<em>IN SILICO </em>EVALUATION OF H1-ANTIHISTAMINE DRUGS AS POTENTIAL INHIBITORS OF SARS-COV-2 RNA-DEPENDENT RNA POLYMERASE: A REPURPOSING STUDY FOR COVID-19 THERAPY
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IN SILICO EVALUATION OF H1-ANTIHISTAMINE DRUGS AS POTENTIAL INHIBITORS OF SARS-COV-2 RNA-DEPENDENT RNA POLYMERASE: A REPURPOSING STUDY FOR COVID-19 THERAPY

Turk J Pharm Sci 0;0(0):undefined-undefined
1. Department of Pharmaceutical Chemistry Institute of Health Sciences, Marmara University, İstanbul, Turkey
2. Department of Pharmaceutical Chemistry Faculty of Pharmacy, Marmara University, Istanbul, Turkey
3. Department of Pharmaceutical Chemistry Faculty of Pharmacy, Fenerbahçe University, İstanbul, Turkey
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Abstract

INTRODUCTION

SARS-CoV-2, from the Coronaviridae family, is the seventh known type of coronavirus to infect humans and causes acute respiratory syndrome. Rapidly spreading worldwide, the virus emerged in Wuhan, China, in December 2019, leading to an ongoing pandemic with more than 775 million confirmed cases and over 7 million deaths (as of May 5th 2024), according to World Health Organization data. Although vaccination efforts have been undertaken, the lack of an FDA-approved antiviral agent aimed at curing the disease has made the drug repurposing a key approach for urgent intervention in the COVID-19 pandemic. This study investigates the potential of H1-antihistamines as antiviral agents against SARS-CoV-2, the virus that causes COVID-19. We targeted the main replicase/transcriptase complex (RTC) of the virus, specifically nonstructural protein 12 (nsp12), which is essential for viral RNA synthesis.

METHODS

Using molecular docking techniques, we explored the interactions between H1-antihistamines and RNA-dependent RNA polymerase (RdRp), a key enzyme in viral replication. The three-dimensional structure of 37 H1-antihistamine molecules was drawn and their energies were minimized using Spartan 0.4. Subsequently, we conducted a docking study with Autodock Vina to assess the binding affinity of these molecules to the target site. The docking scores and conformations were then visualized using Discovery Studio.

RESULTS

The results examined showed that the docking scores of the H1-antihistamines were between -5.0 and -8.3 kcal/mol. The findings suggest that among all analyzed drugs, bilastine, fexofenadine, montelukast, zafirlukast, mizolastine, rupatadine can bind with the best binding energy (< -7.0 kcal/mol) and inhibit RdRp, potentially halting the replication of the virus.

DISCUSSION AND CONCLUSION

This study highlights the promise of H1-antihistamines in combating COVID-19 and underscores the value of computational approaches in rapid drug discovery and repurposing efforts. Finally, experimental studies are required to measure the potency of H1-antihistamines before their clinical use against COVID-19 as RdRp inhibitors.

Keywords: SARS-CoV-2; RNA-dependent RNA polymerase; molecular docking; H1-antihistamines; drug repurposing

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