Priyanka Saha

Ruta chalepensis L. (Rutaceae), a perennial herb with wild and cultivated habitats, is well known for its traditional uses as an anti-inflammatory, analgesic, antipyretic agent, and in the treatment of rheumatism, nerve diseases, neuralgia, dropsy, convulsions and mental disorders. The antimicrobial activities of the crude extracts from the fruits, leaves, stem and roots of R. chalepensis were initially evaluated against two Gram-positive and two Gram-negative bacterial strains and a strain of the fungus Candida albicans. Phytochemical investigation afforded 19 compounds, including alkaloids, coumarins, flavonoid glycosides, a cinnamic acid derivative and a long-chain alkane. These compounds were tested against a panel of methicillin-resistant Staphylococcus aureus (MRSA) strains, i.e., ATCC 25923, SA-1199B, XU212, MRSA-274819 and EMRSA-15. The MIC values of the active compounds, chalepin (9), chalepensin (10), rutamarin (11), rutin 3′-methyl ether (14), rutin 7,4′-dimethyl ether (15), 6-hydroxy-rutin 3′,7-dimethyl ether (16) and arborinine (18) were in the range of 32–128 µg/mL against the tested MRSA strains. Compounds 10 and 16 were the most active compounds from R. chalepensis, and were active against four out of six tested MRSA strains, and in silico studies were performed on these compounds. The anti-MRSA activity of compound 16 was comparable to that of the positive control norfloxacin (MICs 32 vs 16 μg/mL, respectively) against the MRSA strain XU212, which is a Kuwaiti hospital isolate that possesses the TetK tetracycline efflux pump. This is the first report on the anti-MRSA property of compounds isolated from R. chalepensis and relevant in silico studies on the most active compounds.

Emerging shreds of evidence suggest that tumor-associated macrophages (TAMs) modulate various hallmarks of cancer during tumor progression. Tumor microenvironment (TME) prime TAMs to execute important roles in cancer development and progression, including angiogenesis, matrix metalloproteinases (MMPs) secretion, and extracellular matrix (ECM) disruption. MicroRNAs (miRNAs) are critical epigenetic regulators, which modulate various functions in diverse types of cells, including macrophages associated with TME. In this review article, we provide an update on miRNAs regulating differentiation, maturation, activation, polarization, and recruitment of macrophages in the TME. Furthermore, extracellular miRNAs are secreted from cancerous cells, which control macrophages phenotypic plasticity to support tumor growth. In return, TAMs also secrete various miRNAs that regulate tumor growth. Herein, we also describe the recent updates on the molecular connection between tumor cells and macrophages. A better understanding of the interaction between miRNAs and TAMs will provide new pharmacological targets to combat cancer.

SARS-CoV-2 uses RBD of Spike (S) protein to attach with human cell via ACE2 receptor, followed by protease priming at S1/S2 site resulted in host cell entry and pathogenesis. In this context, we focused our aim in studying natural mutations harboring in Spike protein of SARS-CoV-2. We have analyzed 420 COVID-19 cases. G476S and V483G mutation are observed which lies in the RBD region where as the prevalent D614G mutation is observed in the vicinity of S1/S2 site. Interestingly MD simulation supports strong favorable interaction of ACE2 with RBD region containing V483A mutation as compared to G476S and reference wild Wuhan S protein. Radius of gyration analysis also showed high degree of compactness in V483A. The landscape plot and Gibbs free energy also support our findings. Overall, our study indicates that V483G in the RBD region can enhance its binding with the human ACE2 receptor. Interestingly D614G mutation in vicinity of S1/S2 region introduced a new cleavage site specific for a serine protease elastase that is anticipated to broaden the virus host cell tropism. Hence, both V483A and D614G mutations led to enhanced and broaden the virus host cell entry and transmission of the disease. Further epitope mapping analysis revealed G476S and D614G mutations as antigenic determinants and thus these mutations are important while designing a therapeutics vaccine or chimeric antibody. This finding will help in further understanding the role of such arising mutations in modulating immunogenicity, viral tropism and pathogenesis of the disease, which in lieu will help in designing vaccine more precisely to mitigate pandemic COVID-19.