Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2: old drug with new implications
Qureshi et al.,
Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2: old drug with..,
Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1906750
In Silico study showing inhibition of importin-α1 by ivermectin, which disrupts SARS-CoV-2 replication.
Qureshi et al., 5 May 2021, peer-reviewed, 6 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Journal of Biomolecular Structure and Dynamics
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/tbsd20
Mechanistic insights into the inhibitory activity of
FDA approved ivermectin against SARS-CoV-2: old
drug with new implications
Urooj Qureshi, Sonia Mir, Sehrish Naz, Mohammad Nur-e-Alam, Sarfaraz
Ahmed & Zaheer Ul-Haq
To cite this article: Urooj Qureshi, Sonia Mir, Sehrish Naz, Mohammad Nur-e-Alam, Sarfaraz
Ahmed & Zaheer Ul-Haq (2021): Mechanistic insights into the inhibitory activity of FDA approved
ivermectin against SARS-CoV-2: old drug with new implications, Journal of Biomolecular Structure
and Dynamics, DOI: 10.1080/07391102.2021.1906750
To link to this article: https://doi.org/10.1080/07391102.2021.1906750
Published online: 05 May 2021.
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JOURNAL OF BIOMOLECULAR STRUCTURE AND DYNAMICS
https://doi.org/10.1080/07391102.2021.1906750
Mechanistic insights into the inhibitory activity of FDA approved ivermectin
against SARS-CoV-2: old drug with new implications
Urooj Qureshia#, Sonia Mira#, Sehrish Nazb, Mohammad Nur-e-Alamc, Sarfaraz Ahmedc and Zaheer Ul-Haqa,b
a
H.E.J. Research Institute of Chemistry, ICCBS, University of Karachi, Karachi, Pakistan; bDr. Panjwani Center for Molecular Medicine and
Drug Research, ICCBS, University of Karachi, Karachi, Pakistan; cDepartment of Pharmacognosy, King Saud University College of Pharmacy,
Riyadh, Kingdom of Saudi Arabia
Communicated by Ramaswamy H. Sarma
ABSTRACT
ARTICLE HISTORY
The novel corona virus (Covid-19) has become a great challenge worldwide since 2019, as no drug
has been reported yet. Different clinical trials are still under way. Among them is Ivermectin (IVM), an
FDA approved drug which was recently reported as a successful candidate to reduce SARS-CoV-2 viral
load by inhibiting Importin-a1 (IMP-a1) protein which subsequently affects nuclear transport of viral
proteins but its basic binding mode and inhibitory mechanism is unknown. Therefore, we aimed to
explore the inhibitory mechanism and binding mode of IVM with IMP-a1 via different computational
methods. Initially, comparative docking of IVM was performed against two different binding sites
(Nuclear Localization Signal (NLS) major and minor sites) of IMP-a1 to predict the probable binding
mode of IVM. Then, classical MD simulation was performed (IVM/NLS-Major site and IVM/NLS-Minor
site), to predict its comparative stability dynamics and probable inhibitory mechanism. The stability
dynamics and biophysical analysis of both sites highlighted the stable binding of IVM within NLSMinor site by establishing and maintaining more hydrophobic contacts with crucial residues, required
for IMP-a1 inhibition which were not observed in NLS-major site. Altogether, these results recommended the worth of IVM as a possible drug to limit the SARS-CoV-2 viral load and consequently
reduces its progression.
Received 21 September 2020
Accepted 17 March 2021
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