Agathisflavone for COVID-19

Abstract Coronaviruses constitute a significant threat to the human population. Severe acute respiratory syndrome coronavirus-2, SARS-CoV-2, is a highly pathogenic human coronavirus that has caused the coronavirus disease 2019 (COVID-19) pandemic. It has led to a global viral outbreak with an exceptional spread and a high death toll, highlighting the need for effective antiviral strategies. 3-Chymotrypsin-like protease (3CLpro), the main protease in SARS-CoV-2, plays an indispensable role in the SARS-CoV-2 viral life cycle by cleaving the viral polyprotein to produce 11 individual non-structural proteins necessary for viral replication. 3CLpro is one of two proteases that function to produce new viral particles. It is a highly conserved cysteine protease with identical structural folds in all known human coronaviruses. Inhibitors binding with high affinity to 3CLpro will prevent the cleavage of viral polyproteins, thus impeding viral replication. Multiple strategies have been implemented to screen for inhibitors against 3CLpro, including peptide-like and small molecule inhibitors that covalently and non-covalently bind the active site, respectively. In addition, allosteric sites of 3CLpro have been identified to screen for small molecules that could make non-competitive inhibitors of 3CLpro. In essence, this review serves as a comprehensive guide to understanding the structural intricacies and functional dynamics of 3CLpro, emphasizing key findings that elucidate its role as the main protease of SARS-CoV-2. Notably, the review is a critical resource in recognizing the advancements in identifying and developing 3CLpro inhibitors as effective antiviral strategies against COVID-19, some of which are already approved for clinical use in COVID-19 patients.

SARS-CoV-2 (severe acute respiratory distress syndrome coronavirus 2) is the causative agent for the novel coronavirus disease 2019 (COVID-19). It raises serious biosecurity questions due to its high contagious potential, thereby triggering rapid and efficient responses by the scientific community to take necessary actions against viral infections. Cumulative scientific evidence suggests that natural products remain one of the main sources for pharmaceutical consumption. It is due to their wide chemical diversity that they are able to fight against almost all kinds of diseases and disorders in humans and other animals. Knowing the overall facts, this study was carried out to investigate the chemical interactions between the active constituents of a promising medicinal plant, Myracrodruon urundeuva, and some specific proteins of SARS-CoV-2. For this, we used molecular docking to predict the most appropriate orientation by binding a molecule (a ligand) to its receptor (a protein). The best results were evaluated by screening their pharmacokinetic properties using the online tool pkCSM. Findings suggest that among 44 chemical compounds of M. urundeuva, agathisflavone, which is abundantly present in its leaf, exhibited excellent molecular affinity (−9.3 to −9.7 kcal.mol−1) with three functional proteins, namely, Spike, MPro, and RBD of SARS-CoV-2. In conclusion, M. urundeuva might be a good source of antiviral agents. Further studies are required to elucidate the exact mechanism of action of the bioactive compounds of M. urundeuva acting against SARS-CoV-2.