Screening of Clinically Approved and Investigation Drugs as Potential Inhibitors of SARS‐CoV‐2: A Combined in silico and in vitro Study. Issue 2 (16th September 2021)

• Record Type: Journal Article
• Authors: Durdagi, Serdar; Orhan, Muge Didem; Aksoydan, Busecan; Calis, Seyma; Dogan, Berna; Sahin, Kader; Shahraki, Aida; Iyison, Necla Birgül; Avsar, Timucin
• Is Part Of: Molecular informatics. Volume 41:Issue 2(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-16
• Subjects: COVID19 -- virtual screening -- drug repurposing -- SARS-CoV-2 -- main protease -- Spike/ACE-2 -- docking -- MD simulations; Cheminformatics -- Periodicals; QSAR (Biochemistry) -- Periodicals; Structure-activity relationships (Biochemistry) -- Periodicals; Drugs -- Structure-activity relationships -- Periodicals; 615.19
• DOI: 10.1002/minf.202100062
• Languages: English
• ISSNs: 1868-1743

Abstract

Abstract: 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. Abstract :