Version 1
: Received: 8 April 2020 / Approved: 9 April 2020 / Online: 9 April 2020 (14:59:37 CEST)
Version 2
: Received: 30 May 2020 / Approved: 1 June 2020 / Online: 1 June 2020 (02:42:54 CEST)
How to cite:
Strodel, B.; Olubiyi, O.; Olagunju, M.; Keutmann, M.; Loschwitz, J. High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2. Preprints2020, 2020040161. https://doi.org/10.20944/preprints202004.0161.v1
Strodel, B.; Olubiyi, O.; Olagunju, M.; Keutmann, M.; Loschwitz, J. High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2. Preprints 2020, 2020040161. https://doi.org/10.20944/preprints202004.0161.v1
Strodel, B.; Olubiyi, O.; Olagunju, M.; Keutmann, M.; Loschwitz, J. High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2. Preprints2020, 2020040161. https://doi.org/10.20944/preprints202004.0161.v1
APA Style
Strodel, B., Olubiyi, O., Olagunju, M., Keutmann, M., & Loschwitz, J. (2020). High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2. Preprints. https://doi.org/10.20944/preprints202004.0161.v1
Chicago/Turabian Style
Strodel, B., Monika Keutmann and Jennifer Loschwitz. 2020 "High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2" Preprints. https://doi.org/10.20944/preprints202004.0161.v1
Abstract
We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, Mpro of the COVID-19 virus. With the high-resolution X-ray crystallography structure of this viral enzyme recently being solved, CADD provides a veritable tool for rapidly screening diverse sets of compounds with the aim of identifying ligands capable of forming energetically favorable complexes with Mpro . From our screening of 1,082,653 compounds derived from the ZINC, the DrugBank, and our in-house African natural product libraries, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective Mpro inhibitors, which include FDA-approved drugs, drug candidates in clinical trials, as well as natural products. The top-ranking compounds are characterized by the presence of an extended ring system combined with functional groups that allow the ligands to adapt flexibly to the Mpro active site as, for example, present in the biflavonoid amentoflavone, one of the most promising compounds identified here. This particular chemical architecture leads to considerable stronger binding than found for reference compounds with in vitro demonstrated M pro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.
Keywords
COVID-19; SARS-CoV-2; main protease inhibition; virtual screening; drugs; natural products
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
3 May 2020
Commenter:
azhar salari
The commenter has declared there is no conflict of interests.
Comment:
Hi dear
Please tell me what is the name of the program you show the protein structure in your article?
You don't speak about this program in your article
Commenter: azhar salari
The commenter has declared there is no conflict of interests.
Please tell me what is the name of the program you show the protein structure in your article?
You don't speak about this program in your article