Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target

Öz Currently, the world suffers from a new coronavirus SARS-CoV-2 that causes COVID-19. Therefore, there is a need for the urgent development of novel drugs and vaccines for COVID-19. Since it can take years to develop new drugs against this disease, here we used a hybrid combined molecular modeling approach in virtual drug screening repurposing study to identify new compounds against this disease. One of the important SARS-CoV-2 targets namely type 2 transmembrane serine protease (TMPRSS2) was screened with NPC’s NIH small molecule library which includes approved drugs by FDA and compounds in clinical investigation. We used 6654 small molecules in molecular docking and top-50 docking scored compounds were initially used in short (10-ns) molecular dynamics (MD) simulations. Based on average MM/GBSA binding free energy results, long (100-ns) MD simulations were employed for the identified hits. Both binding energy results as well as crucial residues in ligand binding were also compared with a positive control TMPRSS2 inhibitor, Camostat mesylate. Based on these numerical calculations we proposed a compound (benzquercin) as strong TMPRSS2 inhibitor. If these results can be validated by in vitro and in vivo studies, benzquercin can be considered to be used as inhibitor of TMPRSS2 at the clinical studies.

Kaynakça

Blanco-Melo D, 2020, CELL, V181, P1036, DOI 10.1016/j.cell.2020.04.026

Cao YN, 2020, CELL DISCOV, V6, DOI 10.1038/s41421-020-0147-1

Durdagi S., 2020, SCREENING CLIN APPRO, DOI [10.26434/chemrxiv.12032712.v2., DOI 10.26434/CHEMRXIV.12032712.V2]

Durdagi S, 2018, EUR J MED CHEM, V145, P273, DOI 10.1016/j.ejmech.2017.12.021

EVANS DJ, 1985, J CHEM PHYS, V83, P4069, DOI 10.1063/1.449071

Hoffmann M, 2020, CELL, V181, P271, DOI 10.1016/j.cell.2020.02.052

Is YS, 2018, ACS CHEM NEUROSCI, V9, P1768, DOI 10.1021/acschemneuro.8b00095

MARTYNA GJ, 1994, J CHEM PHYS, V101, P4177, DOI 10.1063/1.467468

McKee DL, 2020, PHARMACOL RES, V157, DOI 10.1016/j.phrs.2020.104859

Mousavizadeh L, 2021, J MICROBIOL IMMUNOL, V54, P159, DOI [10.1016/j.jmii.2020.03.022BY-, 10.1016/j.jmii.2020.03.022]

Sanders JM, 2020, PHARM TREATMENTS COR, DOI [10.1001/jama.2020.6019, DOI 10.1001/JAMA.2020.6019]

Shoichet BK, 2002, CURR OPIN CHEM BIOL, V6, P439, DOI 10.1016/S1367-5931(02)00339-3

Tutumlu G, 2020, FRONT CHEM, V8, DOI 10.3389/fchem.2020.00167

Zhang R, 2020, LIFE SCI, V250, DOI 10.1016/j.lfs.2020.117583

Kaynak Göster

Bibtex @araştırma makalesi { tbtkbiology943538, journal = {Turkish Journal of Biology}, issn = {1300-0152}, eissn = {1303-6092}, address = {}, publisher = {TÜBİTAK}, year = {2020}, volume = {44}, pages = {185 - 191}, doi = {}, title = {Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target}, key = {cite}, author = {Durdagi, Serdar} }
APA Durdagi, S . (2020). Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target . Turkish Journal of Biology , Special Issue on COVID-19 , 185-191 . Retrieved from https://dergipark.org.tr/tr/pub/tbtkbiology/issue/62502/943538
MLA Durdagi, S . "Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target" . Turkish Journal of Biology 44 (2020 ): 185-191 <https://dergipark.org.tr/tr/pub/tbtkbiology/issue/62502/943538>
Chicago Durdagi, S . "Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target". Turkish Journal of Biology 44 (2020 ): 185-191
RIS TY - JOUR T1 - Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target AU - Serdar Durdagi Y1 - 2020 PY - 2020 N1 - DO - T2 - Turkish Journal of Biology JF - Journal JO - JOR SP - 185 EP - 191 VL - 44 IS - SI-1 SN - 1300-0152-1303-6092 M3 - UR - Y2 - 2020 ER -
EndNote %0 Turkish Journal of Biology Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target %A Serdar Durdagi %T Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target %D 2020 %J Turkish Journal of Biology %P 1300-0152-1303-6092 %V 44 %N SI-1 %R %U
ISNAD Durdagi, Serdar . "Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target". Turkish Journal of Biology 44 / SI-1 (Haziran 2020): 185-191 .
AMA Durdagi S . Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target. Turkish Journal of Biology. 2020; 44(SI-1): 185-191.
Vancouver Durdagi S . Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target. Turkish Journal of Biology. 2020; 44(SI-1): 185-191.
IEEE S. Durdagi , "Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target", Turkish Journal of Biology, c. 44, sayı. SI-1, ss. 185-191, Haz. 2020

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