Anti-Respiratory Syncytial Virus Compounds from Two Endophytic Fungi Isolated from Nigerian Medicinal Plants

Abstract

Background: Respiratory syncytial virus (RSV) is known to cause severe respiratory infections particularly in infants younger than 2 years of age. The only approved drug, ribavirin, is expensive and is not likely to improve therapeutic outcome, thereby necessitating the search for safer and more potent alternatives from natural sources such as endophytic fungi. The present study aimed to investigate the anti-RSV activity of compounds from endophytic fungi.

Methods: Two endophytic fungi Colletotrichum gloeosporioides and Pestalotiopsis thea were isolated from the fresh leaves of the host Nigerian plants Anthocleista djalonensis and Fagara zanthoxyloides, respectively. After fermentation in solid rice media, C. gloeosporioides afforded 4 known compounds 4-hydroxybenzoic acid (1), vanillic acid (2), ferulic acid (3) and N_b-acetyltryptamine (4) while P. thea afforded 3 known compounds chloroisosulochrin (5), ficipyrone A (6) and pestheic acid (7). The compounds were investigated for their anti-RSV activity using the HEP-2 cell lines and ribavirin as the standard drug.

Results: Compound 5 was found to show the strongest inhibition of the RSV with IC₅₀ of 4.22±1.03 µM (ribavirin 4.91±1.85 µM). Other compounds showed moderate inhibition of the virus (IC₅₀ ranging from 45.00±0.98 to 259.23±2.36 µM).

Conclusion: The results of the present study have shown that chloroisosulochrin (5), isolated from an endophytic fungus P. thea, possesses strong activity against RSV.

Key words

chloroisosulochrin - colletotrichum gloeosporioides - endophytic fungi - ficipyrone A - pestalotiopsis thea - pestheic acid - respiratory syncytial virus

• References

• 1 Hall CB, Weinberg GA, Iwane MK et al. The burden of respiratory syncytial virus infection in young children. New Engl J Med 2009; 360: 588-598
• 2 Nair H, Verma VR, Theodoratou E et al. An evaluation of the emerging interventions against respiratory syncytial virus (RSV)-associated acute lower respiratory infections in children. BMC Public Health 2011; 11 (Suppl. 03) article S30
• 3 Bloom-Feshbach K, Alonso WJ, Charu V et al. Latitudinal variations in seasonal activity of influenza and respiratory syncytial virus (RSV): a global comparative review. PLoS ONE 2013; 8 Article ID e54445
• 4 Henrickson H. Cost-effective use of rapid diagnostic techniques in the treatment and prevention of viral respiratory infections. Pediatric Annals 2005; 34: 24-31
• 5 Krilov LR. Respiratory syncytial virus disease: update on treatment and prevention. Expert Rev Anti Infect Ther 2011; 9: 27-32
• 6 Zhou H, Thompson WW, Viboud CG et al. Hospitalizations associated with influenza and respiratory syncytial virus in the United States, 1993–2008. Clin Infect Dis 2012; 54: 1427-1436
• 7 Bawage SS, Tiwari PM, Pillai S et al. Recent advances in diagnosis, prevention, and treatment of human respiratory syncytial virus. Adv Virol 2013; Article ID 595768 26 pages http://dx.doi.org/10.1155/2013/595768
• 8 Hall CB. Respiratory syncytial virus and parainfluenza virus. New Engl J Med 2001; 344: 1917-1928
• 9 Schickli JH, Dubovsky F, Tang RS. Challenges in developing a pediatric RSV vaccine. Hum Vaccin 2009; 5: 582-591
• 10 Ventre K, Randolph AG. Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children. Cochrane Database Syst Rev 2007; 1 CD000181
• 11 Osadebe PO, Odoh EU, Uzor PF. Natural products as potential sources of antidiabetic drugs. Br J Pharm Res 2014; 4: 2075-2095
• 12 Uzor PF, Ebrahim W, Osadebe PO et al. Metabolites from Combretum dolichopetalum and its associated endophytic fungus Nigrospora oryzae – Evidence for a metabolic partnership. Fitoter 2015; 105: 147-150
• 13 Umeokoli BO, Muharini R, Okoye FB et al. New C-methylated flavonoids and α-pyrone derivative from roots of Talinum triangulare growing in Nigeria. Fitoter 2016; 109: 169-173
• 14 Agbo MO, Lai D, Okoye FB et al. Antioxidative polyphenols from Nigerian mistletoe Loranthus micranthus (Linn.) parasitizing on Hevea brasiliensis. Fitoter 2013; 86: 78-83
• 15 Strobel G, Daisy B. Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 2003; 67: 491-502
• 16 Aly AH, Debbab A, Proksch P. Fungal endophytes: unique plant inhabitants with great promises. Appl Microbiol Biotechnol 2011; 90: 1829-1845
• 17 Zhang P, Li X, Wang B-G. Secondary metabolites from the marine algal-derived endophytic fungi: chemical diversity and biological activity. Planta Med 2016; doi: http://dx.doi.org/10.1055/s-0042-103496
• 18 Kaul S, Gupta S, Ahmed M et al. Endophytic fungi from medicinal plants: a treasure hunt for bioactive metabolites. Phytochem Rev 2012;
• 19 Lai D, Odimegwu DC, Esimone C et al. Phenolic compounds with in vitro activity against respiratory syncytial virus from the Nigerian lichen Ramalina farinacea. Planta Med 2013; 79: 1440-1446
• 20 Chen M, Shao C-L, Meng H et al. Anti-respiratory syncytial virus prenylated dihydroquinolone derivatives from the Gorgonian-derived fungus Aspergillus sp. XS 20090B15. J Nat Prod 2014; 77: 2720-2724
• 21 Esimone CO, Eck G, Duong TN et al. Potential anti-respiratory syncytial virus lead compounds from Aglaia species. Pharmazie 2008; 63: 768-773
• 22 Odimegwu DC, Grunwald T, Esimone CO. Anti-respiratory syncytial virus agents from phytomedicine. In: Resch B. (ed.). Human respiratory syncytial virus infection. InTech. 2011 . Available from http://www.intechopen.com/books/human-respiratorysyncytial-virus-infection/anti-respiratory-syncytial-virus-agents-from-phytomedicine
• 23 Li E, Tian R, Liu S et al. bioactive metabolites from the plant endophytic fungus Pestalotiopsis theae. J Nat Prod 2008; 71: 664-668
• 24 Tulliballi S, Seru G. Phytochemical investigation and evaluation of hepatoprotective and antimicrobial activities on the aerial parts of Barleria montana (Acanthaceae). Rasayan J Chem 2013; 6: 102-106
• 25 Chang SW, Kim KH, Lee IK et al. Phytochemical constituents of Bistorta manshuriensis. Nat Prod Sci 2009; 15: 234-240
• 26 Sajjadi SE, Shokoohinia Y, Moayedi N-S. Isolation and identification of ferulic acid from aerial parts of Kelussia odoratissima Mozaff. Jundishapur J Nat Pharm Prod 2012; 7: 159-162
• 27 Li Y, Li XF, Kim DS et al. Indole alkaloid derivatives, N_b-acetytrytamine and oxaline from a marine-derived fungus. Arch Pharm Res 2003; 26: 21-23
• 28 Shimada A, Takahashi I, Kawano T et al. chloroisosulochrin dehydrate, and pestheic acid, plant growth regulators, produced by Pestalotiopsis theae. Z Naturforsch 2001; 56b: 797-803
• 29 Liu S, Liu X, Guo L et al. 2H-pyran-2-one and 2H-furan-2-one derivatives from the plant endophytic fungus Pestalotiopsis fici. Chem Biodivers 2013; 10: 2007-2013
• 30 Jamila N, Khairuddean M, Khan SN et al. Phytochemicals from the bark of Garcinia hombroniana and their biological activities. Rec Nat Prod 2014; 8: 312-316
• 31 Shibata H, Kondo K, Katsuyama R et al. Alkyl gallates, intensifiers of -lactam susceptibility in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2005; 49: 549-555
• 32 Yang SW, Cordell GA. Metabolism studies of indole derivatives using a staurosporine producer, Streptomyces staurosporeus. J Nat Prod 1997; 60: 44-48
• 33 Klaiklay S, Rukachaisirikul V, Tadpetch K et al. Chlorinated chromone and diphenyl ether derivatives from the mangrove-derived fungus Pestalotiopsis sp. PSU-MA69. Tetrahedron 2012; 68: 2299-2305
• 34 Yu M, Snider BB. Syntheses of chloroisosulochrin and isosulochrin and biomimetic elaboration to maldoxin, maldoxone, dihydromaldoxin, and dechlorodihydromaldoxin. Org Lett 2011; 13: 4224-4227
• 35 Xu J. Bioactive natural products derived from mangrove-associated microbes. RSC Adv 2015; 5: 841-892
• 36 Allard PM, Leyssen P, Martin MT et al. Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri. Phytochem 2012; 84: 160-168
• 37 Allard PM, Martin MT, Dau ME et al. Trigocherrin A, the first natural chlorinated daphnane diterpene orthoester from Trigonostemon cherrieri. Org Lett 2012; 14: 342-345