Structure-based drug designing and immunoinformatics approach for SARS-CoV-2

Abstract

<jats:p>The prevalence of respiratory illness caused by the novel SARS-CoV-2 virus associated with multiple organ failures is spreading rapidly because of its contagious human-to-human transmission and inadequate globalhealth care systems. Pharmaceutical repurposing, an effective drug development technique using existing drugs, could shorten development time and reduce costs compared to those of de novo drug discovery. We carried out virtual screening of antiviral compounds targeting the spike glycoprotein (S), main protease (M<jats:sup>pro</jats:sup>), and the SARS-CoV-2 receptor binding domain (RBD)–angiotensin-converting enzyme 2 (ACE2) complex of SARS-CoV-2. PC786, an antiviral polymerase inhibitor, showed enhanced binding affinity to all the targets. Furthermore, the postfusion conformation of the trimeric S protein RBD with ACE2 revealed conformational changes associated with PC786 drug binding. Exploiting immunoinformatics to identify T cell and B cell epitopes could guide future experimental studies with a higher probability of discovering appropriate vaccine candidates with fewer experiments and higher reliability.</jats:p>

Conserved interactions required for in vitro inhibition of the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

“…The raging pandemic caused by SARS-CoV-2 requires a rapid response of the biomedical community 1,2 . However, novel vaccines and antivirals require time for development, thus repurposing of available drugs is a fast alternative and many attempts using different approaches are made [3][4][5][6] . Antiviral drugs are traditionally aimed at viral enzymes and are able to cure or reduce symptoms in several viral infections (HIV, HCV and HSV-1 7 ).…”

Amino acid interacting network in the receptor-binding domain of SARS-CoV-2 spike protein

“…This new concept and method of AABP for interaction between amino acids is clearly one step beyond the simpler interatomic interactions in proteins. 12 More importantly, the method can be readily applied to and play a crucial role in large-scale computation for protein design [34][35][36][37] and understanding the mutation process [38][39][40] leading to effective vaccine and therapeutic drug design [41][42][43] in combating COVID-19 pandemics. This is because such urgent research topics require the information on the details of the interaction under different environments, involving a single amino acid or clusters of multiple amino acids.…”

Screening of plant-based natural compounds as a potential COVID-19 main protease inhibitor: anin silicodocking and molecular dynamics simulation approach

“…Explicit solvent molecular dynamics (MD) simulations have been executed for the further investigation of virtual molecular docking results. GROMACS v.2019.4 package has been used to run 100 ns MD simulation of protease-ligand complexes according to the previously described method (Das et al, 2020;Panda et al, 2020). GROMOS96 43a1 in single point charge (SPC) water models (Berendsen et al, 1995) and PRODRG server (van Aalten et al, 1996) have been used to generate force field and parameter files for protease and ligands.…”