Screening of Clinically Approved and Investigation Drugs as Potential Inhibitors of SARS-CoV-2: A Combined in silico and in vitro Study

Serdar Durdagi*, Muge Didem Orhan, Busecan Aksoydan, Seyma Calis, Berna Dogan, Kader Sahin, Aida Shahraki, Necla Birgül Iyison, Timucin Avsar*

*Bu çalışma için yazışmadan sorumlu yazar

Araştırma sonucu: ???type-name???Makalebilirkişi

8 Atıf (Scopus)

Özet

In the current study, we used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH's NPC database in our drug repurposing study. SARS-CoV-2 main protease as well as Spike protein/ACE2 targets were used in virtual screening and top-100 compounds from each docking simulations were considered initially in short molecular dynamics (MD) simulations and their average binding energies were calculated by MM/GBSA method. Promising hit compounds selected based on average MM/GBSA scores were then used in long MD simulations. Based on these numerical calculations following compounds were found as hit inhibitors for the SARS-CoV-2 main protease: Pinokalant, terlakiren, ritonavir, cefotiam, telinavir, rotigaptide, and cefpiramide. In addition, following 3 compounds were identified as inhibitors for Spike/ACE2: Denopamine, bometolol, and rotigaptide. In order to verify the predictions of in silico analyses, 4 compounds (ritonavir, rotigaptide, cefotiam, and cefpiramide) for the main protease and 2 compounds (rotigaptide and denopamine) for the Spike/ACE2 interactions were tested by in vitro experiments. While the concentration-dependent inhibition of the ritonavir, rotigaptide, and cefotiam was observed for the main protease; denopamine was effective at the inhibition of Spike/ACE2 binding.

Orijinal dilİngilizce
Makale numarası2100062
DergiMolecular Informatics
Hacim41
Basın numarası2
DOI'lar
Yayın durumuYayınlandı - Şub 2022
Harici olarak yayınlandıEvet

Bibliyografik not

Publisher Copyright:
© 2021 Wiley-VCH GmbH

Finansman

This study was funded by Scientific Research Projects Commission of Bahçeşehir University. Project number: BAU.BAP.2020.01. This study was also funded by the The Scientific and Technological Research Council of Turkey (TÜBİTAK), within the program number of 18AG003. The numerical calculations reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources). This study was funded by Scientific Research Projects Commission of Bahçeşehir University. Project number: BAU.BAP.2020.01. This study was also funded by the The Scientific and Technological Research Council of Turkey (TÜBİTAK), within the program number of 18AG003. The numerical calculations reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources).

FinansörlerFinansör numarası
Scientific Research Projects Commission of Bahçeşehir UniversityBAU.BAP.2020.01
TUBITAK ULAKBIM
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu18AG003

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