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Since the emergency of coronavirus disease 2019, no specific drug has been developed within the fighting program against its spread. In Cameroon, it has been reported that the dish “yellow soup” can significantly curb the progress of the disease, while no chemical investigations have been done so far to support that conclusion. Chemical investigations of four selected spices of that dish led to the isolation of a total of 44 distinct pure compounds, which were identified using spectroscopic data. Furthermore, the docking scores of the isolated compounds were inspected by AutoDock4.2.6 software toward SARS-CoV-2 multi-targets involving main protease (Mpro), helicase, papain-like protease (PLpro), and human angiotensin‐converting enzyme 2 (ACE2). The most potent isolated compounds underwent molecular dynamics (MD) simulations over 100 ns. Stigmasterol demonstrated outstanding potency toward Mpro and PLpro with ΔG binding values of −35.6 and −36.6 kcal/mol, respectively, compared to nirmatrelvir. Nevertheless, 3β-taraxeryl acetate revealed good binding affinity against helicase and lupeol unveiled superior binding energy toward ACE2 compared to nirmatrelvir. Post-MD analyses manifested great steadiness of the isolated compounds within the binding pockets of SARS-CoV-2 targets throughout 100 ns MD simulations. Stigmasterol, 3β-taraxeryl acetate, and lupeol are recommended for further in vivo/in vitro tests toward SARS-CoV-2 multi-targets.

Phytochemical investigation of a methanolic extract derived from the oleo-gum resin of Commiphora mukul resulted in the isolation of seven pregnene-type steroids (1 - 7), including a new compound named commukulsterol A (1). Their structures were decided by extensive analyses of 1D, 2D-NMR and Mass spectra. The relative configurations of commukulsterols A (1) and B (2) were determined via DFT calculations of their 1H and 13C chemical shifts, followed by DP4+ statistical analysis. Absolute configurations were then decided by biogenetic similarities and specific rotations. Such analyses led to the revision of the structure of 2 , initially elucidated as 20 S -acetyloxy-4-pregnene-3,16-dione, to pro-20 R. 1 - 7 showed varying inhibitory effects on LPS-induced NO release in RAW264.7 macrophages, with IC 50 values ranging from 7.6 to 53.9 μM for (1 - 6) , while 7 didn't show activity up to 100 μM. On the other hand, molecular docking revealed that 3 & 4 could bind to the catalytic site of inducible nitric oxide synthase (iNOS). Moreover, molecular dynamics simulation of 3 & 4 in association with iNOS were examined for 200 ns, revealing adequate stability. ADMET analysis indicated good oral bioavailability and drug-like properties. The observed chemical profile highlighted a unique chemical relationship between Burseraceae and Simaroubaceae families. [Display omitted] • Seven pregnane steroids were isolated from the oleo gum resin of Commiphora muckul. • A new compound and revised structure of a known compound were decided. • Structures were identified by NMR & MS, while configurations by DFT calculations. • Compounds were tested for their anti-inflammatory activity and ADMET properties were predicted. • Molecular docking asserted by molecular dynamics evaluated the activity on molecular level. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis is a lethal human pathogen, with the key flavoenzyme for catalyzing bacterial cell-wall biosynthesis, decaprenylphosphoryl-D-ribose oxidase (DprE1), considered an Achilles heal for tuberculosis (TB) progression. Inhibition of DprE1 blocks cell wall biosynthesis and is a highly promising antitubercular target. Macozinone (PBTZ169, a benzothiazinone (BTZ) derivative) is an irreversible DprE1 inhibitor that has attracted considerable attention because it exhibits an additive activity when combined with other anti-TB drugs. Herein, 754 BTZ analogs were assembled in a virtual library and evaluated against the DprE1 target using a covalent docking approach. After validation of the employed covalent docking approach, BTZ analogs were screened. Analogs with a docking score less than –9.0 kcal/mol were advanced for molecular dynamics (MD) simulations, followed by binding energy evaluations utilizing the MM-GBSA approach. Three BTZ analogs–namely, PubChem-155-924-621, PubChem-127-032-794, and PubChem-155-923-972– exhibited higher binding affinities against DprE1 compared to PBTZ169 with ΔGbinding values of –77.2, –74.3, and –65.4 kcal/mol, versus –49.8 kcal/mol, respectively. Structural and energetical analyses were performed for the identified analogs against DprE1 throughout the 100 ns MD simulations, and the results demonstrated the great stability of the identified BTZ analogs. Physicochemical and ADMET characteristics indicated the oral bioavailability of the identified BTZ analogs. The obtained in-silico results provide promising anti-TB inhibitors that are worth being subjected to in-vitro and in-vivo investigations. [ABSTRACT FROM AUTHOR]

A DNA tumor virus called Epstein-Barr virus (EBV) is the cause of 1-2% of human cancers. EBV-associated carcinogenesis is caused by a persistent latent infection. The shortage of antiviral medications or vaccinations to control the virus led to a significant percentage of critically sickness individuals needing to be hospitalized. In the absence of an effective vaccine and approved drug, there is an immediate need for treatments that can combat EBV infection. Epstein Barr nuclear antigen 1 (EBNA1) is continually expressed in all malignancies linked to EBV; it is a desirable target for curative interference. Herein, natural product compounds from the Nuclei of Bioassays, Ecophysiology and Biosynthesis of Natural Products (NuBBE) database were mined to identify potent EBNA1 inhibitors. The performance of the molecular docking technique was initially assessed in expecting the ligand-target binding pose according to the available experimental data. On the basis of the estimated docking protocol, the NuBBE database was virtually screened toward the EBNA1 protein, and the natural compounds with binding scores less than KWG (calc. − 7. 8 kcal/mol) were subjected to molecular dynamics (MD) simulations followed by binding energy (Δ G binding ) calculation using MM/GBSA approach. Based on binding energy computations, NuBBE1460 revealed superior Δ G binding with a value of − 3 6. 2 kcal/mol, compared to KWG (calc. − 3 2. 4 kcal/mol). Post-MD analyses displayed a high steadiness of NuBBE1460 within the EBNA1 protein binding pocket. Furthermore, the physicochemical, pharmacokinetic and toxicity features of the identified compound were predicted, demonstrating high degrees of its oral bioavailability. The energetical and geometrical properties of NuBBE1460 were calculated using the DFT method. Conclusively, this study offers NuBBE1460 obtained from natural sources as a lead EBNA1 inhibitor for future investigation and development as a therapeutic for EBV. NuBBE database was virtually screened as potent EBNA1 inhibitors using in-silico calculations. Compared to KWG, a reference inhibitor, NuBBE1460 exhibited better binding affinity against EBNA1. NuBBE1460 demonstrated promising stability in complex with EBNA1 and unveiled good oral bioavailability. [ABSTRACT FROM AUTHOR]

The Red Sea soft coral Sarcophyton acutum ethyl acetate extract has afforded one new cembranoid; sarcacutumolid A (1), along with six known metabolites have been isolated from S. acutum for the first time (2-7). Chemical structures were elucidated by employing several spectroscopic analyses. The cytotoxic potential of the isolated compounds was assessed against four human cancer cell lines; hepatocellular (HepG2), cervical (HeLa), breast (MCF-7) and colorectal cancer (Colo-205). Sarcacutumolid A (1) and gorgosterol (7) inhibited colorectal cancer cell proliferation in a concentration-dependent manner with IC50 values of 35.5 and 44.0 μM, respectively. [ABSTRACT FROM AUTHOR]