Isolation of Thioinosine and Butenolides from a Terrestrial Actinomycetes sp. GSCW-51 and Their in Silico Studies for Potential against SARS-CoV-2.

In our continuous screening for bioactive microbial natural products, the culture extracts of a terrestrial Actinomycetes sp. GSCW-51 yielded two new metabolites, i. e., 5-hydroxymethyl-3-(1-hydroxy-6-methyl-7-oxooctyl)dihydrofuran-2(3H)-one (1), 5-hydroxymethyl-3-(1,7-dihydroxy-6-methyloctyl)dihydrofuran-2(3H)-one (2), and two known compounds; 5'-methylthioinosine (3), and 5'-methylthioinosine sulfoxide (4), which are isolated first time from any natural source, along with four known compounds (5-8). The structures of the new compounds were deduced by HR-ESI-MS, 1D and 2D NMR data, and in comparison with related compounds from the literature. Additionally, owing to the current COVID-19 pandemic situation, we also computationally explored the therapeutic potential of our isolated compounds against SARS-CoV-2. Compound 4 showed the best binding energies of -6.2 and -6.6 kcal/mol for Mpro and spike proteins, respectively. The intermolecular interactions were also studied using 2-D and 3-D imagery, which also supported the binding energies as well as put several insights under the spotlight. Furthermore, Lipinski's rule of 5 was used to predict the drug likeness of compounds 1-4, which indicated all compounds obey Lipinski's rule of 5. The study of bioavailability radars of the compounds 1-4 also confirmed their drug likeness properties where all the five crucial drug likeness parameters are in color area, which is safe to be used as drugs. Our isolation and computational findings highly encourage the scientific community to do further in vitro and in vivo studies of compounds 1-4.

Seven Compounds from Turmeric Essential Oil Inhibit Three Key Proteins Involved in SARS-CoV-2 Cell Entry and Replication in silico

Introduction: Turmeric rhizome (<italic>Cucurma longa</italic> L.) has showed great potential as a traditional drug in folk medicine of several countries. In light of the prominent use of turmeric rhizome in treating both respiratory and viral diseases, we aimed to dock major compounds from the essential oil of turmeric against three key proteins involved in COVID-19 cell entry and replication. Methods: The essential oil of turmeric rhizome was obtained using a hydrodistillation technique, and the chemical characterization of the oil was investigated using GC-MS/GC-FID. Then, main compounds were docked with the key proteins of COVID-19. Results: A total of 26 components were identified in the essential oil extracted from the rhizomes <italic>via</italic> GC-MS/GC-FID. Seven dominant compounds (turmerone (31.4%), ar-turmerone (16.1%), turmerol (14.6%), terpinolene (11.0%), α-zingiberene (5.2%), β-sesquiphellandrene (4.8%), and β-caryophyllene (3.5%)) were docked against COVID-19 main protease, papain-like protease (PLpro), spike protein and 3C-like protease (3CLpro), and the best inhibitor was picked according to the calculated binding affinity and non-bonding interactions with the protein active site. β-sesquiphellandrene and α-zingiberene showed highest besides the same binding affinity towards COVID-19 virus (−6.38 and −6.39kcal/mol, respectively). α-zingiberene was found to bind at the active site of the COVID-19 protein and interacted with different non-bonding interactions, while turmerol showed the highest affinity (−5.78kcal/mol) against CLpro enzyme by binding with Met165, Leu141, Met49, Ser144, Cys145, and Glu166 residues. Conclusion: The essential oil of turmeric harbors a blend of potentially bioactive compounds that may be considered as a good target against COVID-19 virus and warrants further experimental studies. [ABSTRACT FROM AUTHOR] Copyright of Journal of Computational Biophysics & Chemistry is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Antibiotic Potentiation of Natural Products: A Promising Target to Fight Pathogenic Bacteria.

Pathogenic microorganisms should be considered as the number one foe of human, as witnessed by recent outbreaks of coronavirus disease (COVID-19) and with bacteria no longer sensitive to existing antibiotics. The resistance of pathogenic bacteria and deaths attributable to bacterial infections is increasing exponentially. Bacteria used different mechanisms to counterattack to existing antibiotics, namely (i) enzymatic inhibition, (ii) penicillin-binding protein modification, (iii) porin mutations, (iv) efflux pumps and (v) molecular modifications of antibiotic targets. Developing new antibiotics would be time-consuming to address such a situation, thus one of the promising approaches is by potentiating existing antibiotics. Plants used synergism to naturally defend and protect themselves from microbes. Using the same strategy, several studies have shown that the combinations of natural products and antibiotics could effectively prolong the lifespan of existing antibiotics and minimize the impact and emergence of antibiotic resistance. Combining essential oils constituents, namely uvaol, ferruginol, farnesol and carvacrol, with antibiotics, have proved to be efficient efflux pump inhibitors. Plant-derived compounds such as gallic acid and tannic acid are effective potentiators of various antibiotics, including novobiocin, chlorobiocin, coumermycin, fusidic acid, and rifampicin, resulting in a 4-fold increase in the potencies of these antibiotics. Several lines of research, as discussed in this review, have demonstrated the effectiveness of natural products in potentiating existing antibiotics. For this reason, the search for more efficient combinations should be an ongoing process with the aim to extend the life of the ones that we have and may preserve the life for the ones that are yet to come.