G, Liu Y (2017) Vaccinols J–S, ten new salicyloid derivatives from the marine mangrove-derived endophytic fungus Pestalotiopsis vaccinii. Fitoterapia 120:164–170. https://doi.org/10.1016/j.fitote.2017.06.013
Yang S-Q, Li X-M, Li X, Li H-L, Meng L-H, Wang B-G (2018) New citrinin analogues produced by coculture of the marine algal-derived endophytic fungal strains Aspergillus sydowii EN-534 and Penicillium citrinum EN-535. Phytochem Lett 25:191–195. https://doi.org/10.1016/j.phytol.2018.04.023
Yasuhara-Bell J, Lu Y (2010) Marine compounds and their antiviral activities. Antiviral Res 86:231–240. https://doi.org/10.1016/j.antiviral.2010.03.009
Yu G, Zhou G, Zhu M, Wang W, Zhu T, Gu Q, Li D (2015) Neosartoryadins A and B, fumiquinazoline alkaloids from a mangrove-derived fungus Neosartorya udagawae HDN13-313. Org Lett 18:244–247. https://doi.org/10.1021/acs.orglett.5b02964
Yu M-L, Guan F-F, Cao F, Jia Y-L, Wang C-Y (2017) A new antiviral pregnane from a gorgonian-derived Cladosporium sp. fungus. Nat Prod Res 32:1260–1266. https://doi.org/10.1080/14786419.2017.1342086
Zhang P, Li Y, Jia C, Lang J, Niaz S-I, Li J, Yuan J, Yu J, Chen S, Liu L (2017) Antiviral and anti-inflammatory meroterpenoids: stachybonoids A–F from the crinoid-derived fungus Stachybotrys chartarum 952. RSC Adv 7:49910–49916
Zhao X-Q (2011) Genome-based studies of marine microorganisms to maximize the diversity of natural products discovery for medical treatments. Evid Based Complement Alternat Med 2011:384572–384584. https://doi.org/10.1007/978-1-4614-6418-1_759-1
Zhao Y, Si L, Liu D, Proksch P, Zhou D, Lin W (2015) Truncateols A–N, new isoprenylated cyclohexanols from the sponge-associated fungus Truncatella angustata with anti-H1N1 virus activities. Tetrahedron 71:2708–2718. https://doi.org/10.1016/j.tet.2015.03.033
Zhao Y, Liu D, Proksch P, Zhou D, Lin W (2018) Truncateols O-V, further isoprenylated cyclohexanols from the sponge-associated fungus Truncatella angustata with antiviral activities. Phytochemistry 155:61–68. https://doi.org/10.1016/j.phytochem.2018.07.017
Acknowledgements
This Paper is Dedicated to Professor Youyou Tu, the 2015 Nobel Prize Laureate of Physiology or Medicine on the Occasion of Her 90th Birthday. This work was supported by the Program of National Natural Science Foundation of China (Grant Nos. U1706210, 41906090, and 41776141), the Program of Natural Science Foundation of Shandong Province of China (Grant No. ZR2019BD047), the Fundamental Research Funds for the Central Universities (No. 201841004), the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology (Qingdao) (Grant No. 2018SDKJ0403-2), the Taishan Scholars Program, China (Grant No. tsqn20161010).
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Teng, YF., Xu, L., Wei, MY. et al. Recent progresses in marine microbial-derived antiviral natural products. Arch. Pharm. Res. 43, 1215–1229 (2020). https://doi.org/10.1007/s12272-020-01286-3
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DOI: https://doi.org/10.1007/s12272-020-01286-3