Version 1
: Received: 25 February 2020 / Approved: 28 February 2020 / Online: 28 February 2020 (02:38:05 CET)
Version 2
: Received: 8 March 2020 / Approved: 9 March 2020 / Online: 9 March 2020 (02:29:04 CET)
Sekhar Talluri, “Molecular Docking and Virtual Screening based prediction of drugs for COVID-19”, Combinatorial Chemistry & High Throughput Screening (2020) 23: 1. https://doi.org/10.2174/1386207323666200814132149
Sekhar Talluri, “Molecular Docking and Virtual Screening based prediction of drugs for COVID-19”, Combinatorial Chemistry & High Throughput Screening (2020) 23: 1. https://doi.org/10.2174/1386207323666200814132149
Sekhar Talluri, “Molecular Docking and Virtual Screening based prediction of drugs for COVID-19”, Combinatorial Chemistry & High Throughput Screening (2020) 23: 1. https://doi.org/10.2174/1386207323666200814132149
Sekhar Talluri, “Molecular Docking and Virtual Screening based prediction of drugs for COVID-19”, Combinatorial Chemistry & High Throughput Screening (2020) 23: 1. https://doi.org/10.2174/1386207323666200814132149
Abstract
SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19, based on predicted binding energy to the target Mpro of SARS-CoV-2, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.
Keywords
virtual screening; molecular docking; drug repurposing; drug repositioning; anti-viral drugs; Coronavirus; COVID-19; 2019-nCoV; SARS-CoV-2
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:
9 March 2020
Commenter:
Sekhar Talluri
Commenter's Conflict of Interests:
Author
Comment:
Minor changes to the title and Abstract.
Explain potential off-target effects for drugs in clinical trials for COVID-19, based on predicted binding energy.
Minor changes to introduction, results and discussion.
Reformatting of references.
(Click to see Publons profile: )
Commenter's Conflict of Interests:
I am Author of this manuscript.
Comment:
In Table 3, regarding drugs in clinical trials, I did not mention "abidol hydrochoride," which is one of the drugs listed in clinical trial NCT04255017. I had assumed that it was same as "arbidol" based on the title of the study which indicated that it was an antiviral: "An Open, Prospective, Randomized Controlled Cohort Study to Compare the Efficacy of Three Antiviral Drugs(Abidol Hydrochloride, Oseltamivir and Lopinavir/Ritonavir) in the Treatment of 2019-nCoV Pneumonia."
Arbidol which is also used in another clinical trial is an antiviral as per the reference in drugbank: "Haviernik J, Stefanik M, Fojtikova M, Kali S, Tordo N, Rudolf I, Hubalek Z, Eyer L, Ruzek D: Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses. Viruses. 2018 Apr 10;10(4). pii: v10040184. doi: 10.3390/v10040184. [PubMed:29642580] " -- (Umifenovir is included in Table 3)
I was unable to find a reference for Abidol in Drugbank. But, based on a google search it is a trade name for tramadol which is an opiod analgesic and SNRI (according to Drugbank).
I will try to contact the authors of the clinical trial to resolve this issue. If abidol was used in the clinical trial, then I will discuss it in my next revision of the manuscript.
Commenter: Sekhar Talluri
Commenter's Conflict of Interests: Author
Explain potential off-target effects for drugs in clinical trials for COVID-19, based on predicted binding energy.
Minor changes to introduction, results and discussion.
Reformatting of references.
Commenter:
Commenter's Conflict of Interests: I am Author of this manuscript.
Arbidol which is also used in another clinical trial is an antiviral as per the reference in drugbank: "Haviernik J, Stefanik M, Fojtikova M, Kali S, Tordo N, Rudolf I, Hubalek Z, Eyer L, Ruzek D: Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses. Viruses. 2018 Apr 10;10(4). pii: v10040184. doi: 10.3390/v10040184. [PubMed:29642580] " -- (Umifenovir is included in Table 3)
I was unable to find a reference for Abidol in Drugbank. But, based on a google search it is a trade name for tramadol which is an opiod analgesic and SNRI (according to Drugbank).
I will try to contact the authors of the clinical trial to resolve this issue. If abidol was used in the clinical trial, then I will discuss it in my next revision of the manuscript.