Papers by Kiandokht Hadadi
bioRxiv, 2021
SARS-CoV-2 mutations can impact infectivity, viral load, and overall morbidity/mortality during i... more 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 mediat...
Antibody Therapeutics
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations can impact infectivity, vi... more Severe acute respiratory syndrome coronavirus 2 (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 develop a bioinformatics platform and analyze 104 193 Global Initiative on Sharing All Influenza Data sequences acquired on 15 October 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 PDBsu...
eLife
The discovery of a drug requires over a decade of intensive research and financial investments – ... more The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied their enzymatic metabolic targets, fate, and toxicity. NICEdrug.ch includes a unique fingerprint that identifies reactive similarities between drug–drug and drug–metabolite pairs. We validated the application, scope, and performance of NICEdrug.ch over similar methods in the field on golden standard datasets describing drugs and metabolites sharing reactivity, drug toxicities, and drug targets. We use NICEdrug.ch to evaluate inhibition and toxicity by the anticancer drug 5-fluorouracil, and suggest avenues to alleviate its side effects. We propose shikimate 3-phosphate for targeting liver-stage malaria with minimal impact on the human host cell. Finally, NICEdrug.ch suggests over 1300 candidate drugs and food molecules to target C...
The discovery of a drug requires over a decade of enormous research and financial investments—and... more 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 ...
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Papers by Kiandokht Hadadi