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Evaluation of the potency of FDA-approved drugs on wild type and mutant SARS-CoV-2 helicase (Nsp13)

Ugurel et al., International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2020.09.138
Nov 2020  
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In Silico study reporting that folic acid, cangrelor, fludarabine, and polydatin are potential inhibitors of SARS-CoV-2 Nsp13.
13 preclinical studies support the efficacy of vitamin B9 for COVID-19:
Vitamin B9 has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function EFSA, Galmés, Galmés (B). Vitamin B9 inhibits SARS-CoV-2 In Silico Chen, Eskandari, Hosseini, Kumar, Moatasim, Pandya, Serseg, Ugurel, Zhang, reduces spike protein binding ability Zhang, binds with the spike protein receptor binding domain for alpha and omicron variants Pennisi, inhibits the SARS-CoV-2 nucleocapsid protein Chen, inhibits 3CLpro and PLpro in enzymatic assays Pennisi, significantly reduces infection for alpha and omicron SARS-CoV-2 pseudoviruses Pennisi, and inhibits ACE2 expression and SARS-CoV-2 infection in a mouse model Zhang.
Ugurel et al., 30 Nov 2020, peer-reviewed, 8 authors. Contact:,
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperVitamin B9All
Evaluation of the potency of FDA-approved drugs on wild type and mutant SARS-CoV-2 helicase (Nsp13)
Osman Mutluhan Ugurel, Ozal Mutlu, Emrah Sariyer, Sinem Kocer, Erennur Ugurel, Tugba Gul Inci, Oguz Ata, Dilek Turgut-Balik
International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2020.09.138
SARS-CoV-2 has caused COVID-19 outbreak with nearly 2 M infected people and over 100K death worldwide, until middle of April 2020. There is no confirmed drug for the treatment of COVID-19 yet. As the disease spread fast and threaten human life, repositioning of FDA approved drugs may provide fast options for treatment. In this aspect, structure-based drug design could be applied as a powerful approach in distinguishing the viral drug target regions from the host. Evaluation of variations in SARS-CoV-2 genome may ease finding specific drug targets in the viral genome. In this study, 3458 SARS-CoV-2 genome sequences isolated from all around the world were analyzed. Incidence of C17747T and A17858G mutations were observed to be much higher than others and they were on Nsp13, a vital enzyme of SARS-CoV-2. Effect of these mutations was evaluated on protein-drug interactions using in silico methods. The most potent drugs were found to interact with the key and neighbor residues of the active site responsible from ATP hydrolysis. As result, cangrelor, fludarabine, folic acid and polydatin were determined to be the most potent drugs which have potency to inhibit both the wild type and mutant SARS-CoV-2 helicase. Clinical data supporting these findings would be important towards overcoming COVID-19.
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