In Silico Study of Two Linear Furanocoumarins for Dual Inhibition of Human Rhinovirus and SARS-CoV-2

Abstract

In the discovery of antiviral drugs, targeting the 3-chymotrypsin-like cysteine protease (3CLpro) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is advantageous for developing a broad-spectrum antiviral agent for the treatment of coronaviruses and other respiratory viruses, such as rhinoviruses. The promising biological activities of linear furanocoumarins reported in the literature, in addition to their quantum electronic properties, led to the in silico study of these compounds. Analysis of chemical reactivity descriptors of 3-methoxypsoralen (1) and 3,5-dimethoxypsoralen (2) using DFT and ab initio Hartree–Fock (HF) methods indicates that the compounds are more water-soluble, which is a favorable characteristic for clinical applications. Vibrational spectroscopy data are also presented. Molecular docking results revealed that 1 and 2 strongly bind to 3CLpro with relative affinities of −5.5 and −5.6 kcal mol⁻¹, respectively. They were also docked against the human rhinovirus HRV3C main protease, with relative affinities of −8.4 and −7.3 kcal mol⁻¹, respectively.