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

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 moleculeprotein interaction, and consequently in preselection of new drugs and drug design in general.

Analysis of UK and South African Strains of SARS-CoV-2 Using Resonant Recognition Model

“…When we have analysed spike S1 fragments from coronaviruses affecting humans, from UniProt database, using the RRM, the most prominent common RRM frequency has been found at f2=0.3145±0.0019, as presented in Figure 2 [14,23]. Figure 2.…”

“…The spike proteins, which are on the surface of coronavirus, are the first to approach and recognise host cells. Thus, we have analysed spike proteins from different coronaviruses with the aim to find out if there is any common component that can characterise spike's recognition and interaction with host cells [14]. When we have analysed spike proteins from different coronaviruses, from UniProt database, using the RRM, the most prominent common RRM frequency has been found at f1=0.2827±0.0009, as presented in Figure 1 [14].…”

“…Thus, we have analysed spike proteins from different coronaviruses with the aim to find out if there is any common component that can characterise spike's recognition and interaction with host cells [14]. When we have analysed spike proteins from different coronaviruses, from UniProt database, using the RRM, the most prominent common RRM frequency has been found at f1=0.2827±0.0009, as presented in Figure 1 [14]. It is interesting to note that there is one unique common characteristic frequency for all analysed spike proteins from many different coronaviruses.…”

“…The Resonant Recognition Model (RRM) is theoretical, biophysical model that can analyse interaction and recognition between proteins and their targets, which could be other proteins, DNA, RNA or small molecules, has been published previously in details [3][4][5][6][7][8][9][10][11][12][13][14]. The RRM model is based on the findings that certain periodicities (frequencies) within the distribution of energy of delocalised electrons along protein are critical for protein biological function and/or interaction with their targets.…”

“…For that purpose, we can use previously developed Resonant Recognition Model (RRM), which can computationally analyse and predict critical functional mutations within the protein, DNA/RNA [3][4][5][6][7][8][9][10][11][12][13][14]. The RRM model is based on findings that certain periodicities (frequencies) within the distribution of free electron energies along the protein, DNA/RNA are critical for macromolecular biological function/activity [3][4][5][6][7][8][9][10][11][12][13][14].…”