Bruguiera gymnorhiza (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective

Abstract

The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, Bruguiera gymnorhiza (L.) Lam. (B. gymnorhiza) collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70603, methicillin-resistant Staphylococcus aureus ATCC 43300 (MRSA), Salmonella enteritidis ATCC 13076, Sarcina lutea ATCC 9341, Proteus mirabilis ATCC 25933, Bacillus cereus ATCC 11778 and Candida albicans ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKVMC-MR766NIID (ZIKVGFP) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that Bruguiera twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19–0.39 mg/mL. BTE showed partial synergy effects against MRSA and Pseudomonas aeruginosa when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both Bruguiera root aqueous and Bruguiera fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in B. gymnorhiza. From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from B. gymnorhiza to fight ZIKV and microbial infections in the future.

Chemical Constituents and Biological Activities of Bruguiera Genus and Its Endophytes: A Review

“…Currently, 17 steroids (Table 5 and Figure 6) have been identified in the Bruguiera plants and their endophytic fungi. These compounds encompass three types: cholestrol (153), stigmastanol (154)(155)(156)(157)(158), and ergosterol (159)(160)(161)(162)(163)(164)(165)(166)(167)(168)(169), specifically noting the significance of two ergostanes (168-169) with a rearranged tetracyclic skeleton.…”

Exploring the Mangrove Fruit: From the Phytochemicals to Functional Food Development and the Current Progress in the Middle East

“…The aqueous extract contains polyphenols that disrupt the lipid membrane (outer membrane) of the flavivirus [ 50 ]. The protein for the cell-binding receptor of ZIKV is targeted by cryptochlorogenic acid from the extract, leading to the virus’ death [ 51 ]. Moreover, the aqueous extract of R. mangle showed activity against various bacteria and depicted the cytotoxicity against human fibrosarcoma cell line HT1080 [ 52 ].…”

Antimicrobial Secondary Metabolites from the Mangrove Plants of Asia and the Pacific

“…Plants in the Rhizophoraceae are tanniferous and have antibacterial activities as in Bruguiera cylindrica (L.) Bl. [ 71 ], Bruguiera gymnorhiza (L.) Savigny [ 72 ], Bruguiera sexangula (Lour.) Poir., Ceriops decandra Griff.)…”

“…pumilus with a MIC value of 15.6 µg/mL by the benzene extract of the wood of C. decandra [ 94 ]. The presence of tannins and phenolics most probably account for the antiviral effects observed in B. cylindrica , Rhizophora mucronata Lam., R. apiculata , B. gymnorhiza [ 72 ], C. decandra [ 68 ]. Other examples of water soluble antibacterials are the cyclohexylideneacetonitrile derivatives from B. gymnorhiza , which strongly repressed HBV [ 69 ].…”