Vaccines and therapeutic antibodies are the most crucial components of anthrax prophylaxis (pre- and post-exposure) and treatment. The improvement in the availability and safety profile of vaccines...

A combination of docking approaches, scoring functions, molecular dynamic simulation, and literature mining have been employed to screen readily available natural products (unique 27256 chemical entities, 598435 unique compounds), which can inhibit the SARS-CoV-2 main protease. Theaflavin digallate, a major constituent of black tea, has been observed to be as three top hits after the virtual screening of 598435 unique compounds. The main protease-theaflavin digallate complex appeared to be in the metastable stage and interact with critical active site residues of the main protease during molecular dynamics simulation for 200 ns. Invitro evidence on main protease inhibition of 2003 SARS-CoV by theaflavin digallate is available in the scientific literature. As evident by the dynamics of intermolecular interactions, theaflavin digallate, forms approximately three hydrogen bonds with Glu166 of main protease, mostly through hydroxyl groups in the benzene ring of benzo(7) annulen-6-one. Glu166 is the most critical amino acid for main protease dimerization, which in turn, is necessary for catalytic activity. We have employed chloroquine and epigallocatechin gallate (green tea component) as a control set. Based on computational molecular interaction and data available in scientific literature, theaflavin digallate can inhibit the main protease of SARS-CoV-2.

The role of pharmacogenetics in the personalization of tamoxifen therapy has relevance in the management of breast cancer. Since Tamoxifen is a pro-drug, genetic polymorphism in Phase I and Phase II drug metabolizing enzymes involved in the bioconversion of tamoxifen to therapeutically active metabolites is critical in determining therapeutic efficacy and adverse drug reactions of the therapy in breast cancer patients. In this review, the role of pharmacogenetics in the personalization of tamoxifen therapy has been discussed. Since, metabolism of tamoxifen by Cytochrome P450 2D6 is significant in determining the therapeutic efficacy of the drug, most of the clinical evidence on tamoxifen pharmacogenetics have been correlated with cytochrome p450 2D6 genetic polymorphism. However, there is discordance in the clinical data, and one of the reasons is the incomplete analysis of all the alleles of cytochrome p450 2D6. International Tamoxifen Pharmacogenomics Consortium has been formed to assess the discordance. There are also clinical evidences associating genetic polymorphism in cytochrome P450 3A, 2C9, 2C19, Uridine diphosphate –glucuronosyltransferases and Sulfotransferases with clinical outcome of tamoxifen therapy. However, associations of genetic polymorphism in cytochrome P450 3A, 2C9, 2C19, Uridine diphosphate –glucuronosyltransferases and Sulfotransferases with clinical outcome in populations of different ethnicity are unexplored. Evidences on the association of genetic polymorphisms and the clinical outcome have been summarized in the Table. Since cost, statistically significant sample population size, labor and ethical issues are the major concerns of a pharmacogenetic investigation; the significance of bottom-up approach in pharmacogenetics has been discussed.

Ethnopharmacological Relevance: Gastrointestinal anthrax, a disease caused by Bacillus anthracis , remains an important but relatively neglected endemic disease of animals and humans in remote areas of the Indian subcontinent and some parts of Africa. Its initial symptoms include diarrhea and stomachache. In the current study, several common plants indicated for diarrhea, dysentery, stomachache or as stomachic as per traditional knowledge in the Indian subcontinent, i.e. , Aegle marmelos (L.) Correa (Bael), Allium cepa L. (Onion), Allium sativum L. (Garlic) , Azadirachta indica A. Juss. (Neem), Berberis asiatica Roxb. ex DC. (Daruharidra), Coriandrum sativum L. (Coriander), Curcuma longa L. (Turmeric), Cynodon dactylon (L.) Pers. (Bermuda grass), Mangifera indica L. (Mango), Morus indica L. (Black mulberry), Ocimum tenuiflorum L. (Ocimum sanctum L. , Holy Basil), Ocimum gratissimum L. (Ram Tulsi), Psidium guajava L. (Guava), Zingiber officinale Roscoe (Ginger), were evaluated for their anti- Bacillus anthracis property. The usage of Azadirachta indica A. Juss. and Curcuma longa L. by Santals (India), and Allium sp. by biblical people to alleviate anthrax-like symptoms is well documented, but the usage of other plants is traditionally only indicated for different gastrointestinal disturbances/conditions. Aim of the Study: Evaluate the above listed commonly available edible plants from the Indian subcontinent that are used in the traditional medicine to treat gastrointestinal diseases including those also indicated for anthrax-like symptoms for the presence of potent anti- B. anthracis activity in a form amenable to use by the general population in the endemic areas. Materials and Methods: Aqueous extracts made from fourteen plants indicated above were screened for their anti- B. anthracis activity using agar-well diffusion assay (AWDA) and broth microdilution methods. The Aqueous Garlic Extract (AGE) that displayed most potent anti- B. anthracis activity was assessed for its thermostability, stability under pH extremes encountered in the gastrointestinal tract, and potential antagonistic interaction with bile salts as well as the FDA-approved antibiotics used for anthrax control. The bioactive fractions from the AGE were isolated by TLC coupled bioautography followed by their characterization using GC-MS. Results: Garlic ( Allium sativum L.) extract was identified as the most promising candidate with bactericidal activity against B. anthracis . It consistently inhibited the growth of B. anthracis in AWDA and decreased the viable colony-forming unit counts in liquid-broth cultures by 6-logs within 6-12 h. The AGE displayed acceptable thermostability (>80% anti- B. anthracis activity retained on incubation at 50°C for 12 h) and stability in gastric pH range (2-8). It did not antagonize the activity of FDA-approved antibiotics used for anthrax control. GC-MS analysis of the TLC separated bioactive fractions of AGE indicated the presence of previously unreported constituents such as phthalic acid derivatives, acid esters, phenyl group-containing compounds, steroids etc . Conclusion: The Aqueous Garlic Extract (AGE) displayed potent anti- B. anthracis activity. It was better than that displayed by Azadirachta indica A. Juss. (Neem) and Mangifera indica L. while Curcuma longa L. (Turmeric) did not show any activity under the assay conditions used. Further work should be undertaken to explore the possible application of AGE in preventing anthrax incidences in endemic areas. Abstract Figure: