New Concept of Small Molecules Interaction with Proteins – An Application to Potential COVID-19 Drugs

Irena Ćosić ,Drasko Cosic,Ivan F Lončarević

doi:10.18483/ijsci.2390

Abstract

With the huge demand for new effective drugs there is large need for computational methods capable of quick preselection of potential drugs before they are chemically and biologically tested. Particularly, with the latest outbreak of coronavirus SARS-CoV-2 causing COVID-19 pandemic, there is urgent need to preselect number of potential small molecule drugs that are already approved for other purposes and are clinically tested on infected people with variety of success. The already established Resonant Recognition Model (RRM) proposes that selectivity of biological interactions and functions between proteins, DNA/RNA, is based on resonant electromagnetic energy between interacting macromolecules at the specific frequency for the specific interaction/function. However, this approach cannot be applied for selective specific interactions between proteins and small molecules (potential drugs), as small molecules are not linear sequential molecules. Here, we extended the RRM model to small molecules interaction with proteins proposing that energy frequencies of free electrons in small molecules are the most relevant for their resonant recognition and interaction with proteins. This extended RRM model is firstly tested here with couple of natural examples to explain and support the model, following with application to already approved drugs, which are also potential COVID-19 drugs including remdesivir, chloroquine and hydroxychloroquine. This newly extended RRM model opens new avenues for biochemistry and pharmaceutical industry in analyzes of small molecule – protein interaction, and consequently in preselection of new drugs and drug design in general.

Highlights

With the huge developments within pharmaceutical industry towards finding the whole variety of effective drugs, there is large demand for pre-selective computational methods capable of quick preselection of small molecules before they are chemically and biologically tested
It is well known that small molecules selectively interact with proteins and we have extended the idea of Resonant Recognition Model (RRM) to small molecules proposing that such selective interactions between small molecules and proteins are based on resonant energy transfer
As there is overlap between characteristic RRM frequency fh for coronavirus spike proteins including SARS-CoV-2 and RRM frequency for hydroxychloroquine small molecules, we propose that hydroxychloroquine could interact with SARS-CoV-2 spike proteins and could be efficient in the first phase of infection by neutralising activity of spike proteins on the surface of coronavirus and preventing initial viral infection

Summary

Introduction

With the huge developments within pharmaceutical industry towards finding the whole variety of effective drugs (small molecules), there is large demand for pre-selective computational methods capable of quick preselection of small molecules before they are chemically and biologically tested Such quick preselection method would significantly narrow down number of potential molecular candidates that would need to be experimentally tested and would enormously save resources, time and costs involved in discovery of new drugs, and would provide quicker and better health outcomes. One of the quickest approaches is to test existing already approved and safe drugs for possibility of their activity against SARS-CoV-2 virus Along those lines, it has been quoted in reference [1]: ―Hydroxychloroquine and chloroquine have garnered unprecedented attention as potential therapeutic agents against COVID-19 following several small clinical trials, uncontrolled case series and public figure endorsement‖. In vitro and in vivo experimental data for the use of hydroxychloroquine and chloroquine against

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Results

Conclusion