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Ribosome Inactivating Proteins (RIPs) act by irreversibly depurinating the 28S rRNA ricin-sarcin loop (SRL) of the eukaryotic ribosome resulting in protein synthesis inhibition. In general, they consist of two variants: Type I which is single chained (∼30 kDa), and Type II, a more toxic variant which is a Type I N-glycosidase chain covalently linked to a lectin chain. These proteins are believed to play a pivotal role in defence mechanisms. Intriguingly, non-toxic variants of such toxic proteins do exist in nature. To explore their mode of action, in the present study we have selected three toxic (Ricin, Ebulin and HmRIP) as well as two non-toxic (BGSL and SGSL) RIPs and performed molecular docking and molecular dynamic simulations with the SRL loop. This study throws light on the structural stability and plasticity of the toxic and non-toxic RIP complexes. Furthermore, analysis of the active site cavity volume and binding free energy calculations reveal that the SRL, particularly the specific adenine (A4605), is relatively unstable in the case of non-toxic RIPs which is also supported by the free binding energy calculations, and the pocket size analysis indicates the abnormal increase in active site cavity volume of non-toxic RIPs with time. This first-of-its-kind comprehensive study of toxic and non-toxic RIPs gives insights about the mode of action and the dynamic nature of their interaction with the SRL loop. These observations will be helpful in the development of toxoids against RIPs and also in designing novel therapeutic approaches against human diseases.

Plant species from the genus Andrographis were used in Ayurveda and in other folklore medicines for treating ailments for centuries. In this study, we have hypothesized to evaluate the secondary metabolites as potent anti-inflammatory agents from the genus Andrographis. A library of secondary metabolites of the said genus was curated from the PubChem database and was subjected to energy minimization using UCSF Chimera software employing the AMBER force field. Initially, molecular docking was performed to evaluate the binding affinity of the curated library against the enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 5-Lipoxygenase (5-LOX) using AutoDock Vina. This resulted in shortlisting of two metabolites Echioidinin 5-O-glucoside was bound and 5,2',6'-Trihydroxy-6,7,8-trimethoxy flavone 2'-O-glucoside with high binding affinity than standard drugs Ibuprofen and Zileuton. In addition, molecular dynamic simulation studies confirm that these compounds form relatively more stable complexes than standard drugs with the above-said enzymes. The free binding energy values using MMGBSA of the above said ligands with COX-1, COX-2, and 5-LOX were found to be -49.18 kcal/mol, -38.60 kcal/mol, and -54.27 kcal/mol respectively, Whereas the standards have -21.77 kcal/mol, -9.96 kcal/mol, and -10.29 kcal/mol. Moreover, the in-silico ADMET analysis confirms the druggability of the shortlisted compounds. Later, this work will act as a base for in-vitro and in-vivo experimental studies to validate the anti-inflammatory potential of the same.Communicated by Ramaswamy H. Sarma.

The prefatory protein-glycan interaction and stabilizing protein-protein interaction of severe acute respiratory syndrome viruses with angiotensin-converting enzyme 2 play a significant role in complex formation thereby promoting endocytosis. The microevolution of SARS-CoV-2 over a period of time has a significant role in increasing the affinity of receptor-binding domain against angiotensin converting-enzyme 2. In this study, we have corroborated the vitality of acquired SNPs over a period of time with increased affinity by using docking studies. The results indicate that the virus modulates the undesirable glycosylation sites by a series of substitution and deletion mutations. It uses bulky residues such as Tyr/Phe for dynamic arrest for quick stabilization of the complex, and Lys residues for stabilizing via hydrogen bond formation besides increasing the binding affinity to ease the cell entry.Communicated by Ramaswamy H. Sarma.

The adhesive properties, as measured by bulk tack analysis, are found to decrease in blends of isomerically pure Sc3N@I(h)-C80 metallic nitride fullerene (MNF) and polystyrene-block-polyisoprene-block-polystyrene (SIS) copolymer pressure-sensitive adhesive under white light irradiation in air. The reduction of tack is attributed to the in situ generation of 1O2 and subsequent photooxidative cross-linking of the adhesive film. Comparisons are drawn to classical fullerenes C60 and C70 for this process. This work represents the first demonstration of 1O2 generating ability in the general class of MNFs (M3N@C80). Additional support is provided for the sensitizing ability of Sc3N@I(h)-C80 through the successful photooxygenation of 2-methyl-2-butene to its allylic hydroperoxides in benzene-d(6) under irradiation at 420 nm, a process that occurs at a rate comparable to that of C(60). Photooxygenation of 2-methyl-2-butene is found to be influenced by the fullerene sensitizer concentration and O2 flow rate. Molar extinction coefficients are reported for Sc3N@I(h)-C80 at 420 and 536 nm. Evaluation of the potential antimicrobial activity of films prepared in this study stemming from the in situ generation of 1O2 led to an observed 1 log kill for select Gram-positive and Gram-negative bacteria.

The yield of Sc3N@C80 metallofullerene and fullerene extract is dramatically increased via filling cored graphite rods with copper and Sc2O3 only; when compared to 100% Sc2O3 packed rods, improvements of factors of approximately 3 and approximately 5 have been achieved for Sc3N@C80 and fullerene extract produced, respectively, with the weight percent of Cu added to the rod affecting the type and amount of fullerene produced.