Marine habitat is proving to be a rich source of novel microorganisms, particularly actinomycetes, whose metabolic products provide entirely new structural diversity with broad potential clinical applications [16, 17, 18, 19]. An array of novel compounds have been isolated from various marine organisms and evaluated for pharmacological properties. The screening of natural antiviral compounds from marine bacterial species has yielded positive outcome as there are over 40 compounds that are commercially made available in pharmacological markets. Several of the compounds have found applications in alternative antiviral medicines and some are being tested as potential antiviral drugs at the preclinical and clinical stages [20]. Musacin C (Streptomyces griseovirdis), Fattiviracin A1(Streptomyces griseovirdis), FK 506 (Streptomyces tsukubaensis), Cyclomarin A (Streptomyces sp.), Resistomycin (Streptomyces corchorusii), Benzastatin C (Streptomyces nitrosporeus), MM461156 (Actinomadurapelletieri), Antimycin (S.kaviengensis) etc produced by marine actinomycetes have exhibited potential antiviral effect against HSV-1, VZV, HIV, Orthopox, White Spot Syndrome virus, Hepatitis C, Western Equine Encephalitis virus etc. Their antiviral mechanisms broadly include the inactivation of the viral particles, inhibition of viral entry into host cells and inhibition of viral replication. These products continue to provide new drug leads for pharmaceutical development. However, reports on the compounds from natural sources especially marine actinomycetes exhibiting anti-Influenza viral activity are scarce [21].
The immense capability of microorganisms presents an unrivalled opportunity to explore their unique properties towards the discovery of novel therapeutic agents. In this report, the potential anti-influenza feature of the solvent fractions derived from a marine actinomycete S. jiangxiensis IMA1is explored in-vitro using MDCK cell line susceptible for influenza A/(H1N1)pdm09. This study optimizes the non-toxic dose of the ethyl fraction which was also found to possess anti-influenza activity as determined by antiviral studies. The ethyl acetate fraction was found to be more effective in terms of displaying non toxicity than the other solvent fractions such as methanol, ethanol, and aqueous derived from the marine actinomycete. Due to their toxic features as revealed by MTT assay and microscopic observations, further studies on evaluation of antiviral features were not planned for other fractions. Ethyl acetate is reported to be widely used for extracting the extra cellular antimicrobial secondary metabolites from actinomycetes [22, 23, 24, 25].
In the present study, it was shown that the compounds in the ethyl acetate fraction were found to hinder the early stage of influenza A virus lifecycle through cell susceptibility and fluorescence microscopy studies and reduction in viral load was also confirmed by amplification inhibition assay. These promising early findings necessitate to conduct further studies on characterization of antiviral compound in the fraction and to propose the mechanism of antiviral activity. Previously few studies report such findings of antiviral features [26, 27, 28, 29].
Most important finding in the present study is that this novel fraction has inhibitory effects on oseltamivir resistant strains of influenza viruses, suggesting that its antiviral activity may involve a different mode of action from current available antiviral agents besides its utility potential for treating oseltamivir resistant strains. Results from qRT-PCR also supported the findings from the viral foci reduction assays and demonstrated the significant reduction in Flu A/(H1N1)pdm09 virus specific RNA, suggesting that the fraction may probably target the virus replication machinery, mainly by inhibiting the RNA polymerase [30, 31]. Recent reports suggest the emergence of drug resistant pathogens and urge to search for the novel drugs against such pathogens. Takahashi and Nakashimastated the possibility of finding new and efficient bioactive metabolites from actinobacteria in under-explored resources [32].