COVID-19 pandemic caused by the SARS-CoV-2 virus has led to a worldwide crisis. In view of emerging variants time to time, there is a pressing need of effective COVID-19 therapeutics. Setomimycin, a rare tetrahydroanthracene antibiotic, remained unexplored for its therapeutic uses. Herein, we report our investigations on the potential of setomimycin as COVID-19 therapeutic. Pure setomimycin was isolated from
Streptomyces
sp. strain RA-WS2 from NW Himalayan region followed by establishing in silico as well as in vitro anti-SARS-CoV-2 property of the compound against SARS-CoV-2 main protease (M
pro
). It was found that the compound targets M
pro
enzyme with an IC
50
value of 12.02 ± 0.046 μM. The molecular docking study revealed that the compound targets Glu166 residue of M
pro
enzyme, hence preventing dimerization of SARS-CoV-2 M
pro
monomer. Additionally, the compound also exhibited anti-inflammatory and anti-oxidant property, suggesting that setomimycin may be a viable option for application against COVID-19 infections.
Graphical abstract
Consistent production of bioactives from microbial sources remains a big challenge for fermentation based bio-processes. Setomimycin, a rare 9,9'-bianthrylanthracene antibiotic reported to be active against Gram positive bacteria i.e. Staphyloccocus aureus, Bacillus subtilis, Bacillus cereus, and Mycobacterium smegmatis, including mycobacteria is one of the least exploited antibiotic. Present work aims to enhance and maximize setomimycin production using One Factor at a Time (OFAT) approach, followed by Taguchi L9 orthogonal array (OA) design in 30L fermenter. Four most influential parameters, namely carbon source, nitrogen source, air and agitation were selected for optimization studies. The optimized production medium supplemented with 150 g/L glycerol and 7.5 g/L soyabean meal with an agitation rate of 100 RPM and air flow rate of 20 LPM (Liters Per Minute) resulted in 675 mg/L setomimycin production within 96–108 h of fermentation as compared to the initial production i.e. 40 mg/L. Thus, an overall enhancement of 16.8 folds was achieved in setomimycin production after optimization in 30L fermenter.
Graphical Abstract
Background: COVID-19 pandemic has forced the human population to rethink over the lifestyle and food habits being followed by them. During the current scenario, when cases of more virulent new strain are emerging and specific treatment are still underway, we must look back to the Darvin’s theory of “Survival of the fittest” and in order to sustain the pandemic, we must follow the rule “Prevention is better than cure”. Traditional Medicinal System can bring possible solution including prevention and control of COVID-19. Humic substances have been used for antiviral activities, signifying that it has potential applications in the management and prevention of infectious diseases.
Summary: Present article is focused on the assessment of the naturally occurring humic substances, which are major constituents of Shilajit, being used in traditional system of medicine and can be used against for the prevention of COVID-19.
Key message: Humic substances not only improve the immune system, but also have anti-inflammatory, antioxidant and antiviral activities against human RNA viruses. Therefore, while the entire world is preparing to deal with alarming threat of community spread of COVID-19, Humic substances may play a vital role in improving the innate immunity for prevention and management of SARS-CoV-2 infection
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