Elucidation on the Physicochemical Properties of Potential and Clinically Approved Antiviral Drugs: A Search for Effective Therapies against SARS-CoV-2 Infection

Abstract

COVID-19 has been confirmed in millions of individuals worldwide, rendering it a global medical emergency. In the absence of vaccines and the unavailability of effective drugs for the SARS-CoV-2 infection, vaccine development is being continuously explored and several antiviral compounds and immunotherapies are currently being investigated. Given the high similarity in genetic identity between SARS-CoV and SARS-CoV-2, the present investigation identified the interaction between the physicochemical properties and the antiviral activity of different potential and clinically approved antiviral drugs against SARS-CoV using hierarchically weighted principal component analysis. Representative drugs from the classes of neuraminidase inhibitors, reverse transcriptase inhibitors, protease inhibitors, nucleoside analogues, and other compounds with potential antiviral activity were examined. The pharmacologic classification and the biological activity of the different antiviral drugs were described using indices, namely, rotatable bond count, molecular weight, heavy atom count, and molecular complexity (92.32% contribution rate). The physicochemical properties and inhibitory action against SARS-CoV-2 of lopinavir, chloroquine, ivermectin, and ciclesonide validated the adequacy of the current computational approach. The findings of the present study provide additional information, although further investigation is warranted to identify potential targets and establish exact mechanisms, in the emergent search and design of antiviral drug candidates and their subsequent synthesis as effective therapies for COVID-19.

Keywords

• covid-19
• neuraminidase inhibitors
• nucleoside analogues
• principal component analysis
• protease inhibitors
• reverse transcriptase inhibitors