Yıl 2020, Cilt 7 , Sayı 3, Sayfalar 691 - 712 2020-10-30

In silico, 6LU7 protein inhibition using dihydroxy-3-phenyl coumarin derivatives for SARS-CoV-2

Mücahit ÖZDEMİR [1] , Baybars KÖKSOY [2] , Deniz CEYHAN [3] , Mustafa BULUT [4] , Bahattin YALCİN [5]

The new emerging coronavirus (SARS-CoV-2) has become a global health problem with very rapid transmission from person to person, causing severe acute respiratory problems. In the circumstance, the discovery of vaccines or drugs to eradicate or reduce the impact of the COVID-19 has made it imperative to develop new approaches. In the current situation, many drugs on the drug bank have been researched computationally and the synthesis has not been emphasized much. We tested 42 coumarin derivatives (1a-14c) containing 14 different substituents, which are secondary metabolites of plants, and the anticoagulant coumadin (warfarin) drug as a reference by docking method on 6LU7 main protease. Optimized geometries, electron motions and energy values of all coumarins were also determined using the Density Functional Theory (DFT) method. Coumarins formed strong interactions with HIS41, CYS145 and other amino acids in the active site of the main protease. In general, 6,7-dihydroxy-3-phenylcoumarin derivatives gave relatively higher scores, and for all coumarins, biphenyl (for 10a, -8.6 kcal/mol; 10b, -8.3 kcal/mol; 10c -7.9 kcal/mol) and 4-trifluoromethylphenyl (for 13a, -8.1 kcal/mol; 13b, -8.1 kcal/mol; 13c -8.3 kcal/mol) substituted coumarin had the highest score. The coumarins data reported in this study serves as a stepping stone for in vitro and in vivo experimental research for vaccine development purposes.
COVID-19 main protease, SARS-CoV-2, Molecular docking, Drug design, Coumarins
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Birincil Dil en
Konular Kimya, Organik, Biyokimya ve Moleküler Biyoloji
Yayınlanma Tarihi Summer
Bölüm Makaleler

Orcid: 0000-0002-0840-4953
Yazar: Mücahit ÖZDEMİR
Kurum: Marmara University
Ülke: Turkey

Orcid: 0000-0001-7939-5380
Yazar: Baybars KÖKSOY
Ülke: Turkey

Orcid: 0000-0003-1811-3858
Yazar: Deniz CEYHAN
Ülke: Turkey

Orcid: 0000-0001-9598-2649
Yazar: Mustafa BULUT
Kurum: Marmara University
Ülke: Turkey

Orcid: 0000-0003-4448-1101
Yazar: Bahattin YALCİN (Sorumlu Yazar)
Ülke: Turkey

Teşekkür The numerical calculations reported in this paper were fully performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources).

Başvuru Tarihi : 15 Haziran 2020
Kabul Tarihi : 9 Temmuz 2020
Yayımlanma Tarihi : 30 Ekim 2020

Vancouver Özdemir M , Köksoy B , Ceyhan D , Bulut M , Yalcin B . In silico, 6LU7 protein inhibition using dihydroxy-3-phenyl coumarin derivatives for SARS-CoV-2. Journal of the Turkish Chemical Society Section A: Chemistry. 2020; 7(3): 691-712.