Knowledgebase of potential multifaceted solutions to antimicrobial resistance.

Antimicrobial resistance (AMR), a top threat to global health, challenges preventive and treatment strategies of infections. AMR strains of microbial pathogens arise through multiple mechanisms. The underlying "antibiotic resistance genes" (ARGs) spread through various species by lateral gene transfer thereby causing global dissemination. Human methods also augment this process through inappropriate use, non-compliance to treatment schedule, and environmental waste. Worldwide significant efforts are being invested to discover novel therapeutic solutions for tackling resistant pathogens. Diverse therapeutic strategies have evolved over recent years. In this work we have developed a comprehensive knowledgebase by collecting alternative antimicrobial therapeutic strategies from literature data. Therapeutic strategies against bacteria, virus, fungus and parasites were extracted from PubMed literature using text mining. We have used a subjective (sentimental) approach for data mining new strategies, resulting in broad coverage of novel entities and subsequently add objective data like entity name (including IUPAC), potency, and safety information. The extracted data was organized in a freely accessible web platform, KOMBAT. The KOMBAT comprises 1104 Chemical compounds, 220 of newly identified antimicrobial peptides, 42 bacteriophages, 242 phytochemicals, 106 nanocomposites, and 94 novel entities for phototherapy. Entities tested and evaluated on AMR pathogens are included. We envision that this database will be useful for developing future therapeutics against AMR pathogens. The database can be accessed through http://kombat.igib.res.in/.

Phytovid19: a compilation of phytochemicals research in coronavirus.

The COVID-19 pandemic has immensely impacted global health causing colossal damage. The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased the quest to explore phytochemicals as treatment options. We summarize phytochemicals with activity against various coronaviruses including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). We compiled 705 phytochemical compounds through text mining of 893 PubMed articles. The physicochemical properties including molecular weight, lipophilicity, and the number of hydrogen bond donors and acceptors were determined from the structures of these compounds. A structure-based evaluation of these properties with respect to drug likeness showed that most compounds have a positive score of drug likeness. QSAR analysis showed that 5 descriptors, namely polar surface area, relative polar surface area, number of hydrogen bond donors, solubility, and lipophilicity, are significantly related to IC50. We envisage that these phytochemicals could be further explored for developing new potential therapeutic molecules for COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02035-6.

Computer-Aided Tools and Resources for Fungal Pathogens: An Application of Reverse Vaccinology for Mucormycosis.

Increasing fungal infections in immunocompromised hosts are a growing concern for global public health. Along with treatments, preventive measures are required. The emergence of reverse vaccinology has opened avenues for using genomic and proteomic data from pathogens in the design of vaccines. In this work, we present a comprehensive collection of various computational tools and databases with potential to aid in vaccine development. The ongoing pandemic has directed attention toward the increasing number of mucormycosis infections in COVID-19 patients. As a case study, we developed a computational pipeline for assisting vaccine development for mucormycosis. We obtained 6 proteins from 29,447 sequences from UniProtKB as potential vaccine candidates against mucormycosis, fulfilling multiple criteria. These criteria included potential characteristics, namely adhesin properties, surface or extracellular localization, antigenicity, no similarity to any human proteins, nonallergenicity, stability in vitro, and expression in fungal cells. These six proteins were predicted to have B cell and T cell epitopes, proinflammatory inducing peptides, and orthologs in several mucormycosis-causing species. These data could aid in vaccine development against mucormycosis for at-risk individuals.

Genetic Signatures in Ischemic Stroke: Focus on Aspirin Resistance.

BACKGROUND AND OBJECTIVE: Stroke is one of the leading causes of death. There has been compelling evidence that stroke has a genetic component. Genetic variants not only influence susceptibility to stroke but have also been found to alter the response to pharmacological agents and influence the clinical outcome of the disease. Stroke patients are treated with antiplatelet drugs like aspirin and clopidogrel to prevent a secondary stroke. In spite of the fact that many new antiplatelet drugs have been developed, aspirin is still considered as a golden standard for the antiplatelet therapy. Aspirin achieves its action by inhibiting platelet cyclooxygenase (COX) system involved in the formation of thromboxane A2 (TXA2). TXA2 triggers reactions leading to platelet activation and aggregation. This Non-steroidal anti-inflammatory drug (NSAID) acts by inhibiting this mediator. Despite the demonstrated benefits of aspirin, many patients develop secondary stroke or other vascular events, an observation that has led to the concept of aspirin resistance. Studies have demonstrated that adequate antiplatelet effects are not achieved in 5-45% patients suggesting that many individuals are aspirin resistant. Aspirin resistance is multifactorial in origin. A genetic component has also been suggested, and variants in more than a dozen genes involved in absorption, distribution, metabolism, excretion (ADME) and pharmacodynamics of aspirin have been shown to be responsible for aspirin resistance. In addition, the patients on aspirin treatment also face adverse drug reactions on account of genetic variation. CONCLUSION: The present review has been compiled with an aim to revisit all the studies related to genetic variation contributing to aspirin resistance as well as adverse drug reactions. The output of high throughput genomic technology like genome wide association studies and others has also been discussed.