Design of ZnO-Drug Nanocarriers against the Main Protease of SARS-CoV-2 (COVID-19): An In Silico Assay

Erik Díaz-Cervantes,Faustino Aguilera-Granja,Cristal Zenteno-Zúñiga,Vicente Rodríguez-González

doi:10.3390/applnano2030018

Abstract

The treatment of coronavirus diseases (COVID-19) is a principal aim worldwide that is required restore public health in the population. To this end, we have been studied several kinds of de novo and repurposed drugs to investigate their ability to inhibit the replication of the virus which causes the current pandemic—the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, finding a vehicle that promotes the controlled dosage is vital for avoiding secondary effects. For this reason, the present work exposes a nanostructured carrier based on ZnO, which is coupled to three repurposed drugs (Chloroquine, Dipyridamole, and Lopinavir) to understand the chemical interaction of the formed composite. The designed composites are modeled and optimized using the DFT formalism. In obtaining exergonic adsorption energies, we found values between 0.582 to 2.084 eV, depending on the used drug. At the same time, the HOMO orbitals demonstrate the electronic overlap between the ZnO-Np and the Lopinavir, which is the molecule with the higher adsorption energy. Finally, we carried out a docking assay to investigate the interaction of free drugs and composites with the main protease of the SARS-CoV-2, finding that the coupling energy of the composites (at around to 0.03 eV) was higher, compared with the free drugs. As such, our results suggest a controlled dosage of the drug on the SARS-CoV-2 target.

Highlights

The current pandemic caused by the coronavirus disease (COVID-19) has affected the world population, causing more than four million deaths and infection in 185 million people worldwide [1]
In the present work we proposed the computational study of two single models of nanoparticles of ZnO interacting with three repurposed drugs—Chloroquine (Clq), dipyridamole (Dip), and lopinavir (Lop)—with the intention of finding the formation of these kinds of composites and their orbital interactions
The whole molecules were optimized through the Gaussian 09 (G09) package [25], using the formalism of the density functional theory (DFT) at the level of the hybrid functional M06L [26,27], using the basis set 6-31G(d,p) [28] and the pseudopotential LANL2DZ [29] for the Zn atoms

Summary

Introduction

The current pandemic caused by the coronavirus disease (COVID-19) has affected the world population, causing more than four million deaths and infection in 185 million people worldwide [1]. Regarding COVID-19, several research groups have been working to find a cure for this disease, considering both a de novo drug design [5,6] and the use of drug repurposing [7,8,9]. The molecular targets to these compounds play a vital role in the drug design, which have been reported mainly as one surface protein of the virus, a socalled spike [10], and as the main protease or 3C-like protease (SARS-CoV-2-MPro) [11,12,13,14]. Our research group has reported one non-protein protease inhibitor [17] which works to inhibit and stop the replication process of this novel virus

Methods

Discussion

Conclusion