Crosstalk Between Viral Envelop-E Protein and Host Innate Immune System: Exploring Pharmacological Targets and Agents

The Envelope (E)-protein is a key structural element of enveloped viruses that plays a significant role in host-pathogen interactions, viral growth, and hijacking of host innate immune system. Due to lack of antiviral agents and significant adverse effects and less affordability of vaccines, the E-protein targeted drug development is gaining critical attention among the researchers. The present review explores the structural and genomic diversities of E-protein among animal viruses with special interest to flaviviruses, coronaviruses, and herpesviruses. E-protein's viroporin activity damages host cell membrane and induces inflammation that advances the disease progression. The review also explains the viroporin-mediated NOD-like receptor family pyrin domain-containing 3 (NLRP3), Toll-like receptors (TLRs), nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs), and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-linked cellular mechanisms in virus-mediated inflammation. The E-protein is considered an alternative promising antiviral target as its functional domain is conserved. This review further enlists the natural, and synthetic inhibitors of E-protein in the development of antiviral agents based on computational, in vitro, and in vivo studies. The E-protein's universal conservation ability to fasten to cellular membranes and limited structural data imparts significant challenge to selective drug inhibition. The present review highlights that the E-protein together with multiple viral factors will boost treatment performance while minimising viral resistance. In addition, broad-range inhibitors targeting E-proteins have the potential to produce single treatment solutions in combating viral infections including several viral strains. In conclusion, E-protein targeted drug would be beneficial in developing potential antiviral agents with high drug specificity, and less viral resistance.