SARS-CoV-2 protein drug targets landscape: a potential pharmacological insight view for the new drug development

ABSTRACT

Introduction: Protein drug targets play a significant choice in different stages of the drug discovery process. There is an urgent need to understand the drug discovery approaches and protein drug targets (PDT) of SARS-CoV-2, with structural insights for the development of SARS-CoV-2 drugs through targeted therapeutic approach.

Areas covered: We have described the protein as a drug target class and also discussed various drug discovery approaches for SARS-CoV-2 involving the protein drug targets such as drug repurposing study, designing of viral entry inhibitors, viral replication inhibitors, and different enzymes of the virus. We have performed comprehensive literature search from the popular databases such as PubMed Google scholar, Web of Science, and Scopus. Finally, we have illustrated the structural landscape of different significant viral proteins (3 CLpro or Mpro, PLpro, RdRp, helicase, S protein) and host proteins as drug targets (cathepsin L, furin, TMPRSS2, ACE2).

Expert opinion: The structural landscape of PDT with their binding pockets, and significant residues involved in binding has been discussed further to better understand the PDT and the structure-based drug discovery for SARS-CoV-2. This attempt will increase more therapeutic options, and combination therapies with a multi-target strategy.

KEYWORDS:

• Protein drug target
• SARS-CoV-2: structural landscape
• viral protein target
• host protein target

Article highlights

• Understanding more about the protein drug targets will initiate the drug discovery process of SARS-CoV-2.

• We have performed comprehensive literature search from the different databases such as PubMed, Google Scholar, Web of Science and Scopus to understand the protein drug targets of SARS-CoV-2.

• In this paper, we describe the structural landscape of different significant viral proteins (3CLpro or Mpro, PLpro, RdRp, helicase, S protein) and host proteins as drug targets (cathepsin L, furin, TMPRSS2, ACE2). We also describe the interaction of novel drug candidates with these protein drug targets in the clinical pharmacology point of view.

• Different parameters of the structural landscape of protein drug targets are illustrated such as binding pockets, and significant residues involved in binding with drug-like molecules.

• This understanding will help in the process of structure-based drug discovery for SARS-CoV-2.

• Our attempt will increase more therapeutic options, and combination therapies of this disease with a multi-target strategy.

Declaration of interest

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.