Identifying potent inhibitory phytocompounds from Lagerstroemia speciosa against SARS-Coronavirus-2: structure-based virtual screening.

The ongoing spillover of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) calls for expedited countermeasure through developing therapeutics from natural reservoirs and/or the use of less time-consuming drug discovery methodologies. This study aims to apply these approaches to identify potential blockers of the virus from the longstanding medicinal herb, Lagerstroemia speciosa, through comprehensive computational-based screening. Nineteen out of 22 L. speciosa phytochemicals were selected on the basis of their pharmacokinetic properties. SARS-CoV-2 Main protease (Mpro), RNA-directed RNA polymerase (RdRp), Envelope viroporin protein (Evp) and receptor-binding domain of Spike glycoprotein (S-RBD), as well as the human receptor Angiotensin-converting enzyme-2 (hACE2) were chosen as targets. The screening was performed by molecular docking, followed by 100-ns molecular dynamic simulations and free energy calculations. 24-Methylene cycloartanol acetate (24MCA) was found as the best inhibitor for both Evp and RdRp, and sitosterol acetate (SA) as the best hit for Mpro, S-RBD and hACE2. Dynamic simulations, binding mode analyses, free energy terms and share of key amino acids in protein-drug interactions confirmed the stable binding of these phytocompounds to the hotspot sites on the target proteins. With their possible multi-targeting capability, the introduced phytoligands might offer promising lead compounds for persistent fight with the rapidly evolving coronavirus. Therefore, experimental verification of their safety and efficacy is recommended.

Characterization of host receptor interaction with envelop protein of Kyasanur forest disease virus and predicting suitable epitopes for vaccine candidate.

Kyasanur forest disease (KFD) is a zoonotic disease that is endemic to southern India and caused by KFD virus (KFDV) belonging to the family Flaviviridae. Humans are the dead-end host of the KFDV life cycle. The absence of effective treatment strategies against KFD can be attributed to a lack of studies on the mechanistic part of the spread of the disease. Hypothesizing molecular etiological similarity of KFDV to other well characterized flaviviruses, such as dengue virus (DENV), we focused on predicting the target receptor protein(s) in host and provided molecular basis of receptor-mediated recognition of the human host by KFDV envelop protein (EKFDV), drawing from the extant knowledge on the dengue counterpart, EDENV. Indeed, in silico approach helped to identify that the EKFDV structure closely resembles the EDENV structure and indicated DC-SIGN and/or Mannose receptors to be the plausible target host receptors. Immune-informatics approach aided in predicting 10 epitopes from E, NS1, NS2A, and NS2B proteins of the KFDV-P9605 genotype for vaccine design against KFDV. Further, molecular dynamics simulation (MDS) analyses of their complexes with human leukocyte antigens (HLAs) identified the epitopes DISLTCRVT and YAMEIRPVH as two high ranking candidates for vaccine design.Communicated by Ramaswamy H. Sarma.