Inhibitory potentials of ivermectin, nafamostat, and camostat on spike protein and some nonstructural proteins of SARS-CoV-2: Virtual screening approach

Umar et al., Jurnal Teknologi Laboratorium, doi:10.29238/teknolabjournal.v11i1.344 , Jun 2022

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TMPRSS2 inhibitors

21st treatment shown to reduce risk in April 2021, now with p = 0.0007 from 29 studies.

Lower risk for mortality, ventilation, and recovery.

No treatment is 100% effective. Protocols combine treatments.

5,700+ studies for 169 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.

13 preclinical studies support the efficacy of TMPRSS2 inhibitors for COVID-19:

5 In Silico studies1-5

8 In Vitro studies2,4,6-11

Important missing comments or errors? Let us know.

Study covers TMPRSS2 inhibitors, ivermectin, nafamostat, and camostat.

1. Haque et al., Exploring potential therapeutic candidates against COVID-19: a molecular docking study, Discover Molecules, doi:10.1007/s44345-024-00005-5.springer.com, doi.org.

2. González-Paz et al., Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data, ACS Omega, doi:10.1021/acsomega.3c06968.acs.org, doi.org.

3. Umar et al., Inhibitory potentials of ivermectin, nafamostat, and camostat on spike protein and some nonstructural proteins of SARS-CoV-2: Virtual screening approach, Jurnal Teknologi Laboratorium, doi:10.29238/teknolabjournal.v11i1.344.teknolabjournal.com, doi.org.

4. Unal et al., Favipiravir, umifenovir and camostat mesylate: a comparative study against SARS-CoV-2, bioRxiv, doi:10.1101/2022.01.11.475889.biorxiv.org, doi.org.

5. Sgrignani et al., Computational Identification of a Putative Allosteric Binding Pocket in TMPRSS2, Frontiers in Molecular Biosciences, doi:10.3389/fmolb.2021.666626.frontiersin.org, doi.org.

6. Yathindranath et al., Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection, International Journal of Nanomedicine, doi:10.2147/IJN.S448005.dovepress.com, doi.org.

7. Martins et al., In Vitro Inhibition of SARS-CoV-2 Infection by Bromhexine hydrochloride, bioRxiv, doi:10.1101/2022.12.23.521817.biorxiv.org, doi.org.

8. Schultz et al., Pyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2, Nature, doi:10.1038/s41586-022-04482-x.nature.com, doi.org.

9. Hempel et al., Synergistic inhibition of SARS-CoV-2 cell entry by otamixaban and covalent protease inhibitors: pre-clinical assessment of pharmacological and molecular properties, Chemical Science, doi:10.1039/D1SC01494C.rsc.org, doi.org.

10. Carpinteiro et al., Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells, Journal of Biological Chemistry, doi:10.1016/j.jbc.2021.100701.jbc.org, doi.org.

11. Hoffman et al., SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell, doi:10.1016/j.cell.2020.02.052.cell.com, doi.org.

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.

This Paper TMPRSS2s All

JURNAL TEKNOLOGI LABORATORIUM

Haruna Isiyaku Umar, Ijeoma Akunna Duru, Uchechi Emmanuela Enenebeaku, Lynda Chioma Ngozi-Olehi, Christian Ebere Enyoh, Chidi Edbert Duru

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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