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Biology subjects

Haddadi, K.

Publications and source records attributed to Haddadi, K..

3 recordsLinked to original sources

Breaking Through Microbial Defences - Organic Acid-Based Deep Eutectic Solvents as a Neoteric Strategy in Bacterial Biofilm, Persister, and Fungal Control

This study explores the adaptation of organic acid-based deep eutectic solvents (OA-DESs) as effective antimicrobial agents. Having already demonstrated their efficacy against planktonic bacteria in our previous research, we now investigate their impact on more complex microbial forms, including biofilms, persister cells, and fungi (both human pathogenic and phytopathogenic). Our experiments revealed that OA-DESs effectively eradicated MRSA and Escherichia coli biofilms, inducing significant morphological changes. Notably, a three-log-unit reduction was observed for most OA-DESs at concentrations below 1% v/v, a remarkable achievement for this class of materials. Additionally, with only one exception, OA-DESs did not promote persister cell formation, underscoring their potential for complete biofilm eradication. In another part of our study, OA-DESs were compared to conventional DESs against Candida albicans, Candida auris, and Aspergillus fumigatus. Results showed that while individual DES components exhibited minimal activity, their combination effectively inhibited fungal growth and induced substantial morphological changes. Lastly, OA-DESs were tested against the phytopathogens Zymoseptoria tritici and Venturia inaequalis. Though their activity was less pronounced compared to pathogenic strains, most OA-DESs inhibited the growth of both fungi at the highest tested concentrations. Despite the broad scope of this study, we believe this study provides valuable insights into the potential of DESs as antimicrobial agents, offering a strong foundation for future research and innovation in this field.

microbiology↗

SARS-CoV-2 receptor binding mutations and antibody mediated immunity.

SARS-CoV-2 mutations can impact infectivity, viral load, and overall morbidity/mortality during infection. In this analysis, we look at the mutational landscape of the SARS-CoV-2 receptor binding domain, a structure that is antigenic and allows for viral binding to the host. We analyze 104193 GISAID sequences acquired on October 15th, 2020 with a majority of sequences (96%) containing point mutations. We report high frequency mutations with improved binding affinity to ACE2 including S477N, N439K, V367F, and N501Y and address the potential impact of RBD mutations on antibody binding. The high frequency S477N mutation is present in 6.7% of all SARS-CoV-2 sequences, co-occurs with D614G, and is currently present in 14 countries. To address RBD-antibody interactions we take a subset of human derived antibodies and define their interacting residues using PDBsum. Our analysis shows that adaptive immunity against SARS-CoV-2 enlists broad coverage of the RBD suggesting that antibody mediated immunity should be sufficient to resolve infection in the presence of RBD point mutations that conserve structure.

bioinformatics↗

Database for drug metabolism and comparisons, NICEdrug.ch, aids discovery and design

The discovery of a drug requires over a decade of enormous research and financial investments--and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch database, which incorporates 250,000 bio-active molecules, and studied their metabolic targets, fate, and toxicity. NICEdrug.ch includes a unique fingerprint that identifies reactive similarities between drug-drug and drug-metabolite pairs. We use NICEdrug.ch to evaluate inhibition and toxicity by the anticancer drug 5-fluorouracil, and suggest avenues to alleviate its side effects. Clustering based on this fingerprint in statins identified drugs for repurposing. We propose shikimate 3-phosphate for targeting liver-stage malaria with minimal impact on the human host cell. Finally, NICEdrug.ch suggests over 1,300 drugs and food molecules to target COVID-19 and explains their inhibitory mechanisms. The NICEdrug.ch database is accessible online to systematically identify the reactivity of small molecules and druggable enzymes with practical applications in lead discovery and drug repurposing.

pharmacology and toxicology↗