tetano
Editor, Senior Moderator
Inform Med Unlocked
. 2021;26:100725.
doi: 10.1016/j.imu.2021.100725. Epub 2021 Sep 7.
Identification of novel transmembrane Protease Serine Type 2 drug candidates for COVID-19 using computational studies
Fatima A Elbadwi[SUP] 1 [/SUP], Elaf A Khairy[SUP] 1 [/SUP], Fatima O Alsamani[SUP] 1 [/SUP], Mariam A Mahadi[SUP] 1 [/SUP], Segood E Abdalrahman[SUP] 1 [/SUP], Zain Alsharf M Ahmed[SUP] 1 [/SUP], Inas Elsayed[SUP] 2 [/SUP], Walaa Ibraheem[SUP] 1 [/SUP], Abdulrahim A Alzain[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emergence has resulted in a global health crisis. As a consequence, discovering an effective therapy that saves lives and slows the spread of the pandemic is a global concern currently. In silico drug repurposing is highly regarded as a precise computational method for obtaining fast and reliable results. Transmembrane serine-type 2 (TMPRSS2) is a SARS CoV-2 enzyme that is essential for viral fusion with the host cell. Inhibition of TMPRSS2 may block or lessen the severity of SARS-CoV-2 infection. In this study, we aimed to perform an in silico drug repurposing to identify drugs that can effectively inhibit SARS-CoV-2 TMPRSS2. As there is no 3D structure of TMPRSS2 available, homology modeling was performed to build the 3D structure of human TMPRSS2. 3848 world-approved drugs were screened against the target. Based on docking scores and visual outcomes, the best-fit drugs were chosen. Molecular dynamics (MD) and density functional theory (DFT) studies were also conducted. Five potential drugs (Amikacin, isepamicin, butikacin, lividomycin, paromomycin) exhibited promising binding affinities. In conclusion, these findings empower purposing these agents.
Keywords: COVID-19; Docking; Drug repurposing; Homology modeling; Molecular dynamics; TMPRSS2.
. 2021;26:100725.
doi: 10.1016/j.imu.2021.100725. Epub 2021 Sep 7.
Identification of novel transmembrane Protease Serine Type 2 drug candidates for COVID-19 using computational studies
Fatima A Elbadwi[SUP] 1 [/SUP], Elaf A Khairy[SUP] 1 [/SUP], Fatima O Alsamani[SUP] 1 [/SUP], Mariam A Mahadi[SUP] 1 [/SUP], Segood E Abdalrahman[SUP] 1 [/SUP], Zain Alsharf M Ahmed[SUP] 1 [/SUP], Inas Elsayed[SUP] 2 [/SUP], Walaa Ibraheem[SUP] 1 [/SUP], Abdulrahim A Alzain[SUP] 1 [/SUP]
Affiliations
- PMID: 34514079
- PMCID: PMC8421083
- DOI: 10.1016/j.imu.2021.100725
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emergence has resulted in a global health crisis. As a consequence, discovering an effective therapy that saves lives and slows the spread of the pandemic is a global concern currently. In silico drug repurposing is highly regarded as a precise computational method for obtaining fast and reliable results. Transmembrane serine-type 2 (TMPRSS2) is a SARS CoV-2 enzyme that is essential for viral fusion with the host cell. Inhibition of TMPRSS2 may block or lessen the severity of SARS-CoV-2 infection. In this study, we aimed to perform an in silico drug repurposing to identify drugs that can effectively inhibit SARS-CoV-2 TMPRSS2. As there is no 3D structure of TMPRSS2 available, homology modeling was performed to build the 3D structure of human TMPRSS2. 3848 world-approved drugs were screened against the target. Based on docking scores and visual outcomes, the best-fit drugs were chosen. Molecular dynamics (MD) and density functional theory (DFT) studies were also conducted. Five potential drugs (Amikacin, isepamicin, butikacin, lividomycin, paromomycin) exhibited promising binding affinities. In conclusion, these findings empower purposing these agents.
Keywords: COVID-19; Docking; Drug repurposing; Homology modeling; Molecular dynamics; TMPRSS2.