Volume 79, Issue 1-2

Boceprevir drug is a ketoamide serine protease inhibitor with a linear peptidomimetic structure that exhibits inhibition activity against 2019-nCoV main protease. This paper reports electronic properties of boceprevir and its molecular docking as well as molecular dynamics simulation analysis with protein receptor. For this, the equilibrium structure of boceprevir has been obtained by DFT at B3LYP and ωB97XD levels with 6-311+G(d,p) basis set in gas and water mediums. HOMO–LUMO and absorption spectrum analysis have been used to evaluate the boceprevir’s toxicity and photosensitivity, respectively. Molecular docking simulation has been performed to test the binding affinity of boceprevir with 2019-nCoV M PRO ; which rendered a variety of desirable binding locations between the ligand and target protein’s residue positions. The optimum binding location has been considered for molecular dynamics simulation. The findings have been addressed to clarify the boceprevir drug efficacy against the 2019-nCoV M PRO .

SARS-CoV-2 nsp12, the RNA-dependent RNA-polymerase plays a crucial role in virus replication. Monitoring the effect of its emerging mutants on viral replication and response to antiviral drugs is important. Nsp12 of two Egyptian isolates circulating in 2020 and 2021 were sequenced. Both isolates included P323L, one included the A529V. Tracking A529V mutant frequency, it relates to the transience peaked C.36.3 variant and its parent C.36, both peaked worldwide on February–August 2021, enlisted as high transmissible variants under investigation (VUI) on May 2021. Both Mutants were reported to originate from Egypt and showed an abrupt low frequency upon screening, we analyzed all 1104 nsp12 Egyptian sequences. A529V mutation was in 36 records with an abrupt low frequency on June 2021. As its possible reappearance might obligate actions for a candidate VUI, we analyzed the predicted co-effect of P323L and A529V mutations on protein stability and dynamics through protein structure simulations. Three available structures for drug–nsp12 interaction were used representing remdesivir, suramin and favipiravir drugs. Remdesivir and suramin showed an increase in structure stability and considerable change in flexibility while favipiravir showed an extreme interaction. Results predict a favored efficiency of the drugs except for favipiravir in case of the reported mutations.

Verbascum sinaiticum is locally used to treat wound, stomachache, viral infection, cancer, sunstroke fever, abdominal colic, diarrhea, hemorrhage, anthrax, and hepatitis. The objective of this study was to identify the compounds and to evaluate the antimicrobial and antioxidant activity of the extracts and isolated compounds from V. sinaiticum . The 1 H-NMR, 13 C-NMR, and DEPT-135 were used to elucidate the structures of isolated compounds. Essential oils were extracted by hydrodistillation method and their chemical analyses were performed by GC-MS. The broth microdilution method was used to evaluate the antimicrobial activity. The radical scavenging activity of the extracts and isolated compounds were evaluated using DPPH method. Silica gel column chromatographic separation of root extracts afforded seven known compounds: 3′-(4′′-methoxy phenyl)-3′-oxo-propionyl hexadecanoate ( 1 ), harpagoside ( 2 ), pulverulentoside I ( 3 ), scrophuloside B4 ( 4 ), scropolioside A ( 5 ), scropolioside-D2 ( 6 ), and harpagide 6- O -β-glucoside ( 7 ), which are all reported from this species for the first time. The EO extracts from leaves and roots were the most susceptible to Streptococcus agalactiae , with a 2 mg/mL MIC. The EO from roots was effective against Candida albicans and Trichophyton mentagrophytes , with a MIC of 8 mg/mL. The MeOH and CH 2 Cl 2 /CH 3 OH (1:1) root extracts showed the maximum activity against S. epidermidis with MIC values of 0.25 mg/mL. The strongest antibacterial effects were demonstrated against Staphylococcus epidermidis , which exhibited a 0.0625 mg/mL MIC for compound 1 . The strongest radical scavenging activity was exhibited by the methanol extract (IC 50 = 3.4 μg/mL), and compounds 4 , 6 , 5 , 3 , 7 , and 2 with IC 50 values of 3.2, 3.38, 3.6, 3.8, 4.2, and 4.7 μg/mL, respectively, in comparison with ascorbic acid (IC 50 = 1.3 μg/mL). The results of the molecular docking analysis of compounds revealed minimal binding energies range from −38.5 to −43.1 kJ/mol, −33.1 to −42.7 kJ/mol, −34.7 to −39.3.7 kJ/mol, −25.5 to −37.6 kJ/mol against human myeloperoxidase (PDB ID: 1DNU), murA enzyme (PDB ID: 1UAE), human topoisomerase II β (PDB ID: 4fm9), S. epidermidis FtsZ (PDB number: 4M8I) proteins, respectively. The docking results and the in vitro antibacterial activity are in good agreement. These findings show that the isolated compounds 2 – 7 can act as potential antioxidants and strong antibacterials against Staphylococcus aureus and S. epidermidis . As a result, V. sinaiticum root extracts have the potential to be effective in treating diseases caused by bacteria and free radicals, as long as further investigation has been suggested for the ultimate decision of this plant’s potential candidate.

A set of cyclopenten-[ g ]annelated isoindigos ( 5a–g ) has been prepared and tested for their in vitro antiproliferative activities against MCF-7 and HL60 cells. Among, the N -1-methyl-5′-nitro derivative ( 5g ) displayed the highest activity against HL60 cells (IC 50  = 67 nM) and acted as the most potent Flt3 inhibitor. Compounds 5d–g exhibited moderate activity against MCF-7 (IC 50  = 50–80 μM).