Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2
Eweas et al.,
Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2,
Frontiers in Microbiology, doi:10.3389/fmicb.2020.592908
Molecular docking analysis showing that ivermectin efficiently binds to the viral S protein as well as the human cell surface receptors ACE-2 and TMPRSS2; therefore, it might be involved in inhibiting the entry of the virus into the host cell. It also binds to Mpro and PLpro of SARS-CoV-2; therefore, it might play a role in preventing the post-translational processing of viral polyproteins. The highly efficient binding of ivermectin to the viral N phosphoprotein and nsp14 is suggestive of its role in inhibiting viral replication and assembly.
Eweas et al., 25 Jan 2021, peer-reviewed, 3 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: ORIGINAL RESEARCH
published: 25 January 2021
doi: 10.3389/fmicb.2020.592908
Molecular Docking Reveals
Ivermectin and Remdesivir as
Potential Repurposed Drugs Against
SARS-CoV-2
Ahmad F. Eweas 1,2 , Amr A. Alhossary 3 and Ahmed S. Abdel-Moneim 4*
1
Department of Pharmaceutical and Medicinal Chemistry, National Research Centre, Cairo, Egypt, 2 Department of Science,
University of Technology and Applied Sciences Rustaq, Rustaq, Oman, 3 Rehabilitation Research Institute of Singapore,
Nanyang Technological University, Singapore, Singapore, 4 Microbiology Department, Virology Division, College of Medicine,
Taif University, Taif, Saudi Arabia
Edited by:
Michael Nevels,
University of St Andrews,
United Kingdom
Reviewed by:
Osmair Oliveira,
Federal Institute of São Paulo, Brazil
Shradha Khater,
Indian Institute of Technology
Bombay, India
*Correspondence:
Ahmed S. Abdel-Moneim
asa@tu.edu.sa;
asa@bsu.edu.eg
Specialty section:
This article was submitted to
Virology,
a section of the journal
Frontiers in Microbiology
Received: 21 August 2020
Accepted: 24 December 2020
Published: 25 January 2021
Citation:
Eweas AF, Alhossary AA and
Abdel-Moneim AS (2021) Molecular
Docking Reveals Ivermectin
and Remdesivir as Potential
Repurposed Drugs Against
SARS-CoV-2.
Front. Microbiol. 11:592908.
doi: 10.3389/fmicb.2020.592908
SARS-CoV-2 is a newly emerged coronavirus that causes a respiratory disease
with variable severity and fatal consequences. It was first reported in Wuhan and
subsequently caused a global pandemic. The viral spike protein binds with the ACE2 cell surface receptor for entry, while TMPRSS2 triggers its membrane fusion. In
addition, RNA dependent RNA polymerase (RdRp), 30 –50 exoribonuclease (nsp14),
viral proteases, N, and M proteins are important in different stages of viral replication.
Accordingly, they are attractive targets for different antiviral therapeutic agents.
Although many antiviral agents have been used in different clinical trials and included
in different treatment protocols, the mode of action against SARS-CoV-2 is still
not fully understood. Different potential repurposed drugs, including, chloroquine,
hydroxychloroquine, ivermectin, remdesivir, and favipiravir, were screened in the present
study. Molecular docking of these drugs with different SARS-CoV-2 target proteins,
including spike and membrane proteins, RdRp, nucleoproteins, viral proteases, and
nsp14, was performed. Moreover, the binding affinities of the human ACE-2 receptor
and TMPRSS2 to the different drugs were evaluated. Molecular dynamics simulation and
MM-PBSA calculation were also conducted. Ivermectin and remdesivir were found to
be the most promising drugs. Our results suggest that both these drugs utilize different
mechanisms at the entry and post-entry stages and could be considered potential
inhibitors of SARS-CoV-2 replication.
Keywords: antiviral, chloroquine/hydroxychloroquine, COVID-19, coronavirus disease, favipiravir, ivermectin,
remdesivir (GS-5734), SARS-CoV-2
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