Blocking Effect of Natural Alkaloids on COVID-19 Pentameric Ion Channel: An in silico Perspective

Abstract

Numerous deaths worldwide have been caused by the coronavirus pandemic and are currently progressing with successive mutations and a lack of appropriate and definitive treatment. One of the drug targets to control the replication of the virus and treat this disease is to block the ion channel of the virus. This will lead to its death by disturbing the internal balance of the virus. Natural compounds such as alkaloids are usually known as effective compounds due to their medicinal characteristics and easy access to their sources. To this end, more than 3,200 natural alkaloid structures interacted with pentameric ion channels. Alkaloid compounds established significant and stable interactions with the channel. More clearly and in more detail, six alkaloid compounds with the best pharmacokinetics and binding affinity of less than -10.52 kcal/mol were selected as hit and suitable compounds for virus control. The compound of psammaplysin U (NA-1) with a binding affinity of -13.52 kcal/mol and binding free energy of -82.21 kcal/mol established hydrogen interactions with the amino acid of Val 25 in the B chain of the ion channel, which placed the compound at the top of the selected compounds. The molecular dynamics simulation of the ligand-protein complex in the 100 ps trajectory showed that the principal interactions were hydrogen and halogen bonding with the amino acids of Val 25 and Thr 30 in the B chain and A chain, respectively, which could be a suitable inhibitor to combat the COVID-19.