Inhibitory potentials of ivermectin, nafamostat, and camostat on spike protein and some nonstructural proteins of SARS-CoV-2: Virtual screening approach
et al., Jurnal Teknologi Laboratorium, doi:10.29238/teknolabjournal.v11i1.344 , Jun 2022
Ivermectin for COVID-19
4th treatment shown to reduce risk in
August 2020, now with p < 0.00000000001 from 106 studies, recognized in 24 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
In silico study of ivermectin, camostat, and nafamostat, showing that ivermectin had the best inhibitory action on the SARS-CoV-2 spike protein and Nsp10, while nafamostat had the best results for the other non-structural proteins. Authors note that the combination of ivermectin and nafamostat may be beneficial for COVID-19.
74 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N771, Dengue37,72,73 , HIV-173, Simian virus 4074, Zika37,75,76 , West Nile76, Yellow Fever77,78, Japanese encephalitis77, Chikungunya78, Semliki Forest virus78, Human papillomavirus57, Epstein-Barr57, BK Polyomavirus79, and Sindbis virus78.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins71,73,74,80 , shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing38, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination41,81, shows dose-dependent inhibition of wildtype and omicron variants36, exhibits dose-dependent inhibition of lung injury61,66, may inhibit SARS-CoV-2 via IMPase inhibition37, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation9, inhibits SARS-CoV-2 3CLpro54, may inhibit SARS-CoV-2 RdRp activity28, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages60, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation82, may interfere with SARS-CoV-2's immune evasion via ORF8 binding4, may inhibit SARS-CoV-2 by disrupting CD147 interaction83-86, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1959,87, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage8, may minimize SARS-CoV-2 induced cardiac damage40,48, may counter immune evasion by inhibiting NSP15-TBK1/KPNA1 interaction and restoring IRF3 activation88, may disrupt SARS-CoV-2 N and ORF6 protein nuclear transport and their suppression of host interferon responses1, reduces TAZ/YAP nuclear import, relieving SARS-CoV-2-driven suppression of IRF3 and NF-κB antiviral pathways35, increases Bifidobacteria which play a key role in the immune system89, has immunomodulatory51 and anti-inflammatory70,90 properties, and has an extensive and very positive safety profile91.
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12.
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Umar et al., 30 Jun 2022, peer-reviewed, 6 authors.
In silico studies are an important part of preclinical research, however results may be very different in vivo.
JURNAL TEKNOLOGI LABORATORIUM
doi:10.29238/teknolabjournal.v11i1.344
The search for potential oral drugs either through synthetic routes or by drug repurposing for combating the dreaded covid-19 virus is still ongoing. The coronavirus spike glycoprotein and several other non-structural proteins play crucial roles in the replication and transmission of this virus. Recent research have identified ivermectin, nafamostat, and camostat as promising drug inhibitors of SARS-CoV-2 target proteins. The broad-spectrum inhibitory action of ivermectin, nafamostat, and camostat on the spike glycoprotein and some non-structural proteins of this virus was studied in silico. The spike glycoprotein, nsp3, nsp5, nsp9, nsp10, nsp13, and nsp16 were selected for this study and were
AUTHORS' CONTRIBUTIONS CED: Conceptualization, Data curation, Supervision, Methodology, Software HIU: Conceptualization, Supervision, Methodology, Data curation, Software. IAD: Visualization, Investigation. UEE: Visualization, Investigation. LCN: Original draft preparation, Writing-Reviewing and Editing. CEE: Original draft preparation, Writing-Reviewing and Editing.
FUNDING INFORMATION No funds, grants, or other support was received.
DATA AVAILABILITY STATEMENT All data generated or analyzed during this study are included in this published article.
DISCLOSURE STATEMENT The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency of the authors. The data is the result of the author's research and has never been published in other journals. The authors declare that they have no competing interests.
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