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

TLDR

SARS‑CoV‑2 causes rapidly spreading respiratory illness with multi‑organ failure, and pharmaceutical repurposing offers a faster, cheaper alternative to de novo drug discovery. The study aims to use immunoinformatics to identify T‑cell and B‑cell epitopes that could guide experimental vaccine development with higher reliability and fewer experiments. The authors performed virtual screening of antiviral compounds against the spike glycoprotein, main protease, and the RBD‑ACE2 complex of SARS‑CoV‑2. PC786, an antiviral polymerase inhibitor, binds with high affinity to the spike, main protease, and RBD‑ACE2 complex, and its interaction induces conformational changes in the postfusion trimeric S protein RBD.

Abstract

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 (Mpro), 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.