4'-hydroxyisolonchocarpin for COVID-19

Computer-aided drug design by molecular docking, statistical analysis like multiple linear regression (MLR), principal component analysis (PCA), and molecular dynamics studies can emerge as an efficient approach to designing promising core scaffolds for coronavirus medication. The main protease [3-chymotrypsin-like protease (3CLpro)] of severe acute respiratory syndrome coronavirus (SARS-CoV)-1 and SARS-CoV-2 is one of the critical targets for designing and developing broad-spectrum antiviral therapeutic drugs. The main objective of this study was to investigate potential phytochemicals against SARS-CoV-1 and SARS-CoV-2 to ensure effective natural product-induced therapy. In this evaluation, we have selected 40 reported phytochemicals to design efficient core scaffolds that can act as potent inhibitors against the main proteases of SARS-CoV-2 and SARS-CoV-1. We categorized the selected phytochemicals into a more bioavailable and less bioavailable set, considering phytochemical drug likeliness properties. All the selected phytochemicals vigorously interacted with the catalytic dyads His41 and Cys145. Statistical analysis by MLR confirmed their contribution to structural features on binding affinities and PCA analysis for structural activity relationships for their structural pattern recognition to determine the core scaffold inhibitors. We confirmed that 4′-Hydroxyisolonchocarpin and BrussochalconeA were safe and exhibited excellent pharmacological properties. Because 4′-Hydroxyisolonchocarpin and BrussochalconeA are flavonoid derivatives, they exhibit the chalcone’s ring. The presence of the reactive α,β-unsaturated system in the chalcone’s rings showed different potential pharmacokinetics with an insignificant toxicological profile. Our comprehensive computational and statistical analysis reveals that these selected phytochemicals (4′-Hydroxyisolonchocarpin, BrussochalconeA) can be used to design potential broad antiviral inhibitors against SARS-CoV-2 and SARS-CoV-1.

The recent pandemic of COVID-19 caused by the SARS-CoV-2 virus has brought upon the world an unprecedented challenge. During its acute dissemination, a rush for vaccines started, making the scientific community come together and contribute to the development of efficient therapeutic agents and vaccines. Natural products have been used as sources of individual molecules and extracts capable of inhibiting/neutralizing several microorganisms, including viruses. Natural extracts have shown effective results against the coronavirus family, when first tested in the outbreak of SARS-CoV-1, back in 2002. In this review, the relationship between natural extracts and SARS-CoV is discussed, while also providing insight into misinformation regarding the use of plants as possible therapeutic agents. Studies with plant extracts on coronaviruses are presented, as well as the main inhibition assays and trends for the future regarding the yet unknown long-lasting effects post-infection with SARS-CoV-2.